262 results on '"Miguel Angel Diaz"'
Search Results
2. Outcome of haematopoietic cell transplantation in children with lysosomal acid lipase deficiency: a study on behalf of the EBMT Inborn Errors Working Party
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Su Han Lum, Milen Minkov, Simon A. Jones, Sheree Hazelaar, Tiarlan Sirait, Jane E. Potter, Polina Stepensky, Frederic Garban, Herbert Pichler, Jerry Stein, Zuhre Kaya, Ansgar Schulz, Karin Mellgren, Cristina Diaz de Heredia, Cecile Pochon, Susana Riesco, Miguel Angel Diaz, Gérard Michel, Caroline Lindemans, Bernd Gruhn, Michael H. Albert, Arjan C. Lankester, Bénédicte Neven, and Robert Wynn
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Transplantation ,Hematology - Published
- 2023
3. The Impact of Pre-Transplant Extramedullary Disease on the Outcome of Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in Children- on Behalf of PDWP/EBMT
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Juliana Silva, Jacques-Emmanuel Galimard, Jean-Hugues Dalle, Franco Locatelli, Hawazen S. Alsaedi, Miguel Angel Diaz, Charlotte Jubert, Yves Bertrand, Giuseppina Simone, Peter Bader, Franca Fagioli, Vassiliki Kitra Roussou, Caroline Furness, Robert Wynn, Birgit Burkhardt, Alessandra Biffi, Marc Bierings, Cristina Díaz de Heredia, Arcangelo Prete, Amos Toren, Katharine Patrick, Wolfgang Holter, Arnaud Dalissier, Kanchan Rao, and Selim Corbacioglu
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Immunology ,Cell Biology ,Hematology ,Biochemistry - Published
- 2022
4. Association between the choice of the conditioning regimen and outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis
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Guru Subramanian Guru Murthy, Soyoung Kim, Noel Estrada-Merly, Muhammad Bilal Abid, Mahmoud Aljurf, Amer Assal, Talha Badar, Sherif M. Badawy, Karen Ballen, Amer Beitinjaneh, Jan Cerny, Saurabh Chhabra, Zachariah DeFilipp, Bhagirathbhai Dholaria, Miguel Angel Diaz Perez, Shatha Farhan, Cesar O. Freytes, Robert Peter Gale, Siddhartha Ganguly, Vikas Gupta, Michael R. Grunwald, Nada Hamad, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Tania Jain, Omer Jamy, Mark Juckett, Matt Kalaycio, Maxwell M. Krem, Hillard M Lazarus, Mark Litzow, Reinhold Munker, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Guillermo Ortí, Sagar S. Patel, Marjolein Van der Poel, David A. Rizzieri, Bipin N Savani, Sachiko Seo, Melhem Solh, Leo F. Verdonck, Baldeep Wirk, Jean A. Yared, Ryotaro Nakamura, Betul Oran, Bart Scott, Wael Saber, Institut Català de la Salut, [Murthy GSG] Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. [Kim S] Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA. CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. [Estrada-Merly N] CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. [Abid MB] Divisions of Hematology/Oncology and Infectious Diseases, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. [Aljurf M] Department of Oncology, King Faisal Specialist Hospital Center and Research, Riyadh, Saudi Arabia. [Assal A] Columbia University Irving Medical Center, Department of Medicine, Bone Marrow Transplant and Cell Therapy Program, New York, NY, USA. [Ortí G] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Al·loempelts ,Mielofibrosi ,Cèl·lules mare hematopoètiques - Trasplantació ,Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Hematopoietic Stem Cell Transplantation [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Hemic and Lymphatic Diseases::Hematologic Diseases::Bone Marrow Diseases::Myeloproliferative Disorders::Primary Myelofibrosis [DISEASES] ,intervenciones quirúrgicas::trasplante::trasplante de células::trasplante de células madre::trasplante de células madre hematopoyéticas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Surgical Procedures, Operative::Transplantation::Transplantation, Homologous [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,enfermedades hematológicas y linfáticas::enfermedades hematológicas::enfermedades de la médula ósea::trastornos mieloproliferativos::mielofibrosis primaria [ENFERMEDADES] ,Hematology ,intervenciones quirúrgicas::trasplante::trasplante homólogo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] - Abstract
Allogeneic hematopoietic; Cell transplantation; Myelofibrosis Trasplante alogénico; Células hematopoyéticas; Mielofibrosis Trasplantament al·logènic; Cèl·lules hematopoètiques; Mielofibrosi Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative treatment for myelofibrosis. However, the optimal conditioning regimen either with reduced-intensity conditioning (RIC) or myeloablative conditioning (MAC) is not well known. Using the Center for International Blood and Marrow Transplant Research database, we identified adults aged ≥18 years with myelofibrosis undergoing allo-HCT between 2008-2019 and analyzed the outcomes separately in the RIC and MAC cohorts based on the conditioning regimens used. Among 872 eligible patients, 493 underwent allo-HCT using RIC (fludarabine/ busulfan n=166, fludarabine/melphalan n=327) and 379 using MAC (fludarabine/busulfan n=247, busulfan/cyclophosphamide n=132). In multivariable analysis with RIC, fludarabine/melphalan was associated with inferior overall survival (hazard ratio [HR]=1.80; 95% confidenec interval [CI]: 1.15-2.81; P=0.009), higher early non-relapse mortality (HR=1.81; 95% CI: 1.12-2.91; P=0.01) and higher acute graft-versus-host disease (GvHD) (grade 2-4 HR=1.45; 95% CI: 1.03-2.03; P=0.03; grade 3-4 HR=2.21; 95%CI: 1.28-3.83; P=0.004) compared to fludarabine/busulfan. In the MAC setting, busulfan/cyclophosphamide was associated with a higher acute GvHD (grade 2-4 HR=2.33; 95% CI: 1.67-3.25; P
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- 2023
5. Clinical Characteristics and Outcomes of COVID-19 in Pediatric and Early Adolescent and Young Adult Hematopoietic Stem Cell Transplant Recipients: A Cohort Study
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Neel S. Bhatt, Akshay Sharma, Andrew St. Martin, Muhammad Bilal Abid, Valerie I. Brown, Miguel Angel Diaz Perez, Haydar Frangoul, Shahinaz M. Gadalla, Megan M. Herr, Maxwell M. Krem, Hillard M. Lazarus, Michael J. Martens, Parinda A. Mehta, Taiga Nishihori, Tim Prestidge, Michael A. Pulsipher, Hemalatha G. Rangarajan, Kirsten M. Williams, Lena E. Winestone, Dwight E. Yin, Marcie L. Riches, Christopher E. Dandoy, and Jeffery J. Auletta
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Pediatric ,Transplantation ,Pediatric Research Initiative ,Adolescent ,Early adolescent and young adult ,Prevention ,Hematopoietic Stem Cell Transplantation ,COVID-19 ,Cell Biology ,Hematology ,Stem Cell Research ,Regenerative Medicine ,Hematopoietic stem cell ,Oxygen ,Cohort Studies ,Young Adult ,COVID-19 Testing ,Good Health and Well Being ,Clinical Research ,Stem Cell Research - Nonembryonic - Human ,Molecular Medicine ,Immunology and Allergy ,Humans ,Child ,Cancer - Abstract
Adult hematopoietic stem cell transplantation (HSCT) recipients are at a high risk of adverse outcomes after COVID-19. Although children have had better outcomes after COVID-19 compared to adults, data on risk factors and outcomes of COVID-19 among pediatric HSCT recipients are lacking. We describe outcomes of HSCT recipients who were ≤21 years of age at COVID-19 diagnosis and were reported to the Center for International Blood and Marrow Transplant Research between March 27, 2020, and May 7, 2021. The primary outcome was overall survival after COVID-19 diagnosis. We determined risk factors of COVID-19 as a secondary outcome in a subset of allogeneic HSCT recipients. A total of 167 pediatric HSCT recipients (135 allogeneic; 32 autologous HSCT recipients) were included. Median time from HSCT to COVID-19 was 15 months (interquartile range [IQR] 7-45) for allogeneic HSCT recipients and 16 months (IQR 6-59) for autologous HSCT recipients. Median follow-up from COVID-19 diagnosis was 53 days (range 1-270) and 37 days (1-179) for allogeneic and autologous HSCT recipients, respectively. Although COVID-19 was mild in 87% (n=146/167), 10% (n=16/167) of patients required supplemental oxygen or mechanical ventilation. The 45-day overall survival was 95% (95% confidence interval [CI], 90-99) and 90% (74-99) for allogeneic and autologous HSCT recipients, respectively. Cox regression analysis showed that patients with a hematopoietic cell transplant comorbidity index (HCT-CI) score of 1-2 were more likely to be diagnosed with COVID-19 (hazard ratio 1.95; 95% CI, 1.03-3.69, P=.042) compared to those with an HCT-CI of 0. Pediatric and early adolescent and young adult HSCT recipients with pre-HSCT comorbidities were more likely to be diagnosed with COVID-19. Overall mortality, albeit higher than the reported general population estimates, was lower when compared with previously published data focusing on adult HSCT recipients.
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- 2022
6. Graft failure after 'ex-vivo' T-cell depleted haploidentical transplantation in pediatric patients with high-risk hematological malignancies. A risk factors and outcomes analysis
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Raquel Alenda, Blanca Molina, Ivan Lopez, Alba Pereto, Miguel Ángel Moreno, Josune Zubicaray, Julián Sevilla, Marta González-Vicent, Miguel Angel Diaz, Jose L. Vicario, and Ana Castillo
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Cancer Research ,medicine.medical_specialty ,Acute leukemia ,Graft failure ,Haploidentical transplantation ,business.industry ,T cell ,Outcome analysis ,Hematology ,Gastroenterology ,medicine.anatomical_structure ,Oncology ,Internal medicine ,medicine ,Cumulative incidence ,business ,CD8 ,Ex vivo - Abstract
Risk factors and outcomes of GF after TCD haploidentical transplantation in children with hematological malignancies were analyzed. 148 TCD transplants were included. 78 patients were diagnosed of ALL and 70 patients of AML. 22 out of 148 patients developed GF. MVA showed that patient
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- 2021
7. Adapting the HCT-CI Definitions for Children, Adolescents, and Young Adults with Hematologic Malignancies Undergoing Allogeneic Hematopoietic Cell Transplantation
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Brian D. Friend, Larisa Broglie, Brent R. Logan, Saurabh Chhabra, Caitrin Bupp, Gary Schiller, Amer Beitinjaneh, Miguel Angel Diaz Perez, Gregory M.T. Guilcher, Hasan Hashem, Gerhard C. Hildebrandt, Maxwell M. Krem, Hillard M. Lazarus, Taiga Nishihori, Roomi Nusrat, Seth J. Rotz, Baldeep Wirk, Matthew Wieduwilt, Marcelo Pasquini, Bipin N. Savani, Edward A. Stadtmauer, Mohamed L. Sorror, and Monica S. Thakar
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Abstract
Allogeneic hematopoietic cell transplantation is a curative procedure for hematologic malignancies but is associated with a significant risk of non-relapse mortality (NRM). The Hematopoietic Cell Transplantation- Comorbidity Index (HCT-CI) is a prognostic tool that discriminates this risk in all age groups. A recent survey of transplant physicians demonstrated that 79% of pediatric providers used the HCT-CI infrequently, and most reported concerns about its applicability in the younger population. We conducted a retrospective study using the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of expanded HCT-CI definitions on NRM in pediatric and young adult patients with hematologic malignancies. We included 5,790 patients40 years old receiving allogeneic transplant between 2008 and 2017 to examine broader definitions of comorbidities in the HCT-CI, including history of mechanical ventilation and fungal infection, estimated glomerular filtration rate (eGFR), and body mass index (BMI) percentiles. Multivariable Fine-Gray models were created to determine the effect of each HCT-CI defining comorbidity and its modification on NRM, and were utilized to develop two novel risk scores. We next developed the expanded HCT-CI for children and young adults (youth with malignancies; expanded ymHCT-CI), where 23% patients had an increased comorbidity score, compared to the HCT-CI. Comorbidities with hazard ratio (HR)1.2 were then removed to create the simplified HCT-CI for children and young adults (youth with malignancies; simplified ymHCT-CI), which demonstrated higher scores corresponded to a greater risk of NRM (p0.001). These novel comorbidity indices with broader definitions are more relevant to pediatric and young adult patients, and prospective studies are needed to validate these in the younger patient population. It remains to be seen if the development of these pediatric-specific and practical risk indices increases their utilization by the pediatric transplant community.
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- 2022
8. Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113 AML patients
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Boyiadzis, Michael, Zhang, Mei-Jie, Chen, Karen, Abdel-Azim, Hisham, Abid, Muhammad Bilal, Aljurf, Mahmoud, Bacher, Ulrike, Badar, Talha, Badawy, Sherif M, Battiwalla, Minoo, Bejanyan, Nelli, Bhatt, Vijaya Raj, Brown, Valerie I, Castillo, Paul, Cerny, Jan, Copelan, Edward A, Craddock, Charles, Dholaria, Bhagirathbhai, Perez, Miguel Angel Diaz, Ebens, Christen L, Gale, Robert Peter, Ganguly, Siddhartha, Gowda, Lohith, Grunwald, Michael R, Hashmi, Shahrukh, Hildebrandt, Gerhard C, Iqbal, Madiha, Jamy, Omer, Kharfan-Dabaja, Mohamed A, Khera, Nandita, Lazarus, Hillard M, Lin, Richard, Modi, Dipenkumar, Nathan, Sunita, Nishihori, Taiga, Patel, Sagar S, Pawarode, Attaphol, Sharma, Akshay, Solh, Melhem, Wagner, John L, Wang, Trent, Williams, Kirsten M, Winestone, Lena E, Wirk, Baldeep, Hourigan, Christopher S, Litzow, Mark, Kebriaei, Partow, de Lima, Marcos, Page, Kristin, and Weisdorf, Daniel J
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610 Medizin und Gesundheit - Abstract
We investigated the impact of the number of induction/consolidation cycles on outcomes of 3113 adult AML patients who received allogeneic hematopoietic cell transplantation (allo-HCT) between 2008 and 2019. Patients received allo-HCT using myeloablative (MAC) or reduced-intensity (RIC) conditioning in first complete remission (CR) or with primary induction failure (PIF). Patients who received MAC allo-HCT in CR after 1 induction cycle had 1.3-fold better overall survival (OS) than 2 cycles to CR and 1.47-fold better than ≥3 cycles. OS after CR in 2 or ≥3 cycles was similar. Relapse risk was 1.65-fold greater in patients receiving ≥3 cycles to achieve CR. After RIC allo-HCT, the number of induction cycles to CR did not affect OS. Compared to CR in 1 cycle, relapse risk was 1.24-1.41-fold greater in patients receiving 2 or ≥3 cycles. For patients receiving only 1 cycle to CR, consolidation therapy prior to MAC allo-HCT was associated with improved OS vs. no consolidation therapy. Detectable MRD at the time of MAC allo-HCT did not impact outcomes while detectable MRD preceding RIC allo-HCT was associated with an increased risk of relapse. For allo-HCT in PIF, OS was significantly worse than allo-HCT in CR after 1-3 cycles.
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- 2022
9. Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis
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Asad Bashey, Carolyn Mulroney, Roy F. Chemaly, Paul Castillo, Ephraim J. Fuchs, Christopher G. Kanakry, Hillard M. Lazarus, Hongtao Liu, Per Ljungman, Jeffery J. Auletta, Stefan O. Ciurea, Jennifer A. Kanakry, Miguel-Angel Perales, Muhammad Bilal Abid, Randy Taplitz, Rizwan Romee, Richard Masiarz, Soyoung Kim, Amer Beitinjaneh, Marcie L. Riches, Christopher E. Dandoy, Taiga Nishihori, Min Chen, Krishna V. Komanduri, Kristin Page, Sunita Nathan, Miguel Angel Diaz, Maxwell M. Krem, Scott R. Goldsmith, and Siddhartha Ganguly
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Transplantation ,medicine.medical_specialty ,Cyclophosphamide ,business.industry ,Incidence (epidemiology) ,Immunology ,Congenital cytomegalovirus infection ,Cytomegalovirus ,virus diseases ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,Cytomegalovirus infection ,Calcineurin ,Graft-versus-host disease ,Internal medicine ,Cytomegalovirus Infections ,Humans ,Medicine ,business ,Serostatus ,medicine.drug - Abstract
Prior studies suggest increased cytomegalovirus (CMV) infection after haploidentical donor transplantation with posttransplant cyclophosphamide (HaploCy). The role of allograft source and posttransplant cyclophosphamide (PTCy) in CMV infection is unclear. We analyzed the effect of graft source and PTCy on incidence of CMV infection, and effects of serostatus and CMV infection on transplant outcomes. We examined patients reported to the Center for International Blood and Marrow Transplantation Research between 2012 and 2017 who had received HaploCy (n = 757), matched related (Sib) with PTCy (SibCy, n = 403), or Sib with calcineurin inhibitor-based prophylaxis (SibCNI, n = 1605). Cumulative incidences of CMV infection by day 180 were 42%, 37%, and 23%, respectively (P < .001). CMV disease was statistically comparable. CMV infection risk was highest for CMV-seropositive recipients (R+), but significantly higher in PTCy recipients regardless of donor (HaploCy [n = 545]: hazard ratio [HR], 50.3; SibCy [n = 279]: HR, 47.7; SibCNI [n = 1065]: HR, 24.4; P < .001). D+/R− patients also had increased risk for CMV infection. Among R+ or those developing CMV infection, HaploCy had worse overall survival and nonrelapse mortality. Relapse was unaffected by CMV infection or serostatus. PTCy was associated with lower chronic graft-versus-host disease (GVHD) overall, but CMV infection in PTCy recipients was associated with higher chronic GVHD (P = .006). PTCy, regardless of donor, is associated with higher incidence of CMV infection, augmenting the risk of seropositivity. Additionally, CMV infection may negate the chronic GVHD protection of PTCy. This study supports aggressive prevention strategies in all receiving PTCy.
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- 2021
10. Neighborhood poverty and pediatric allogeneic hematopoietic cell transplantation outcomes: a CIBMTR analysis
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C. Fred LeMaistre, Minoo Battiwalla, Amir Steinberg, Wael Saber, Biju George, Siddhartha Ganguly, Theresa Hahn, Navneet S. Majhail, Naya He, Cesar O. Freytes, Staci D. Arnold, Jennifer M. Knight, Sachiko Seo, Ruta Brazauskas, Rammurti T. Kamble, Leslie Lehmann, Richard F. Olsson, Mahmoud Aljurf, Shahrukh K. Hashmi, Miguel Angel Diaz, Alok Srivastava, Christopher E. Dandoy, Hillard M. Lazarus, Jason Law, Nandita Khera, Baldeep Wirk, Ayami Yoshimi, Haydar Frangoul, Akshay Sharma, Neel S. Bhatt, Raquel M. Schears, David Szwajcer, Jaime M. Preussler, Ibrahim Ahmed, David Gómez-Almaguer, William A. Wood, Christine Duncan, Bipin N. Savani, Sherif M. Badawy, A. Samer Al-Homsi, Kira Bona, Jignesh Dalal, Hisham Abdel-Azim, and Sara Beattie
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Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Databases, Factual ,Social Determinants of Health ,Immunology ,Psychological intervention ,MEDLINE ,Graft vs Host Disease ,Disease ,Infections ,Biochemistry ,Insurance Coverage ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Cause of Death ,Neoplasms ,030225 pediatrics ,Humans ,Transplantation, Homologous ,Medicine ,Social determinants of health ,Child ,Poverty ,Hematopoietic cell ,Medicaid ,business.industry ,Hematopoietic Stem Cell Transplantation ,Infant ,Cell Biology ,Hematology ,Survival Analysis ,United States ,Transplantation ,Treatment Outcome ,surgical procedures, operative ,Child, Preschool ,030220 oncology & carcinogenesis ,Chronic Disease ,Female ,Erratum ,business ,Follow-Up Studies - Abstract
Social determinants of health, including poverty, contribute significantly to health outcomes in the United States; however, their impact on pediatric hematopoietic cell transplantation (HCT) outcomes is poorly understood. We aimed to identify the association between neighborhood poverty and HCT outcomes for pediatric allogeneic HCT recipients in the Center for International Blood and Marrow Transplant Research database. We assembled 2 pediatric cohorts undergoing first allogeneic HCT from 2006 to 2015 at age ≤18 years, including 2053 children with malignant disease and 1696 children with nonmalignant disease. Neighborhood poverty exposure was defined a priori per the US Census definition as living in a high-poverty ZIP code (≥20% of persons below 100% federal poverty level) and used as the primary predictor in all analyses. Our primary outcome was overall survival (OS), defined as the time from HCT until death resulting from any cause. Secondary outcomes included relapse and transplantation-related mortality (TRM) in malignant disease, acute and chronic graft-versus-host disease, and infection in the first 100 days post-HCT. Among children undergoing transplantation for nonmalignant disease, neighborhood poverty was not associated with any HCT outcome. Among children undergoing transplantation for malignant disease, neighborhood poverty conferred an increased risk of TRM but was not associated with inferior OS or any other transplantation outcome. Among children with malignant disease, a key secondary finding was that children with Medicaid insurance experienced inferior OS and increased TRM compared with those with private insurance. These data suggest opportunities for future investigation of the effects of household-level poverty exposure on HCT outcomes in pediatric malignant disease to inform care delivery interventions.
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- 2021
11. Correction to: Impact of pre-transplant induction and consolidation cycles on AML allogeneic transplant outcomes: a CIBMTR analysis in 3113AML patients
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Boyiadzis, Michael, Zhang, Mei-Jie, Chen, Karen, Abdel-Azim, Hisham, Abid, Muhammad Bilal, Aljurf, Mahmoud, Bacher, Ulrike, Badar, Talha, Badawy, Sherif M, Battiwalla, Minoo, Bejanyan, Nelli, Bhatt, Vijaya Raj, Brown, Valerie I, Castillo, Paul, Cerny, Jan, Copelan, Edward A, Craddock, Charles, Dholaria, Bhagirathbhai, Perez, Miguel Angel Diaz, Ebens, Christen L, Gale, Robert Peter, Ganguly, Siddhartha, Gowda, Lohith, Grunwald, Michael R, Hashmi, Shahrukh, Hildebrandt, Gerhard C, Iqbal, Madiha, Jamy, Omer, Kharfan-Dabaja, Mohamed A, Khera, Nandita, Lazarus, Hillard M, Lin, Richard, Modi, Dipenkumar, Nathan, Sunita, Nishihori, Taiga, Patel, Sagar S, Pawarode, Attaphol, Saber, Wael, Sharma, Akshay, Solh, Melhem, Wagner, John L, Wang, Trent, Williams, Kirsten M, Winestone, Lena E, Wirk, Baldeep, Zeidan, Amer, Hourigan, Christopher S, Litzow, Mark, Kebriaei, Partow, de Lima, Marcos, Page, Kristin, and Weisdorf, Daniel J
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Cancer Research ,Oncology ,Hematology ,610 Medicine & health - Published
- 2023
12. Expanded HCT-CI Definitions Capture Comorbidity Better for Younger Patients of Allogeneic HCT for Nonmalignant Diseases
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Larisa Broglie, Brian D. Friend, Saurabh Chhabra, Brent R. Logan, Caitrin Bupp, Gary Schiller, Bipin N. Savani, Edward Stadtmauer, Allistair A. Abraham, Mahmoud Aljurf, Sherif M. Badawy, Miguel Angel Diaz Perez, Eva C. Guinan, Hasan Hashem, Maxwell M. Krem, Hillard M. Lazarus, Seth J. Rotz, Baldeep Wirk, Jean A. Yared, Marcelo Pasquini, Monica S. Thakar, and Mohamed L. Sorror
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Transplantation ,Molecular Medicine ,Immunology and Allergy ,Cell Biology ,Hematology - Abstract
Allogeneic hematopoietic cell transplantation (HCT) can cure many nonmalignant conditions, but concern for morbidity and mortality remains. To help physicians estimate patient-specific transplant mortality risk, the HCT comorbidity index (HCT-CI) is used. However, pediatric physicians use the HCT-CI less frequently than adult counterparts. We used the Center for International Blood and Marrow Transplant Research database to expand the HCT-CI comorbidity definitions to be more inclusive of children and adolescent and young adult (AYA) patients, adding history of mechanical ventilation, history of invasive fungal infection, assessment of chronic kidney disease (CKD) by estimated glomerular filtration rate, expanding the definition of obesity, and adding an underweight category. A total of 2815 children and AYAs (40 years old) who received first allogeneic HCT for nonmalignant diseases from 2008 to 2017 were included to create an expanded youth nonmalignant HCT-CI (expanded ynHCT-CI) and a simplified non-malignant (simplified ynHCT-CI) HCT-CI. The expanded comorbidities occurred frequently-history of mechanical ventilation (9.6%), history of invasive fungal infection (5.9%), mild CKD (12.2%), moderate/severe CKD (2.1%), obesity (10.9%), and underweight (14.5%). Thirty-nine percent of patients had an increase in their comorbidity score using the expanded ynHCT-CI, leading to a redistribution of scores: ynHCT-CI score 0 (35%), 1-2 (36.4%), and ≥3 (28.6%). Patients with an increase in their comorbidity score had an increased hazard of mortality compared to those whose score remained the same (hazard ratio = 1.41; 95% confidence interval, 1.01-1.98). Modifications to the HCT-CI can benefit children and AYA patients with nonmalignant diseases, creating a risk assessment tool that is clinically relevant and better captures comorbidity in this younger population.
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- 2023
13. Community health status and outcomes after allogeneic hematopoietic cell transplantation in the United States
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Alois Gratwohl, Jason Law, David Szwajcer, Jean A. Yared, Bronwen E. Shaw, Ruta Brazauskas, Amer Beitinjaneh, Matthew L. Ulrickson, Hisham Abdel-Azim, Sara Beattie, Navneet S. Majhail, Shahrukh K. Hashmi, J. Douglas Rizzo, Wael Saber, Neel S. Bhatt, William A. Wood, Charles F. LeMaistre, Stephanie J. Lee, Bipin N. Savani, Sherif M. Badawy, Stefan O. Ciurea, Richard F. Olsson, David A. Rizzieri, Hasan Hashem, Sachiko Seo, Sanghee Hong, Jan Cerny, Akshay Sharma, Kyle Hebert, Hélène Schoemans, Hillard M. Lazarus, Ayami Yoshimi, Rammurti T. Kamble, Siddhartha Ganguly, Nosha Farhadfar, Theresa Hahn, Miguel Angel Diaz, Nandita Khera, Mahmoud Aljurf, and Usama Gergis
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Male ,Cancer Research ,0302 clinical medicine ,Risk Factors ,80 and over ,Medicine ,030212 general & internal medicine ,Cancer ,Aged, 80 and over ,community health ,Framingham Risk Score ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,allogeneic transplant ,Treatment Outcome ,Local ,Oncology ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Community health ,Public Health and Health Services ,Female ,Public Health ,Homologous ,Adult ,medicine.medical_specialty ,Adolescent ,Oncology and Carcinogenesis ,survival ,Community Health Planning ,Article ,Young Adult ,03 medical and health sciences ,Clinical Research ,Internal medicine ,Transplantation, Homologous ,Humans ,Nonrelapse mortality ,hematopoietic cell transplantation ,Oncology & Carcinogenesis ,Aged ,Transplantation ,Hematopoietic cell ,business.industry ,Prevention ,United States ,Neoplasm Recurrence ,Good Health and Well Being ,Increased risk ,Bone transplantation ,Neoplasm Recurrence, Local ,business - Abstract
Background The association of community factors and outcomes after hematopoietic cell transplantation (HCT) has not been comprehensively described. Using the County Health Rankings and Roadmaps (CHRR) and the Center for International Blood and Marrow Transplant Research (CIBMTR), this study evaluated the impact of community health status on allogeneic HCT outcomes. Methods This study included 18,544 adult allogeneic HCT recipients reported to the CIBMTR by 170 US centers in 2014-2016. Sociodemographic, environmental, and community indicators were derived from the CHRR, an aggregate community risk score was created, and scores were assigned to each patient (patient community risk score [PCS]) and transplant center (center community risk score [CCS]). Higher scores indicated less healthy communities. The impact of PCS and CCS on patient outcomes after allogeneic HCT was studied. Results The median age was 55 years (range, 18-83 years). The median PCS was -0.21 (range, -1.37 to 2.10; standard deviation [SD], 0.42), and the median CCS was -0.13 (range, -1.04 to 0.96; SD, 0.40). In multivariable analyses, a higher PCS was associated with inferior survival (hazard ratio [HR] per 1 SD increase, 1.04; 99% CI, 1.00-1.08; P = .0089). Among hematologic malignancies, a tendency toward inferior survival was observed with a higher PCS (HR, 1.04; 99% CI, 1.00-1.08; P = .0102); a higher PCS was associated with higher nonrelapse mortality (NRM; HR, 1.08; 99% CI, 1.02-1.15; P = .0004). CCS was not significantly associated with survival, relapse, or NRM. Conclusions Patients residing in counties with a worse community health status have inferior survival as a result of an increased risk of NRM after allogeneic HCT. There was no association between the community health status of the transplant center location and allogeneic HCT outcomes.
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- 2020
14. Plerixafor‐based mobilization in pediatric healthy donors with unfavorable donor/recipient body weight ratio resulted in a better <scp>CD34</scp> + collection yield: A retrospective analysis
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Manuel Ramírez, Marta González-Vicent, Josune Zubicaray, Elena Sebastián, Blanca Molina, Ana Castillo, Miguel Angel Diaz, Luis Madero, Eva M. Galvez, and Julián Sevilla
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medicine.medical_specialty ,Mobilization ,business.industry ,Plerixafor ,CD34 ,Urology ,Hematology ,General Medicine ,030204 cardiovascular system & hematology ,Body weight ,Transplantation ,03 medical and health sciences ,0302 clinical medicine ,Apheresis ,Cell dose ,medicine ,Retrospective analysis ,business ,030215 immunology ,medicine.drug - Abstract
INTRODUCTION In order to propose risk-adapted mobilization algorithms, several authors have tried to look for predictive factors of the CD34+ yield in healthy pediatric donors. Donor recipient body weight ratio (D/R ratio) was identified as one of the main variables related with the success to achieve the target cell dose for transplantation. According to this variable we modified the mobilization schedule. MATERIAL AND METHODS We report the results of 46 mobilizations and apheresis procedures performed in our center with unfavorable D/R ratio. Mobilization was attempted by the standard regime of G-CSF (10 mcg/kg/24 hours) in 28 cases (60.9%), with high dose G-CSF (10 mcg/kg/12 hours) in 9 cases (19.6%), and with plerixafor and G-CSF single dose regime in 9 cases (19.6%). RESULTS CD34+ cell quantification before apheresis is closely related to CD34+ yield, being the only factor related to collected CD34+ cells (beta .71; P
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- 2020
15. Relapse and Disease-Free Survival in Patients With Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Using Older Matched Sibling Donors vs Younger Matched Unrelated Donors
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Guru Subramanian Guru Murthy, Soyoung Kim, Zhen-Huan Hu, Noel Estrada-Merly, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Sherif M. Badawy, Amer Beitinjaneh, Chris Bredeson, Jean-Yves Cahn, Jan Cerny, Miguel Angel Diaz Perez, Nosha Farhadfar, Robert Peter Gale, Siddhartha Ganguly, Usama Gergis, Gerhard C. Hildebrandt, Michael R. Grunwald, Shahrukh Hashmi, Nasheed M. Hossain, Matt Kalaycio, Rammurti T. Kamble, Mohamed A. Kharfan-Dabaja, Betty Ky Hamilton, Hillard M. Lazarus, Jane Liesveld, Mark Litzow, David I. Marks, Hemant S. Murthy, Sunita Nathan, Aziz Nazha, Taiga Nishihori, Sagar S. Patel, Attaphol Pawarode, David Rizzieri, Bipin Savani, Sachiko Seo, Melhem Solh, Celalettin Ustun, Marjolein van der Poel, Leo F. Verdonck, Ravi Vij, Baldeep Wirk, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, and MUMC+: MA Hematologie (9)
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Adult ,Male ,Cancer Research ,Transplantation Conditioning ,BLOOD ,IMPACT ,BONE-MARROW ,Graft vs Host Disease ,ACUTE MYELOID-LEUKEMIA ,Disease-Free Survival ,Cohort Studies ,AGE ,Humans ,610 Medicine & health ,Aged ,Retrospective Studies ,Original Investigation ,Siblings ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,STEM ,RECIPIENTS ,Oncology ,Myelodysplastic Syndromes ,Neoplasm Recurrence, Local ,Unrelated Donors ,SYSTEM - Abstract
Importance Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. Objective To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. Design, Setting, and Participants This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. Interventions/Exposures Allo-HCT from an older MSD (donor age ���50 years) or a younger MUD (donor age ���35 years). Main Outcomes and Measures The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. Results Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P���=���.02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P���=���.07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P���
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- 2022
16. Corrosion risk assessment methodology by desalinated water supply in drinking water networks
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Miguel Angel Diaz Hurtado, Sara Espinosa, David Aguilera, Susana González, Manuel Argamasilla, and Alicia Piñero
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- 2022
17. Correction to: An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis
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Antonio M. Jimenez Jimenez, Marcos De Lima, Krishna V. Komanduri, Trent P. Wang, Mei-Jie Zhang, Karen Chen, Hisham Abdel-Azim, Muhammad Bilal Abid, Mahmoud Aljurf, Hassan Alkhateeb, Amer Assal, Ulrike Bacher, Frédéric Baron, Minoo Battiwalla, Amer Beitinjaneh, Nelli Bejanyan, Vijaya Raj Bhatt, Michael Byrne, Jean-Yves Cahn, Mitchell Cairo, Paul Castillo, Edward Copelan, Zachariah DeFilipp, Miguel Angel Diaz Perez, Mahmoud Elsawy, Robert Peter Gale, Biju George, Michael R. Grunwald, Gerhard C. Hildebrandt, William J. Hogan, Christopher G. Kanakry, Ankit Kansagra, Mohamed A. Kharfan-Dabaja, Nandita Khera, Maxwell M. Krem, Aleksandr Lazaryan, Joseph Maakaron, Rodrigo Martino, Joseph McGuirk, Fotios V. Michelis, Giuseppe Milone, Asmita Mishra, Hemant S. Murthy, Alberto Mussetti, Sunita Nathan, Taiga Nishihori, Richard F. Olsson, Neil Palmisiano, Sagar Patel, Ayman Saad, Sachiko Seo, Akshay Sharma, Melhem Solh, Leo F. Verdonck, Baldeep Wirk, Jean A. Yared, Mark Litzow, Partow Kebriaei, Christopher S. Hourigan, Wael Saber, and Daniel Weisdorf
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Transplantation ,Hematology ,610 Medicine & health - Published
- 2022
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18. HEV infection in stem cell transplant recipients-retrospective study of EBMT Infectious Diseases Working Party
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Nicole M. A. Blijlevens, Diana Averbuch, Hervé Ghesquières, Christian Koenecke, Rafael de la Cámara, Marc Bierings, José Luis Piñana, Miguel Angel Diaz, Nicolaus Kröger, Malgorzata Mikulska, Jakob Passweg, Nina Knelange, Hélène Labussière-Wallet, Olaf Penack, Lotus Wendel, Jan Styczyński, Anke H W Bruns, Antonia Sampol, Jan J. Cornelissen, and Hematology
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medicine.medical_specialty ,medicine.medical_treatment ,viruses ,Communicable Diseases ,chemistry.chemical_compound ,Immunocompromised Host ,SDG 3 - Good Health and Well-being ,Internal medicine ,Ribavirin ,Hepatitis E virus ,Medicine ,Humans ,Cause of death ,Retrospective Studies ,Hepatitis ,Transplantation ,business.industry ,virus diseases ,Retrospective cohort study ,Immunosuppression ,Hematology ,medicine.disease ,Transplant Recipients ,digestive system diseases ,Chronic infection ,Late diagnosis ,chemistry ,RNA ,Stem cell ,business ,Stem Cell Transplantation ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] - Abstract
Item does not contain fulltext HEV infection is an emerging cause of acute and chronic hepatitis in stem cell transplant (SCT) recipients. We performed a retrospective observational study among EBMT centers with the aim of describing characteristics, management and outcome of HEV after SCT. There were 34 cases of HEV infection from 12 centers in 6 countries, diagnosed in median 4.5 months after SCT; 20 of acute and 14 of chronic infection. Non-hepatic findings possibly associated with HEV infection were present in 9 (26%). Patients with chronic infection had more characteristics associated with severely immunocompromised status. Ribavirin was provided to 16 patients (47%; 40% with acute and 57% with chronic infection), in median for 75 days. Three (19%) patients discontinued it due to side effects. HEV-RNA clearance occurred in 29 patients (85%; 85% in acute and 86% in chronic infection). HEV was considered a cause of death in 3 (9%), with 2 cases with late diagnosis. Reduction of immunosuppression in those receiving it, and ribavirin treatment in those with chronic infection were associated with shorter time to HEV-RNA clearance. Policy on HEV testing varied between the centers. In conclusion, acute and chronic HEV hepatitis should be promptly diagnosed and managed in SCT recipients.
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- 2022
19. Clinical Features and Outcomes Associated with Bronchial Asthma Among COVID-19 Hospitalized Patients
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Miguel Angel Diaz, Nelly Catalan-Caceres, Thais C Beauperthuy, Carlos Domingo, Ethel Ibañez, Carmen Morata, and Alfredo De Diego
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Pulmonary and Respiratory Medicine ,Journal of Asthma and Allergy ,Immunology and Allergy - Abstract
Miguel Angel Diaz,1 Nelly Catalan-Caceres,1 Thais C Beauperthuy,2 Carlos Domingo,1 Ethel Ibañez,1 Carmen Morata,3 Alfredo De Diego2 1Allergy Department, Hospital Universitari I Politècnic La Fe, Valencia, Spain; 2Respiratory Department, Hospital Universitari I Politècnic La Fe, Valencia, Spain; 3Internal Medicine Department, Hospital Universitari I Politècnic La Fe, Valencia, SpainCorrespondence: Miguel Angel Diaz, Allergy Department, Hospital Universitari I Politècnic La Fe, Avinguda de Fernando Abril Martorell, 106, Valencia, 46026, Spain, Tel +34 961244084, Email diaz_mig@gva.esBackground: The impact of diagnosis treatment and bronchial asthma on coronavirus disease 2019 (COVID-19) associated outcomes remains unclear.Objective: To identify the prevalence and outcomes associated with asthma among hospitalized patients with COVID-19.Methods: Electronic health records of 130 patients with asthma among hospitalized patients with COVID-19 were reviewed. Two subgroups of asthmatic patients were compared according to clinical outcomes during hospitalization. Patients with death results, intubation, and/or need of intensive care unit (ICU) stay were grouped as asthmatic patients with severe COVID-19 outcomes, and the rest were grouped as asthmatic patients with non-severe COVID-19 outcomes. Multivariable analyses were conducted with logistic regression to identify independent risk factors for severe outcomes.Results: The prevalence of asthma in COVID-19 hospitalized patients was 5%. The mean age was 59.4 years and 54% were women. 17% received treatment in GINA step 4â 5 asthma at the time of admission. An allergic asthma phenotype was determined in 38%. There was no significant difference in hospital length of stay or need for intubation between asthmatic patients and global COVID-19 admitted patients. 17% of asthmatic patients developed a severe outcome, and 5% had a death result. Elevated Lactate Dehydrogenase (LDH) level, low transcutaneous pulse oximetry (SpO2), the coexistence of atrial fibrillation (AF), and need for moderate or high ICS at admission were independent risk factors for a worse outcome in asthmatics COVID-19 hospitalized patients.Conclusion: The prevalence of asthma in COVID-19 hospitalized patients was 5%, consistent with the asthma prevalence in the general population. The asthmatic patients with the previous prescription of moderate or high doses of ICS and/or coexistence of atrial fibrillation at admission had a higher risk of the severe outcome.Keywords: bronchial asthma, COVID-19, risk factors, outcomes
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- 2022
20. The mutational landscape in chronic myelomonocytic leukemia and its impact on allogeneic hematopoietic cell transplantation outcomes: a Center for Blood and Marrow Transplantation Research (CIBMTR) analysis
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Matthew Mei, Raju Pillai, Soyoung Kim, Noel Estrada-Merly, Michelle Afkhami, Lixin Yang, Zhuo Meng, Muhammad Bilal Abid, Mahmoud Aljurf, Ulrike Bacher, Amer Beitinjaneh, Christopher Bredeson, Jean-Yves Cahn, Jan Cerny, Edward Copelan, Corey Cutler, Zachariah DeFilipp, Miguel Angel Diaz Perez, Nosha Farhadfar, César O. Freytes, Shahinaz M. Gadalla, Siddhartha Ganguly, Robert Peter Gale, Usama Gergis, Michael R. Grunwald, Betty K. Hamilton, Shahrukh Hashmi, Gerhard C. Hildebrandt, Hillard M. Lazarus, Mark Litzow, Reinhold Munker, Hemant S. Murthy, Sunita Nathan, Taiga Nishihori, Sagar S. Patel, David Rizzieri, Sachiko Seo, Mithun Vinod Shah, Melhem Solh, Leo F. Verdonck, Ravi Vij, Ronald M. Sobecks, Betul Oran, Bart L. Scott, Wael Saber, and Ryotaro Nakamura
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Hematology ,610 Medicine & health - Abstract
Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of intermediate-2 (HR=1.46, P=0.049) or high (HR=3.22, P=0.0004) correlated significantly with overall survival. When the molecularly informed CPSS-Mol prognostic model was applied, a high CPSS-Mol score (HR=2 P=0.0079) correlated significantly with overall survival. The most common somatic mutations were in ASXL1 (62%), TET2 (35%), KRAS/NRAS (33% combined), and SRSF2 (31%). DNMT3A and TP53 mutations were associated with decreased overall survival (HR=1.70 [95% CI: 1.11-2.60], P=0.0147 and HR=2.72 [95% CI: 1.37-5.39], P=0.0042, respectively) while DNMT3A, JAK2, and TP53 mutations were associated with decreased disease-free survival (HR=1.66 [95% CI: 1.11-2.49], P=0.0138, HR=1.79 [95% CI: 1.06-3.03], P=0.0293, and HR=2.94 [95% CI: 1.50-5.79], P=0.0018, respectively). The only mutation associated with increased relapse was TP53 (HR=2.94, P=0.0201). Nonetheless, the impact of TP53 mutations specifically should be interpreted cautiously given their rarity in CMML. We calculated the goodness of fit measured by Harrell’s C-index for both the CPSS and CPSS-Mol, which were very similar. In summary, via registry data we have determined the mutational landscape in patients with CMML who underwent allogeneic HCT, and demonstrated an association between CPSS-Mol and transplant outcomes although without major improvement in the risk prediction beyond that provided by the CPSS.
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- 2022
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21. Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens: a CIBMTR report
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Michael Byrne, Jane L. Liesveld, Richard F. Olsson, Sagar S. Patel, Hongtao Liu, Eric Wong, Brenda M. Sandmaier, Bipin N. Savani, Hannah Choe, Partow Kebriaei, Gulrayz Ahmed, Tania Jain, Moussab Damlaj, Rebecca L. Olin, Mehdi Hamadani, Uday R. Popat, Neil Palmisiano, Rajneesh Nath, Mei-Jie Zhang, Mark R. Litzow, Attaphol Pawarode, Mark P. Hertzberg, Taiga Nishihori, Arnon Nagler, Jean A. Yared, Mitchell S. Cairo, Ioannis Politikos, Michael R. Grunwald, Hisham Abdel-Azim, Usama Gergis, David A. Rizzieri, Baldeep Wirk, Ashish Bajel, Rammurti T. Kamble, Hemant S. Murthy, Jean-Yves Cahn, Corey Cutler, Mahmoud Aljurf, A. Samer Al-Homsi, Geoffrey L. Uy, Miguel-Angel Perales, Muhammad Waqas Khan, Miguel Angel Diaz, Minocher Battiwalla, Mohamed A. Kharfan-Dabaja, Nosha Farhadfar, Natasha Kekre, Vaibhav Agrawal, Hillard M. Lazarus, Jan Cerny, Rodrigo Martino, Nandita Khera, Youjin Wang, Asmita Mishra, Nasheed Hossain, Luis Isola, Leo F. Verdonck, Nirav N. Shah, Vijaya Raj Bhatt, Zachariah DeFilipp, Daniel J. Weisdorf, Vikram Mathews, Edward A. Copelan, Aaron T. Gerds, C. Esar O. Freytes, David Valc A. Arcel, Shahrukh K. Hashmi, Mrinal M. Patnaik, Sunita Nathan, Sachiko Seo, Marcos de Lima, Qaiser Bashir, David I. Marks, Zheng Zhou, Yoshihiro Inamoto, Ryotaro Nakamura, Hai-Lin Wang, Edmund K. Waller, James M. Foran, Gerhard C. Hildebrandt, Amer Assal, Zartash Gul, Hassan B. Alkhateeb, Ulrike Bacher, and Wael Saber
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Adult ,Melphalan ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Gastroenterology ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,610 Medicine & health ,Busulfan ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Total body irradiation ,medicine.disease ,Fludarabine ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,Alemtuzumab ,Erratum ,business ,medicine.drug - Abstract
There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
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- 2020
22. Collection of Peripheral Blood Progenitor Cells in 1 Day Is Associated with Decreased Donor Toxicity Compared to 2 Days in Unrelated Donors
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Miguel Angel Diaz, Jane L. Liesveld, Ibrahim Ahmed, Jack W. Hsu, Raquel M. Schears, Hillard M. Lazarus, Sachiko Seo, Michael A. Pulsipher, Hemant S. Murthy, Richard F. Olsson, Gregory A. Hale, Soyoung Kim, Siddhartha Ganguly, John R. Wingard, Peiman Hematti, Dennis L. Confer, Galen E. Switzer, Thomas R. Spitzer, Amir Steinberg, Phyllis I. Warkentin, Kimberly A. Kasow, Nirali N. Shah, Jennifer A. Sees, Rammurti T. Kamble, Brent R. Logan, Bronwen E. Shaw, Michele W. Sugrue, Bipin N. Savani, Melhern Solh, Paulo N. Anderlini, Saurabh Chhabra, Christopher E. Dandoy, Nosha Farhadfar, Muneer H. Abidi, Christopher Bredeson, and Usama Gergis
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Transplantation ,medicine.medical_specialty ,Hematology ,business.industry ,Physiology ,Bone Marrow Stem Cell ,Filgrastim ,Apheresis ,Unrelated Donor ,Internal medicine ,Toxicity ,Medicine ,Progenitor cell ,business ,medicine.drug - Abstract
Peripheral blood stem cells (PBSCs) have been increasingly used for allogeneic hematopoietic cell transplantation instead of bone marrow stem cells. Current National Marrow Donor Program policy recommends 5 days of daily filgrastim, followed by either 1 or 2 days of apheresis for unrelated donors, depending on collection center choice. To date, there are no published studies comparing the differences in donor experience between 1 day and 2 days of apheresis. We examined 22,348 adult unrelated donor collections in 184 centers between 2006 and 2016. Of these 22,348 donors, 20,004 (89.5%) had collection on 1 day, and the other 2344 (9.5%) had collection over 2 days. Information on why donors underwent apheresis in 1 day or 2 days was not available. Donors who underwent apheresis in 1 day were more likely to be male (67% versus 46%; P 30, 30% versus 22%; P
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- 2020
23. Incidence, Risk Factors for and Outcomes of Transplant‐Associated Thrombotic Microangiopathy
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Narendranath Epperla, Ang Li, Brent Logan, Caitrin Fretham, Saurabh Chhabra, Mahmoud Aljurf, Lynette Chee, Edward Copelan, César O. Freytes, Peiman Hematti, Hillard M. Lazarus, Mark Litzow, Taiga Nishihori, Richard F. Olsson, Tim Prestidge, Wael Saber, Baldeep Wirk, Jean A. Yared, Alison Loren, Marcelo Pasquini, Allistair A. Abraham, Vaibhav Agrawal, Medhat Askar, Pere Barba, Alice Bertaina, Jean‐Yves Cahn, Jan Cerny, Hannah K. Choe, Miguel Angel Diaz, Christopher Dvorak, Nosha Farhadfar, Shahinaz M. Gadalla, Usama Gergis, Siddhartha Ganguly, Shahrukh Hashmi, Kimberly A. Kasow, Sunita Nathan, Roomi Nusrat, Sachiko Seo, and Niketa C. Shah
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Adult ,Male ,medicine.medical_specialty ,Thrombotic microangiopathy ,Adolescent ,medicine.medical_treatment ,Twins ,Hematopoietic stem cell transplantation ,urologic and male genital diseases ,Disease-Free Survival ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Risk Factors ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Renal replacement therapy ,Child ,Survival rate ,Aged ,Aged, 80 and over ,Thrombotic Microangiopathies ,business.industry ,Incidence ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Infant ,Hematology ,Middle Aged ,Allografts ,medicine.disease ,female genital diseases and pregnancy complications ,Renal Replacement Therapy ,Survival Rate ,surgical procedures, operative ,Child, Preschool ,030220 oncology & carcinogenesis ,Sirolimus ,Female ,Unrelated Donors ,Complication ,business ,030215 immunology ,medicine.drug - Abstract
Transplant-associated thrombotic microangiopathy (TA-TMA) is a complication of allogeneic transplantation (allo-HCT). The incidence and risk factors associated with TA-TMA are not well known. A retrospective analysis from the Center for International Blood and Marrow Transplant Research (CIBMTR) was conducted including patients receiving allo-HCT between 2008 and 2016, with the primary objective of evaluating the incidence of TA-TMA. Secondary objectives included identification of risk factors associated with TA-TMA, and the impact of TA-TMA on overall survival and the need for renal replacement therapy (RRT). Among 23,665 allo-HCT recipients, the 3-year cumulative incidence of TA-TMA was 3%. Variables independently-associated with increased incidence of TA-TMA included female sex, prior autologous transplant, primary disease (acute lymphoblastic leukaemia and severe aplastic anaemia), donor type (mismatched or unrelated donor), conditioning intensity (myeloablative), GVHD prophylaxis (sirolimus + calcineurin inhibitor), pre-transplant kidney dysfunction and acute GVHD (time-varying effect). TA-TMA was associated with higher mortality (HR = 3·1, 95% Confidence Interval [CI] = 2·8-16·3) and RRT requirement (HR = 7·1, 95% CI = 5·7-311·6). This study provides epidemiologic data on TA-TMA and its impact on transplant outcomes. Increased awareness of the risk factors will enable providers to be vigilant of this uncommon but serious transplant complication. The results will also provide benchmarking for future study designs and comparisons.
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- 2020
24. Predictors of Loss to Follow-Up Among Pediatric and Adult Hematopoietic Cell Transplantation Survivors
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Rammurti T. Kamble, Anita D'Souza, Leslie Lehmann, Kirk R. Schultz, Miguel Angel Diaz, Nandita Khera, Anita J. Kumar, Karen K. Ballen, Siddhartha Ganguly, Yachiyo Kuwatsuka, Wael Saber, Susana R. Marino, Sachiko Seo, Ruta Brazauskas, Baldeep Wirk, Shahrukh K. Hashmi, Christopher Bredeson, Yoshihiro Inamoto, Khalid Bo-Subait, Jean A. Yared, Gregory A. Hale, Navneet S. Majhail, Akshay Sharma, Harry C. Schouten, Saurabh Chhabra, Cesar O. Freytes, Jason Tay, Christopher E. Dandoy, Kehinde Adekola, Bronwen E. Shaw, Stefan O. Ciurea, David Gómez Almaguer, Hasan Hashem, Amir Steinberg, Hemant S. Murthy, Raquel M. Schears, Ayami Yoshimi, Linda J. Burns, David Szwajcer, David I. Marks, Tami John, Richard F. Olsson, Charles F. LeMaistre, William A. Wood, Jan Cerny, Susan K. Parsons, David Buchbinder, Usama Gergis, Nosha Farhadfar, Theresa Hahn, Mahmoud Aljurf, Hélène Schoemans, Sherif M. Badawy, Bipin N. Savani, Sara Beattie, Hillard M. Lazarus, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Hematologie (9), and Interne Geneeskunde
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Transplantation Conditioning ,AYA ,CHILDHOOD ,ADOLESCENT ,outcomes ,CANCER SURVIVORS ,immune system diseases ,hemic and lymphatic diseases ,Medicine ,Cumulative incidence ,Survivors ,Child ,intervention ,OUTCOMES ,Hematology ,Incidence (epidemiology) ,Stem cell transplantation ,Hematopoietic Stem Cell Transplantation ,transition ,health ,PREVALENCE ,surgical procedures, operative ,survivor ,HEALTH ,Survivor ,Life Sciences & Biomedicine ,INTERVENTION ,TRANSITION ,Adult ,medicine.medical_specialty ,Bone marrow transplantation ,Immunology ,prevalence ,Lost to follow-up ,stem cell transplantation ,Article ,Internal medicine ,Humans ,Transplantation, Homologous ,care ,Aged ,Transplantation ,Science & Technology ,business.industry ,Proportional hazards model ,CARE ,medicine.disease ,Confidence interval ,Lymphoma ,business ,Follow-Up Studies - Abstract
Follow-up is integral for hematopoietic cell transplantation (HCT) care to ensure surveillance and intervention for complications. We characterized the incidence of and predictors for being lost to follow-up. Two-year survivors of first allogeneic HCT (10,367 adults and 3865 children) or autologous HCT (7291 adults and 467 children) for malignant/nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected. The cumulative incidence of being lost to follow-up (defined as having missed 2 consecutive follow-up reporting periods) was calculated. Marginal Cox models (adjusted for center effect) were fit to evaluate predictors. The 10-year cumulative incidence of being lost to follow-up was 13% (95% confidence interval [CI], 12% to 14%) in adult allogeneic HCT survivors, 15% (95% CI, 14% to 16%) in adult autologous HCT survivors, 25% (95% CI, 24% to 27%) in pediatric allogeneic HCT survivors, and 24% (95% CI, 20% to 29%) in pediatric autologous HCT survivors. Factors associated with being lost to follow-up include younger age, nonmalignant disease, public/no insurance (reference: private), residence farther from the tranplantation center, and being unmarried in adult allogeneic HCT survivors; older age and testicular/germ cell tumor (reference: non-Hodgkin lymphoma) in adult autologous HCT survivors; older age, public/no insurance (reference: private), and nonmalignant disease in pediatric allogeneic HCT survivors; and older age in pediatric autologous HCT survivors. Follow-up focusing on minimizing attrition in high-risk groups is needed to ensure surveillance for late effects. ispartof: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION vol:26 issue:3 pages:553-561 ispartof: location:United States status: published
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- 2020
25. Technical and economic viability of manual harvesting coffee yield maps
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Brenon Diennevan Souza Barbosa, Diego José Carvalho Alonso, Fábio Moreira da Silva, Miguel Angel Diaz Herrera, Rafael de Oliveira Faria, Daniel Veiga Soares, and Gabriel Araújo e Silva Ferraz
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Thematic map ,Yield (wine) ,Linear regression ,Soil Science ,Sampling (statistics) ,Sample (statistics) ,Plant Science ,Precision agriculture ,Agricultural engineering ,Discount points ,Hectare ,Food Science ,Mathematics - Abstract
Precision coffee growing is a concept that implies the use of precision agriculture techniques in coffee plantations. For the coffee growing, the precision electronic resources coupled to the harvesters are very scarce. Thereby, the harvest of coffee plantations that compose the grid sampling for generation of thematic maps can be performed manually. The aim of the present study was to generate a linear regression model to estimate the time required to harvest, estimate the labor costs to harvest manually the georeferenced sample points for generation of coffee yield maps. The study was performed in a coffee area of 56 hectares using two sampling points per hectare, totaling 112 points, being evaluated four coffee plants for each point. The manual harvest of the points was performed by four rural workers with experience in the coffee harvest. Afterwards, the collected volume was measured by a graduated container and the times were obtained by the digital stopwatch. Based on the data obtained in the field, a linear correlation model was established between the harvest time of each sampling point and the yield of the point, whose R² value was 78.27, cost was R$ 8.92 per point. These results are relevant for estimating the amount of labor force required to generate manually harvest yield maps according to the producer’s coffee yield estimate, contributing to the closure of the precision coffee growing cycle. Key words: Precision agriculture; crop mapping; field efficiency; costs.
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- 2020
26. Comparison of High Doses of Total Body Irradiation in Myeloablative Conditioning before Hematopoietic Cell Transplantation
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Leona Holmberg, Lori Muffly, Alison W. Loren, Miguel-Angel Perales, Usama Gergis, Tao Wang, Christopher A. Barker, Betty K. Hamilton, Allistair Abraham, Peiman Hematti, Miguel Angel Diaz, Eva C. Guinan, Edward A. Stadtmauer, Sanghee Hong, Jeffery J. Auletta, Gerhard C. Hildebrandt, Marcelo C. Pasquini, Christopher Bredeson, Siddhartha Ganguly, Shin Mineishi, Shahrukh K. Hashmi, Caitrin Fretham, Robert Peter Gale, Hillard M. Lazarus, Jean-Yves Cahn, Kehinde Adekola, Jean A. Yared, Natasha Kekre, Cesar O. Freytes, Saurabh Chhabra, Taiga Nishihori, Rodrigo Martino, Amer Beitinjaneh, and Mitchell Sabloff
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Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Cyclophosphamide ,medicine.medical_treatment ,Malignancy ,Gastroenterology ,Disease-Free Survival ,Article ,03 medical and health sciences ,0302 clinical medicine ,Myeloablative conditioning ,Total body irradiation ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Transplantation ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Allogeneic hematopoietic cell transplantation ,Middle Aged ,Allografts ,medicine.disease ,Confidence interval ,Survival Rate ,Radiation therapy ,Hematologic Neoplasms ,030220 oncology & carcinogenesis ,Hematologic malignancies ,Female ,business ,Whole-Body Irradiation ,030215 immunology ,medicine.drug - Abstract
Malignancy relapse is the most common cause of treatment failure among recipients of hematopoietic cell transplantation (HCT). Conditioning dose intensity can reduce disease relapse but is offset by toxicities. Improvements in radiotherapy techniques and supportive care may translate to better outcomes with higher irradiation doses in the modern era. This study compares outcomes of recipients of increasing doses of high-dose total body irradiation (TBI) divided into intermediate high dose (IH; 13-13.75 Gy) and high dose (HD; 14 Gy) with standard dose (SD; 12 Gy) with cyclophosphamide. A total of 2721 patients ages 18 to 60 years with hematologic malignancies receiving HCT from 2001 to 2013 were included. Cumulative incidences of nonrelapse mortality (NRM) at 5 years were 28% (95% confidence interval [CI], 25% to 30%), 32% (95% CI, 29% to 36%), and 34% (95% CI, 28% to 39%) for SD, IH, and HD, respectively (P = .02). Patients receiving IH-TBI had a 25% higher risk of NRM compared with those receiving SD-TBI (12 Gy) (P = .007). Corresponding cumulative incidences of relapse were 36% (95% CI, 34% to 38%), 32% (95% CI, 29% to 36%), and 26% (95% Cl, 21% to 31%; P = .001). Hazard ratios for mortality compared with SD were 1.06 (95% CI,.94 to 1.19; P = .36) for IH and .89 (95% CI,.76 to 1.05; P = .17) for HD. The study demonstrates that despite improvements in supportive care, myeloablative conditioning using higher doses of TBI (with cyclophosphamide) leads to worse NRM and offers no survival benefit over SD, despite reducing disease relapse. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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- 2019
27. Choice of conditioning regimens for bone marrow transplantation in severe aplastic anemia
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Christopher C. Dvorak, James Gajewski, Amer Beitinjaneh, Jaap Jan Boelens, David Gómez-Almaguer, Miguel Angel Diaz, Usama Gergis, Hillard M. Lazarus, Mahmoud Aljurf, Joseph H. Antin, Michael A. Pulsipher, Paul J. Orchard, Jean A. Yared, Soyoung Kim, Marta González Vicent, Hisham Abdel-Azim, Kyle Hebert, Andrew R. Gennery, Bipin N. Savani, Ann E. Woolfrey, Biju George, Hasan Hashem, Blachy J. Dávila Saldaña, Kimberly A. Kasow, Natasha Kekre, Olle Ringdén, Daniel J. Weisdorf, Rammurti T. Kamble, Vikram Mathews, Sherif M. Badawy, Kirk R. Schultz, Robert Peter Gale, Siddhartha Ganguly, Mary Eapen, Shahinaz M. Gadalla, Jacek Winiarski, Ibrahim Ahmed, Nelli Bejanyan, and Pierre Teira
- Subjects
Homologous ,Adult ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Cyclophosphamide ,Anemia ,Clinical Decision-Making ,Graft vs Host Disease ,Regenerative Medicine ,Lower risk ,Severity of Illness Index ,Gastroenterology ,Young Adult ,Rare Diseases ,Stem Cell Research - Nonembryonic - Human ,HLA Antigens ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Bone Marrow Transplantation ,Transplantation ,business.industry ,Prevention ,Histocompatibility Testing ,Siblings ,Aplastic ,Anemia, Aplastic ,Disease Management ,Hematology ,Total body irradiation ,Stem Cell Research ,Prognosis ,medicine.disease ,Fludarabine ,Good Health and Well Being ,Treatment Outcome ,surgical procedures, operative ,business ,Busulfan ,medicine.drug - Abstract
Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n = 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P = .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P < .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged >30 years after HLA-matched sibling (HR, 2.74; P < .001) or unrelated donor (HR, 1.98; P = .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.
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- 2019
28. WITHDRAWN: Malformación venosa verrugosa y sobrecrecimiento: a propósito de 2 casos
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M Velayos, K Estefanía-Fernández, Juan Carlos López-Gutiérrez, Miguel Angel Diaz, P Triana, MC Sarmiento-Caldas, L Moratilla-Lapeña, V Martínez González, and L Rodriguez Laguna
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General Medicine - Abstract
The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.36959/472/363. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
- Published
- 2021
29. Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes
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Mohamed A. Kharfan-Dabaja, Leo F. Verdonck, Tania Jain, Gregory A. Hale, Navneet S. Majhail, Baldeep Wirk, Caitrin Fretham, Mahmoud Aljurf, Hemant S. Murthy, Kwang Woo Ahn, Ulrike Bacher, Wael Saber, Bart L. Scott, Jean Yves-Cahn, Daniel J. Weisdorf, Nosha Farhadfar, Richard F. Olsson, Michael R. Grunwald, Amer Beitinjaneh, Bipin N. Savani, Christopher Bredeson, Mark R. Litzow, Shatha Farhan, Jean A. Yared, Sachiko Seo, Jeff Szer, Gerhard C. Hildebrandt, Jan Cerny, David A. Rizzieri, Mitchell Sabloff, Ran Reshef, Vaibhav Agrawal, Robert Peter Gale, Ryotaro Nakamura, Saurabh Chhabra, Attaphol Pawarode, Taiga Nishihori, David I. Marks, Uday R. Popat, Siddhartha Ganguly, Miguel Angel Diaz, Betul Oran, Matt Kalaycio, Edward A. Copelan, Asad Bashey, Hillard M. Lazarus, Jane L. Liesveld, Shahrukh K. Hashmi, Marjolein van der Poel, Sunita Nathan, MUMC+: MA Hematologie (9), Interne Geneeskunde, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and MUMC+: MA Med Staf Artsass Interne Geneeskunde (9)
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Melphalan ,medicine.medical_specialty ,Survival ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,ACUTE MYELOID-LEUKEMIA ,RELAPSE ,Gastroenterology ,MALIGNANCIES ,hemic and lymphatic diseases ,Internal medicine ,VERSUS-HOST-DISEASE ,medicine ,MDS ,Immunology and Allergy ,ALLOGENEIC TRANSPLANTATION ,Transplantation ,business.industry ,CONDITIONING REGIMENS ,MUTATIONS ,Myelodysplastic syndromes ,STEM-CELL TRANSPLANTATION ,Cell Biology ,Hematology ,medicine.disease ,CYTOGENETICS ,Fludarabine ,Regimen ,Molecular Medicine ,Alemtuzumab ,610 Medizin und Gesundheit ,business ,Busulfan ,medicine.drug - Abstract
Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age >= 60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose
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- 2021
30. Planned granulocyte-colony stimulating factor adversely impacts survival after allogeneic hematopoietic cell transplantation performed with Thymoglobulin for myeloid malignancy
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Miguel Angel Diaz, David Szwajcer, Lynette C.Y. Chee, Claudio G. Brunstein, Mary Eapen, Nina Orfali, David A. Rizzieri, Timothy Prestidge, Ian K. McNiece, Olle Ringdén, Melhem Solh, Pashna N. Munshi, Michael R. Grunwald, Sachiko Seo, Hillard M. Lazarus, Muhammad Bilal Abid, Mei-Jie Zhang, Filippo Milano, Jean A. Yared, Peiman Hematti, Jaap Jan Boelens, Mariam Allbee-Johnson, Marcie L. Riches, Scott D. Solomon, Andrew S. Artz, Jingmei Hsu, and Koen van Besien
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Oncology ,medicine.medical_specialty ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Adolescent ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Filgrastim ,Article ,hemic and lymphatic diseases ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,medicine ,Immunology and Allergy ,Humans ,Transplantation, Homologous ,Antilymphocyte Serum ,Transplantation ,Thymoglobulin ,business.industry ,Hematopoietic Stem Cell Transplantation ,Cell Biology ,Hematology ,Middle Aged ,Donor Lymphocytes ,medicine.disease ,Anti-thymocyte globulin ,Granulocyte colony-stimulating factor ,Leukemia ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,Molecular Medicine ,business ,medicine.drug - Abstract
The in vivo depletion of recipient and donor T lymphocytes using antithymocyte globulin (ATG; Thymoglobulin) is widely adopted in allogeneic hematopoietic stem cell transplantation (HCT) to reduce the incidence of both graft failure and graft-versus-host disease (GVHD). However, excess toxicity to donor lymphocytes may hamper immune reconstitution, compromising antitumor effects and increasing infection. Granulocyte-colony stimulating factor (G-CSF) administered early after HCT may increase ATG-mediated lymphotoxicity. This study aimed to investigate the effect of an interaction between ATG and post-transplantation granulocyte colony-stimulating factor (G-CSF) on allogeneic HCT outcomes, using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. We studied patients age ≥18 years with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) who received Thymoglobulin-containing preparative regimens for HLA-matched sibling/unrelated or mismatched unrelated donor HCT between 2010 and 2018. The effect of planned G-CSF that was started between pretransplantation day 3 and post-transplantation day 12 was studied in comparison with transplantations that did not include G-CSF. Cox regression models were built to identify risk factors associated with outcomes at 1 year after transplantation. A total of 874 patients met the study eligibility criteria, of whom 459 (53%) received planned G-CSF. HCT with planned G-CSF was associated with a significantly increased risk for nonrelapse mortality (NRM) (hazard ratio [HR] 2.03; P.0001; 21% versus 12%) compared to HCT without G-CSF. The 6-month incidence of viral infection was higher with G-CSF (56% versus 47%; P = .007), with a particular increase in Epstein-Barr virus infections (19% versus 11%; P = .002). The observed higher NRM with planned G-CSF led to lower overall survival (HR, 1.52; P = .0005; 61% versus 72%). There was no difference in GVHD risk between the treatment groups. We performed 2 subgroup analyses showing that our findings held true in patients age ≥50 years and in centers where G-CSF was used in some, but not all, patients. In allogeneic peripheral blood HCT performed with Thymoglobulin for AML and MDS, G-CSF administered early post-transplantation resulted in a 2-fold increase in NRM and a 10% absolute decrement in survival. The use of planned G-CSF in the early post-transplantation period should be carefully considered on an individual patient basis, weighing any perceived benefits against these risks.
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- 2021
31. First Late Effect in Pediatric Survivors with Chronic Graft-Versus-Host Disease Following Hematopoietic Cell Transplantation for Hematologic Malignancy
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Peiman Hematti, Daniel R. Couriel, Sagar S. Patel, Minoo Battiwalla, Lazaros J. Lekakis, Sanghee Hong, Catherine J. Lee, Jeffery J. Auletta, Scott R. Solomon, Leo F. Verdonck, Mukta Arora, Joseph Pidala, Margaret L. MacMillan, Shahinaz M. Gadalla, Shahrukh K. Hashmi, Hasan Hashem, Karen Chen, Stephen R. Spellman, Yoshihiro Inamoto, Sherif M. Badawy, Zachariah DeFilipp, Vijaya Raj Bhatt, Nasheed Hossain, Anita J. Kumar, Rammurti T. Kamble, Tao Wang, Miguel Angel Diaz, Carrie L. Kitko, Robert Peter Gale, Nosha Farhadfar, David Buchbinder, Bipin N. Savani, Dipenkumar Modi, Akshay Sharma, and Jean-Yves Cahn
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Oncology ,Transplantation ,medicine.medical_specialty ,Hematopoietic cell ,business.industry ,Late effect ,Cell Biology ,Hematology ,medicine.disease ,Graft-versus-host disease ,Internal medicine ,Hematologic malignancy ,medicine ,Molecular Medicine ,Immunology and Allergy ,medicine.symptom ,business - Published
- 2021
32. Transplantation for Congenital Sideroblastic Anaemia Is Feasible and Offers Outcomes Comparable to Other Transfusion Dependent Anaemias. a Joint Retrospective Study of the Paediatric Diseases and Severe Aplastic Anaemia Working Parties (PDWP/SAAWP) of EBMT
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Régis Peffault de Latour, Carlo Dufour, Miguel Angel Diaz, Vassiliki Kitra-Roussou, John Moppett, Antonio M. Risitano, Abdelghani Tbakhi, John G. Gribben, Antonio Martinez, Tessa Kerre, Tobias Gedde-Dahl, Henrik Sengeloev, Muhlis Cem Ar, Josu de la Fuente, Cristina Díaz de Heredia, Paul Bosman, Mohamed Salaheldin Mohamed, Dominique Bron, Stig Lenhoff, José M. Moraleda, Hendrik Veelken, Giuseppe Visani, Selim Corbacioglu, Peter J. Shaw, Amal Al-Seraihy, Brenda Gibson, Dirk-Jan Eikema, Rupert Handgretinger, Estelle Verburgh, and Robert Wynn
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Pediatrics ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,education ,Immunology ,Retrospective cohort study ,Cell Biology ,Hematology ,Treosulfan ,medicine.disease ,Biochemistry ,Fludarabine ,Transplantation ,Regimen ,medicine ,Alemtuzumab ,Reticulocytopenia ,business ,health care economics and organizations ,medicine.drug - Abstract
Congenital sideroblastic anaemias (CSA) are a rare group of disorders characterized by the presence of pathologic iron deposits within the mitochondria of erythroid precursors (ring sideroblasts) in the bone marrow due to heterogenous germline mutations leading to defects in mitochondrial heme synthesis, iron-sulfur (Fe-S) cluster biogenesis, or protein synthesis. Patients present with anaemia and relative reticulocytopenia, and systemic iron overload secondary to chronic ineffective erythropoiesis, leading to end-organ damage. The disease is heterogenous underlying the genetic variability and the variable response to treatment. Although a number of CSA patients have received a bone marrow transplant, the outcomes and toxicities are not known. This status makes it very difficult to understand the role of BMT in the management of CSA. A search in the EBMT database identified 28 patients receiving a HSCT for CSA between 1998 to 2018 by 24 participating centres. The median year of transplantation was 2014 (IQR 2004-2016). The distribution was equal between males (n=14) and females (n=14). The median age at transplantation was 7 years of age (3-10 years). Fifteen patients had a sibling HSCT (88%), one a family matched donor HSCT (6%) and one an unrelated matched (6%), the type of transplant being unknown in others (n=11). The source of stem cells was bone marrow in 20 cases (74%), peripheral blood in 4 cases (15%), cord blood in 2 (7%) and combined bone marrow and cord in one (4%). Five cases had a Bu/Cy based conditioning regimen, 4 had Bu/fludarabine based regimen and three fludarabine/treosulfan based conditioning with the rest having a variety of approaches. Eighty-six percent of cases had serotherapy with ATG or alemtuzumab. The median follow-up was 31.6 months (95% CI, 12.2-74.1%). The overall survival at 12 and 24 months was 88% (76-100) and 82% (66-99), respectively (figure 1). The median neutrophil engraftment was 18 (15-21) days and platelet engraftment >20 x 109/L was 29 (20-51) days, with a graft failure incidence of 7% (0-17) at 12 months. Two patients suffered from VOD. There were four deaths, three of which were related to transplant complications. The event free survival (survival without graft failure, relapse and second transplant) at 12 and 24 months was 85% (72-99) (figure 2). Six patients developed acute GvHD grade II and one case grade III; giving a grade II/III incidence of 28% (10-46). There was one case of limited and one of chronic GvHD, giving an incidence of 11% (0-26%) at 12 months and 24 months. In conclusion, whilst HSCT for CSA is a rare occurrence, these data demonstrate that HSCT for this condition is feasible and the outcomes are in keeping with those obtained for transplantation for transfusion dependent anaemias during the same time-period. Disclosures Handgretinger: Amgen: Honoraria. Moraleda:Gilead: Consultancy, Other: Travel Expenses; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy, Other: Travel Expenses; Sandoz: Consultancy, Other: Travel Expenses; Takeda: Consultancy, Other: Travel Expenses. Risitano:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Jazz: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Samsung: Membership on an entity's Board of Directors or advisory committees; Amyndas: Consultancy; RA pharma: Research Funding; Biocryst: Membership on an entity's Board of Directors or advisory committees; Apellis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees; Pfizer: Speakers Bureau. Peffault De Latour:Amgen: Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.
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- 2020
33. Verrucous Venous Malformation and Overgrowth: About Two Cases
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P Triana, Miguel Angel Diaz, L Rodriguez Laguna, V Martínez González, M Velayos, Juan Carlos López-Gutiérrez, L Moratilla-Lapeña, MC Sarmiento-Caldas, and K Estefanía-Fernández
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medicine.anatomical_structure ,Dermis ,business.industry ,medicine ,Fascia ,Anatomy ,General Agricultural and Biological Sciences ,business ,medicine.disease ,Venous malformation ,Subcutaneous tissue ,Angiokeratoma - Abstract
Verrucous venous malformations (VVM), previously known as verrucous hemangiomas, are rare congenital vascular anomalies that initially appear as flat blue-red lesions that progressively evolve into very characteristic wart and hyperkeratotic forms. They mainly affect the lower extremities and, unlike angiokeratoma, they extend into the deep dermis, subcutaneous tissue and even reach the fascia.
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- 2021
34. Correction to: Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era
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Asad Bashey, Mohamed A. Kharfan-Dabaja, Omar Davila, Melhem Solh, Jeffrey Schriber, Keith Stockerl-Goldstein, Nosha Farhadfar, Cesar O. Freytes, Sachiko Seo, Cindy Lee, Jan Cerny, Sagar S. Patel, Miguel Angel Diaz, Robert F. Cornell, Raphael Fraser, Richard F. Olsson, Jesus G. Berdeja, Muzaffar H. Qazilbash, Leona Holmberg, Kenneth R. Meehan, Abraham S. Kanate, Saurabh Chhabra, Attaphol Pawarode, Amr Hanbali, Hillard M. Lazarus, Anita D'Souza, Taiga Nishihori, Wilson I. Gonsalves, David H. Vesole, Reinhold Munker, Gerhard C. Hildebrandt, Nina Shah, Jean A. Yared, Amer Assal, Parameswaran Hari, Sherif M. Badawy, Robert Peter Gale, Saulius Girnius, Binod Dhakal, Shahrukh K. Hashmi, Shaji Kumar, Lohith S. Bachegowda, Ruthlee Lu Bayer, Qaiser Bashir, Yvonne A. Efebera, Hemant S. Murthy, and Yago Nieto
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Plasma cell leukemia ,Transplantation ,Cancer Research ,Leukemia ,Oncology ,Hematopoietic cell ,business.industry ,medicine ,Cancer research ,Hematology ,medicine.disease ,business ,Article - Published
- 2021
35. Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation
- Author
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Lawrence S. Lamb, Hemalatha G. Rangarajan, Ran Reshef, Rodrigo Martino, Mahmoud Aljurf, Parinda A. Mehta, Sachiko Seo, Aleksandr Lazaryan, Hisham Abdel-Azim, Miguel Angel Diaz, Vijaya Raj Bhatt, Jean-Yves Cahn, Olle Ringdén, Robert Peter Gale, Jean A. Yared, Shatha Farhan, Usama Gergis, Daniel R. Couriel, Sagar S. Patel, Peiman Hematti, Betty K. Hamilton, Paul Castillo, Mukta Arora, Bipin N. Savani, Lolie C. Yu, Muna Qayed, Leo F. Verdonck, Abraham S. Kanate, Shahinaz M. Gadalla, David Buchbinder, Manish J. Gandhi, Rammurti T. Kamble, Saurabh Chhabra, Mitchell S. Cairo, Tao Wang, Takanori Teshima, Stephen R. Spellman, Kirk R. Schultz, Hadar A. Frangoul, Vaibhav Agrawal, Taiga Nishihori, Yngvar Fløisand, Amer Beitinjaneh, Michael T. Hemmer, Baldeep Wirk, Pooja Khandelwal, Gerhard C. Hildebrandt, Michael Byrne, Shahrukh K. Hashmi, Ravi Vij, Alvaro Urbano-Ispizua, James Gajewski, Richard F. Olsson, Ayman Saad, Joseph Pidala, Harry C. Schouten, Margaret L. MacMillan, Brian C. Shaffer, Basem M. William, Amin M. Alousi, Edmund K. Waller, David I. Marks, Melhem Solh, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Hematologie (9), and Interne Geneeskunde
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CD4-Positive T-Lymphocytes ,Male ,SELECTION ,GVHD dose ,Graft vs Host Disease ,CD8-Positive T-Lymphocytes ,Gastroenterology ,HLA Antigens ,Recurrence ,hemic and lymphatic diseases ,VERSUS-HOST-DISEASE ,Cumulative incidence ,CD34(+) ,Univariate analysis ,Acute leukemia ,Leukemia ,IMPROVED SURVIVAL ,Hematology ,Middle Aged ,Allografts ,Survival Rate ,medicine.anatomical_structure ,Acute Disease ,Female ,GRAFTS ,Stem cell ,Adult ,medicine.medical_specialty ,Adolescent ,T cell ,BONE-MARROW ,CD4-CD8 Ratio ,Human leukocyte antigen ,ACUTE MYELOID-LEUKEMIA ,CHRONIC GVHD ,Disease-Free Survival ,Internal medicine ,medicine ,Humans ,Allogeneic ,Peripheral Blood Stem Cell Transplantation ,Transplantation ,business.industry ,CD3(+) CELLS ,Myelodysplastic Syndromes ,RISK-FACTORS ,business ,Ex vivo ,CD8 - Abstract
Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3(+) T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3(+) T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3(+) T cell dose cutoff of 14 x 10(7) cells/kg identified MSD/low CD3(+) (n = 223) and MSD/high CD3(+) (n = 1214), and a dose of 15 x 107 cells/kg identified MUD/low (n = 197) and MUD/high CD3(+) (n = 1102). On univariate analysis, the MSD/high CD3(+) group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3(+) group (33% versus 25%; P=.009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3(+) group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3(+) group (49% versus 41%; P=.04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3(+) T cell dose and the risk of either aGVHD grade II-IV (P=.10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4(+) T cells, CD8(+) T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3(+) T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4(+) and CD8(+) T cell doses were not possible given our small sample size. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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- 2019
36. GRFS and CRFS in alternative donor hematopoietic cell transplantation for pediatric patients with acute leukemia
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Ayman Saad, Baldeep Wirk, Usama Gergis, Melhem Solh, Muna Qayed, Robert Peter Gale, Leo F. Verdonck, Rohtesh S. Mehta, Niketa Shah, Mahmoud Aljurf, Gerhard C. Hildebrandt, Sachiko Seo, Tim Prestidge, Thomas R. Spitzer, Vijaya Raj Bhatt, David I. Marks, Attaphol Pawarode, Taiga Nishihori, Mukta Arora, Hisham Abdel-Azim, Miguel Angel Diaz, Joseph Pidala, Ami J. Shah, Margaret L. MacMillan, Michael T. Hemmer, James Gajewski, Medhat Askar, Hemalatha G. Rangarajan, Ibrahim Ahmed, Yoshihiro Inamoto, Jean A. Yared, Stephen R. Spellman, Carrie L. Kitko, Richard F. Olsson, Christopher Bredeson, Amin M. Alousi, Tao Wang, Takanori Teshima, Kirk R. Schultz, Kirsten M. Williams, Jeff Szer, Bipin N. Savani, Daniel R. Couriel, Pooja Khandelwal, Shahinaz M. Gadalla, Saurabh Chhabra, Parinda A. Mehta, Olle Ringdén, Shernan G. Holtan, Navneet S. Majhail, Peiman Hematti, Jeffery J. Auletta, Daniel J. Weisdorf, and John E. Wagner
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Male ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,Graft vs Host Disease ,Bone Marrow Cells ,Hematopoietic stem cell transplantation ,Thyroglobulin ,Gastroenterology ,Disease-Free Survival ,Recurrence ,Internal medicine ,Acute lymphocytic leukemia ,Humans ,Medicine ,Child ,Alemtuzumab ,Survival rate ,Proportional Hazards Models ,Transplantation ,Acute leukemia ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Fetal Blood ,medicine.disease ,Survival Rate ,Leukemia, Myeloid, Acute ,Leukemia ,Graft-versus-host disease ,Child, Preschool ,Female ,business ,Whole-Body Irradiation ,medicine.drug - Abstract
We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy–requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen–mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation–based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.
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- 2019
37. Revised International Staging System Is Predictive and Prognostic for Early Relapse (<24 months) after Autologous Transplantation for Newly Diagnosed Multiple Myeloma
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Ayman Saad, Tamila L. Kindwall-Keller, Raphael Fraser, Sathish Kumar Gopalakrishnan, Rammurti T. Kamble, Anita D'Souza, Cesar O. Freytes, Melhem Solh, Robert A. Kyle, Hillard M. Lazarus, Jesus G. Berdeja, Siddhartha Ganguly, Robert Peter Gale, Taiga Nishihori, Parameswaran Hari, Kenneth R. Meehan, Tomer M Mark, Saad Z. Usmani, Cindy Lee, Miguel Angel Diaz, Usama Gergis, Binod Dhakal, Abraham S. Kanate, Shaji Kumar, Amer Assal, Omar Davila, Emma C. Scott, Frederick L. Locke, Yago Nieto, Cristina Gasparetto, Gerhard C. Hildebrandt, Bipin N. Savani, Nina Shah, and Sachiko Seo
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Adult ,Male ,Oncology ,medicine.medical_specialty ,Transplantation Conditioning ,health care facilities, manpower, and services ,Early Relapse ,Newly diagnosed ,Transplant ,Transplantation, Autologous ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Recurrence ,health services administration ,Internal medicine ,Lactate dehydrogenase ,medicine ,Humans ,Autologous transplantation ,Staging system ,Multiple myeloma ,Aged ,Neoplasm Staging ,Transplantation ,business.industry ,Myeloma stage ,Hematopoietic Stem Cell Transplantation ,food and beverages ,Hematology ,Middle Aged ,Prognosis ,medicine.disease ,Postrelapse survival ,chemistry ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,business ,human activities ,030215 immunology - Abstract
The revised International Staging System (R-ISS) combines ISS with genetic markers and lactate dehydrogenase and can prognosticate newly diagnosed multiple myeloma (MM). Early relapse (
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- 2019
38. Virus detection in the cerebrospinal fluid of hematopoietic stem cell transplant recipients is associated with poor patient outcomes: a CIBMTR contemporary longitudinal study
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Marcie L. Riches, Jaime S. Green, Maheen Z. Abidi, Dwight E Yin, Taiga Nishihori, Min Chen, Celalettin Ustun, Caroline A. Lindemans, John R. Wingard, Joshua A. Hill, Baldeep Wirk, Robert Peter Gale, Usama Gergis, Richard F. Olsson, Parameswaran Hari, Hillard M. Lazarus, Gerhard C. Hildebrandt, Jeffrey Auletta, Krishna V. Komanduri, Sachiko Seo, David Marks, Minoo Battiwala, Miguel Angel Diaz, Parastoo B. Dahi, Jean A. Yared, Soyoung Kim, and Siddhartha Ganguly
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Male ,Transplantation Conditioning ,viruses ,Regenerative Medicine ,medicine.disease_cause ,Gastroenterology ,0302 clinical medicine ,Stem Cell Research - Nonembryonic - Human ,Viral ,Longitudinal Studies ,Child ,Cancer ,education.field_of_study ,Hematology ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Fludarabine ,Infectious Diseases ,Virus Diseases ,Child, Preschool ,030220 oncology & carcinogenesis ,Cord blood ,HIV/AIDS ,Female ,Infection ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Population ,Viremia ,Article ,Virus ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Preschool ,education ,Aged ,Transplantation ,business.industry ,Varicella zoster virus ,DNA ,Stem Cell Research ,medicine.disease ,Good Health and Well Being ,DNA, Viral ,business ,030215 immunology - Abstract
Limited data exist on characteristics of central nervous system viruses (CNS-V) in allogeneic hematopoietic stem cell transplant (HCT) recipients. Between 2007 and 2015, the Center for International Blood and Marrow Transplant Research (CIBMTR) received information on 27,532 patients undergoing HCT. Of these, centers reported 165 HCT recipients with CNS-V detected in cerebrospinal fluid within six months after HCT. CNS viruses predominantly included human herpes virus 6 (HHV-6) (73%), followed by Epstein-Barr Virus (10%), cytomegalovirus (3%), varicella zoster virus (3%), herpes simplex virus (3%) and Adenovirus (3%). Median time of viral detection in CNS was 31 days after HCT; and viral detection was earlier in patients with CNS HHV-6. Concurrent viremia occurred in 52% of patients. Cord blood transplant recipients (CBT) accounted for the majority (53%) of patients with CNS-V. Myeloablative conditioning (65%), use of fludarabine (63%), or use of anti-thymocyte globulin (61%) were also predominant. Overall survival from the time of detection of CNS-V was 50% at 6 months and 30% at 5 years. Infections were the leading cause of death (32%). In summary, CBT recipients predominated in the population with CNS-V. Outcomes after CNS-V were poor with significant mortality seen in the first 6 months.
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- 2019
39. Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia
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Hemant S. Murthy, Kwang Woo Ahn, Noel Estrada-Merly, Hassan B. Alkhateeb, Susan Bal, Mohamed A. Kharfan-Dabaja, Bhagirathbhai Dholaria, Francine Foss, Lohith Gowda, Deepa Jagadeesh, Craig Sauter, Muhammad Bilal Abid, Mahmoud Aljurf, Farrukh T. Awan, Ulrike Bacher, Sherif M. Badawy, Minoo Battiwalla, Chris Bredeson, Jan Cerny, Saurabh Chhabra, Abhinav Deol, Miguel Angel Diaz, Nosha Farhadfar, César Freytes, James Gajewski, Manish J. Gandhi, Siddhartha Ganguly, Michael R. Grunwald, Joerg Halter, Shahrukh Hashmi, Gerhard C. Hildebrandt, Yoshihiro Inamoto, Antonio Martin Jimenez-Jimenez, Matt Kalaycio, Rammurti Kamble, Maxwell M. Krem, Hillard M. Lazarus, Aleksandr Lazaryan, Joseph Maakaron, Pashna N. Munshi, Reinhold Munker, Aziz Nazha, Taiga Nishihori, Olalekan O. Oluwole, Guillermo Ortí, Dorothy C. Pan, Sagar S. Patel, Attaphol Pawarode, David Rizzieri, Nakhle S. Saba, Bipin Savani, Sachiko Seo, Celalettin Ustun, Marjolein van der Poel, Leo F. Verdonck, John L. Wagner, Baldeep Wirk, Betul Oran, Ryotaro Nakamura, Bart Scott, Wael Saber, Interne Geneeskunde, MUMC+: MA Hematologie (9), and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
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Transplantation ,Transplantation Conditioning ,ALEMTUZUMAB ,Hematopoietic Stem Cell Transplantation ,MULTICENTER ,Graft vs Host Disease ,610 Medicine & health ,Cell Biology ,Hematology ,Middle Aged ,GLOBULIN ,T-PLL ,Article ,Allogeneic stem cell transplant ,Leukemia, Prolymphocytic, T-Cell ,UNRELATED DONORS ,SURVIVAL ,Molecular Medicine ,Immunology and Allergy ,Humans ,Transplantation, Homologous ,TRIAL ,Prolymphocytic leukemia - Abstract
T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) 90 or chemosensitive disease.
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- 2022
40. Defibrotide in hematopoietic stem cell transplantation: A multicenter survey study of the Spanish Hematopoietic Stem Cell Transplantation Group (GETH)
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Ildefonso Espigado, Miguel Angel Diaz, Isabel Badell, Ignacio Gómez Centurión, Jesús González de Pablo, Ana Isabel Gallardo, Blanca Molina, Cristina Beléndez, Marta González Vicent, Pedro Gonzalez, Lucía López Corral, Manuel Guerreiro, José María Fernández, Esperanza Lavilla, Ariadna Pérez, Mónica Duarte, Antonio Martinez, Alexandra Regueiro, María J. Jiménez, Lissette Costilla, Cristina Díaz de Heredia, Albert Esquirol, Leyre Bento, Alexandra Pedraza, Carlos Vallejo, Pilar Palomo, O. J. Lopez, Julia Marsal, Ana Jiménez Ubieto, Estefanía García, and A. Benito
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Male ,medicine.medical_treatment ,genetic processes ,Hematopoietic stem cell transplantation ,Defibrotide ,defibrotide ,hematopoietic transplantation ,0302 clinical medicine ,Child ,media_common ,Cause of death ,Hematopoietic Stem Cell Transplantation ,Hematology ,General Medicine ,Middle Aged ,Allografts ,Survival Rate ,Safety profile ,surgical procedures, operative ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Thrombotic microangiopathy ,Adolescent ,Disease-Free Survival ,03 medical and health sciences ,Polydeoxyribonucleotides ,Internal medicine ,medicine ,Humans ,media_common.cataloged_instance ,European union ,Aged ,Retrospective Studies ,Thrombotic Microangiopathies ,business.industry ,Infant ,Retrospective cohort study ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,sinusoidal obstruction syndrome ,enzymes and coenzymes (carbohydrates) ,Spain ,Multicenter survey ,bacteria ,SOS, defibrotide, hematopoietic transplantation ,business ,030215 immunology - Abstract
BACKGROUND: Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT. METHODS: This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON). RESULTS: Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%). CONCLUSIONS: Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.
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- 2021
41. Allogeneic Transplantation to Treat Therapy Related MDS and AML in Adults
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Metheny, Leland, Callander, Natalie S, Hall, Aric C, Zhang, Mei-Jei, Bo-Subait, Khalid, Wang, Hai-Lin, Agrawal, Vaibhav, Al-Homsi, A Samer, Assal, Amer, Bacher, Ulrike, Beitinjaneh, Amer, Bejanyan, Nelli, Bhatt, Vijaya Raj, Bredeson, Chris, Byrne, Michael, Cairo, Mitchell, Cerny, Jan, DeFilipp, Zachariah, Perez, Miguel Angel Diaz, Freytes, César O, Ganguly, Siddhartha, Grunwald, Michael R, Hashmi, Shahrukh, Hildebrandt, Gerhard C, Inamoto, Yoshihiro, Kanakry, Christopher G, Kharfan-Dabaja, Mohamed A, Lazarus, Hillard M, Lee, Jong Wook, Nathan, Sunita, Nishihori, Taiga, Olsson, Richard F, Ringdén, Olov, Rizzieri, David, Savani, Bipin N, Savoie, Mary Lynn, Seo, Sachiko, van der Poel, Marjolein, Verdonck, Leo F, Wagner, John L, Yared, Jean A, Hourigan, Christopher S, Kebriaei, Partow, Litzow, Mark, Sandmaier, Brenda M, Saber, Wael, Weisdorf, Daniel, and de Lima, Marcos
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hemic and lymphatic diseases ,610 Medicine & health - Abstract
Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML) have a poor prognosis. An earlier CIBMTR analysis of allogeneic hematopoietic cell therapy (allo-HCT) (n=868, 1990-2004) showed 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%. Modern supportive care, graft versus host disease (GVHD) prophylaxis and reduced intensity conditioning (RIC) regimens have improved outcomes. Therefore, the Center for International Blood and Marrow Transplant Research (CIBMTR) analyzed 1531 allo-HCT for adults with t-MDS (n = 759) or t-AML (n = 772) performed from 2000 to 2014. Median age was 59 years (18-74) for t-MDS and 52 years (18-77) for t-AML. 24% of patient with t-MDS and 11% of patients with t-AML and had a prior autologous transplant. A myeloablative regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Non-relapse mortality (NRM) at five years was 34% (95% confidence interval (CI) 30-37) and 34% (30-37) for t-MDS and t-AML, respectively. Relapse rates at five years were 46% (43-50) and 43% (40-47), respectively. 5-year OS and DFS was 27% (23-31) and 19% (16-23) for patients with t-MDS and 25% (22-28) and 23% (20-26) for patients with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low risk t-MDS and those receiving MAC HCT during first complete remission (CR1) t-AML, but worse for those with prior autologous HCT, higher risk cytogenetics or IPSS-R score and partially matched unrelated donors (URD). Relapse remains the major cause of treatment failure with little improvement over the past two decades. These data indicate caution in recommending allo-HCT in these conditions and more effective anti-neoplastic approaches before and after allo-HCT. BACKGROUND Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML) have a poor prognosis. An earlier CIBMTR analysis of allogeneic hematopoietic cell therapy (allo-HCT) (n=868, 1990-2004) showed 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%. Modern supportive care, graft versus host disease (GVHD) prophylaxis and reduced intensity conditioning (RIC) regimens have improved outcomes. OBJECTIVES The primary objectives are OS and DFS. The secondary objectives are non-relapse mortality (NRM), relapse, GVHD rates and identifying prognostic factors for outcomes after allo-HCT. STUDY DESIGN The Center for International Blood and Marrow Transplant Research (CIBMTR) analyzed 1531 allo-HCT for adults with t-MDS (n = 759) or t-AML (n = 772) performed from 2000 to 2014. Cumulative incidence function was used to estimate relapse, NRM, acute and chronic GVHD. Kaplan-Meier estimate was used to calculate probabilities of OS and DFS. Cox proportional hazards regression model was used to estimate hazard ratio (HR) of patient / disease / transplant related factors for outcomes of interest. RESULTS The median age was 59 years (18-74) for t-MDS and 52 years (18-77) for t-AML. 24% of patient with t-MDS and 11% of patients with t-AML and had a prior autologous transplant. A myeloablative regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Non-relapse mortality (NRM) at five years was 34% (95% confidence interval (CI) 30-37) and 34% (30-37) for t-MDS and t-AML, respectively. Relapse rates at five years were 46% (43-50) and 43% (40-47), respectively. 5-year OS and DFS was 27% (23-31) and 19% (16-23) for patients with t-MDS and 25% (22-28) and 23% (20-26) for patients with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low risk t-MDS and those receiving MAC HCT during first complete remission (CR1) t-AML, but worse for those with prior autologous HCT, higher risk cytogenetics or IPSS-R score and partially matched unrelated donors (URD). CONCLUSIONS Relapse remains the major cause of treatment failure with little improvement over the past two decades. These data indicate caution in recommending allo-HCT in these conditions. Through better patient optimization, more effective conditioning and studies of post-HCT interventions, outcomes for patients with t-MDS and t-AML may improve.
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- 2021
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42. Natural killer cell alloreactivity in HLA-haploidentical hematopoietic transplantation: a study on behalf of the CTIWP of the EBMT
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Linda Koster, Mara Merluzzi, Miguel Angel Diaz, Loredana Ruggeri, Arnon Nagler, Andrea Velardi, Steffie van der Werf, Franco Locatelli, Pavel Jindra, José Luis Díez-Martín, Diderik-Jan Eikema, Chiara Bonini, Anja van Biezen, Antoine Toubert, Luca Vago, Christian Chabannon, Liesbeth C. de Wreede, Fabio Ciceri, José A. Pérez-Simón, Giuseppe Milone, Ruggeri, L., Vago, L., Eikema, D. -J., de Wreede, L. C., Ciceri, F., Diaz, M. A., Locatelli, F., Jindra, P., Milone, G., Diez-Martin, J. L., Perez-Simon, J. A., Merluzzi, M., Koster, L., van der Werf, S., van Biezen, A., Toubert, A., Nagler, A., Chabannon, C., Bonini, C., and Velardi, A.
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Myeloid ,NK ,Graft vs Host Disease ,Human leukocyte antigen ,Natural killer cell ,Cell therapy ,Mice ,Medicine ,Animals ,Humans ,Prospective Studies ,Prospective cohort study ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Hematology ,Killer Cells, Natural ,Haematopoiesis ,Leukemia, Myeloid, Acute ,surgical procedures, operative ,medicine.anatomical_structure ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Immunology ,Transplantation, Haploidentical ,business - Abstract
Human leukocyte antigen (HLA) class-I mismatches that trigger donor-versus-recipient natural killer (NK)-cell alloreactivity reduce the incidence of leukemia relapse and improve survival of acute myeloid leukemia patients after T-cell-depleted HLA-haplotype mismatched (“haploidentical”) hematopoietic transplantation. In murine graft-versus-host disease (GvHD) models, alloreactive NK-cells also prevent GvHD. Here we report the results of a non-interventional, prospective study performed on behalf of the Cellular Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation. The study was aimed at re-assessing the role of NK-cell alloreactivity in a cohort of haploidentical transplants performed in Europe between 2012 and 2015 and composed of unmanipulated, as well as T-cell-depleted transplants. One hundred thirty-eight patients with acute myeloid or lymphoid leukemias were analyzed. Eighty-six patients received ex-vivo T-cell-depleted transplants, 52 patients received unmanipulated transplants. Fifty patients were transplanted from NK alloreactive donors, 88 from non-NK alloreactive donors. NK cell alloreactivity did not impact on GvHD/relapse-free survival (GRFS) in unmanipulated transplants (HR: 1.66 (0.9–3.1), p = 0.1). In contrast, it did impact beneficially on GRFS in T-cell-depleted transplants (HR: 0.6, (0.3–1.2), p = 0.14, interaction p < 0.001). This effect was the consequence of reduced incidences of acute and chronic GvHD and non-relapse mortality.
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- 2021
43. No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease
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Stefan Burdach, I. Kazantsev, Andreas Ranft, Katja Gall, Susanne Jabar, A. Prete, Angela Wawer, Sebastian J. Schober, Michael Merker, Uta Dirksen, Hendrik Gassmann, I. von Lüttichau, Peter Bader, Peter Lang, Uwe Thiel, E. Koscielniak, T Klingebiel, B. Gruhn, B. Afanasyev, Rupert Handgretinger, Miguel Angel Diaz, Heribert Jürgens, and Marek Ussowicz
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,Medizin ,Graft vs Host Disease ,Cancer immunotherapy ,Sarcoma, Ewing ,Human leukocyte antigen ,Group A ,Gastroenterology ,Article ,Group B ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Acute graft versus host disease ,Advanced disease ,Humans ,Medicine ,Child ,Retrospective Studies ,Transplantation ,business.industry ,Bone metastases ,Hematopoietic Stem Cell Transplantation ,Correction ,Hematology ,Middle Aged ,medicine.disease ,ddc ,surgical procedures, operative ,030104 developmental biology ,Child, Preschool ,030220 oncology & carcinogenesis ,Sarcoma ,Neoplasm Recurrence, Local ,Stem cell ,business - Abstract
Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated with allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts (group B, n = 27). Median age at diagnosis was 13 years, and 15 years (range 3–49 years) at allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number of relapses at allo-SCT, or risk stratum. 9/39 (23%) group A versus 2/27 (7%) group B patients developed severe acute graft versus host disease (GvHD). Of patients alive at day 100, 7/34 (21%) group A versus 9/19 (47%) group B patients had developed chronic GvHD. In group A, 33/39 (85%) versus 20/27 (74%) group B patients died of disease and 1/39 (3%) versus 1/27 (4%) patients died of complications, respectively. Altogether 12/66 (18%) patients survived in CR. Median EFS 24 months after allo-SCT was 20% in both groups, median OS was 27% (group A) versus 17% (group B), respectively. There was no difference in EFS and OS in AES patients transplanted with HLA-mismatched versus HLA-matched graft in univariate and multivariate analyses. In this analysis, CR at allo-SCT is a condition for survival (p
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- 2020
44. Myeloablative Conditioning for Allogeneic Transplantation Results in Superior Disease-Free Survival for Acute Myelogenous Leukemia and Myelodysplastic Syndromes with Low/Intermediate but not High Disease Risk Index: A Center for International Blood and Marrow Transplant Research Study
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Neil Palmisiano, Reinhold Munker, Siddhartha Ganguly, Wael Saber, Hillard M. Lazarus, Miguel Angel Diaz, Attaphol Pawarode, Taiga Nishihori, Partow Kebriaei, Jan Cerny, Jean-Yves Cahn, Nasheed Hossain, Sunita Nathan, Baldeep Wirk, Sachiko Seo, Melhem Solh, Brenda M. Sandmaier, Christopher Bredeson, Nelli Bejanyan, Gregory A. Hale, Jakob Passweg, Edward A. Copelan, Harry C. Schouten, Cesar O. Freytes, Hai-Lin Wang, David A. Rizzieri, Biju George, Daniel J. Weisdorf, Natasha Kekre, Michael R. Grunwald, Stefan O. Ciurea, Marcos de Lima, Sergio Giralt, Vera Ulrike Bacher, Marjolein van der Poel, Richard F. Olsson, Michael Byrne, Rodrigo Martino, Mark R. Litzow, Khalid Bo-Subait, Jean A. Yared, Mei-Jie Zhang, Christopher S. Hourigan, Christopher G. Kanakry, Bipin N. Savani, Mitchell S. Cairo, Gerhard C. Hildebrandt, Erica D. Warlick, Robert Peter Gale, Mohamed A. Kharfan-Dabaja, Steven D. Gore, Claudio G. Brunstein, Leo F. Verdonck, Ajoy Dias, Mahmoud Aljurf, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Hematologie (9), and Interne Geneeskunde
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Oncology ,Transplantation Conditioning ,IMPACT ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,0302 clinical medicine ,AML ,hemic and lymphatic diseases ,MDS ,Immunology and Allergy ,Medicine ,610 Medicine & health ,Myeloablative ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Leukemia ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,WORKING PARTY ,Molecular Medicine ,REDUCED-INTENSITY ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,ACUTE MYELOID-LEUKEMIA ,REGIMENS ,Disease-Free Survival ,Article ,03 medical and health sciences ,Myelogenous ,Internal medicine ,Humans ,Transplantation, Homologous ,TERM-FOLLOW-UP ,Aged ,Retrospective Studies ,Transplantation ,MUTATIONS ,business.industry ,Myelodysplastic syndromes ,RIC ,STEM-CELL TRANSPLANTATION ,Cell Biology ,medicine.disease ,UNRELATED DONOR TRANSPLANTATION ,Myelodysplastic Syndromes ,DRI ,business ,030215 immunology - Abstract
Compared with reduced-intensity conditioning (RIC), myeloablative conditioning (MAC) is generally associated with lower relapse risk after allogeneic hematopoietic cell transplantation (HCT) for acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, disease-specific risk factors in AML/MDS can further inform when MAC and RIC may yield differential outcomes. We analyzed HCT outcomes stratified by the Disease Risk Index (DRI) in 4387 adults (age 40 to 65 years) to identify the impact of conditioning intensity. In the low/ intermediate-risk DRI cohort, RIC was associated with lower nonrelapse mortality (NRM) (hazard ratio [HR],.74; 95% confidence interval [CI],.62 to.88; P
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- 2020
45. Optimal donor for African Americans with hematologic malignancy: HLA-haploidentical relative or umbilical cord blood transplant
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Melhem Solh, Rizwan Romee, Edmund K. Waller, Saurabh Chhabra, Minoo Battiwalla, Scott R. Solomon, Nancy M. Hardy, Basem M. William, Olle Ringdén, Claudio G. Brunstein, Joseph P. McGuirk, Mary Eapen, Marjolein van der Poel, Peiman Hematti, Ephraim J. Fuchs, Mei-Jie Zhang, Miguel Angel Diaz Perez, Andrew St. Martin, Karen K. Ballen, Siddhartha Ganguly, David A. Rizzieri, Lee Ann Baxter-Lowe, David Szwajcer, Asad Bashey, Edward Peres, Interne Geneeskunde, MUMC+: MA Hematologie (9), and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
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Transplantation Conditioning ,IMPACT ,Stem Cell Research - Umbilical Cord Blood/ Placenta - Human ,GVHD ,Graft vs Host Disease ,Disease ,Regenerative Medicine ,Gastroenterology ,Umbilical cord ,Alternative donor ,0302 clinical medicine ,Stem Cell Research - Nonembryonic - Human ,CYCLOPHOSPHAMIDE ,African American ,race ,Cancer ,Histocompatibility Testing ,leukemia ,Hematopoietic Stem Cell Transplantation ,Transplant-Related Mortality ,Hematology ,Fetal Blood ,Tissue Donors ,Leukemia ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,SURVIVAL ,Cord Blood Stem Cell Transplantation ,ACCESS ,Stem Cell Research - Umbilical Cord Blood/ Placenta ,medicine.medical_specialty ,Clinical Sciences ,Immunology ,transplant-related mortality ,Human leukocyte antigen ,Caucasian ,Article ,HEMATOPOIETIC-CELL TRANSPLANTATION ,03 medical and health sciences ,Myelogenous ,Rare Diseases ,Clinical Research ,Internal medicine ,medicine ,Humans ,ACUTE-LEUKEMIA ,Transplantation ,Umbilical Cord Blood Transplantation ,business.industry ,GRAFT ,NEED ,ADULTS ,medicine.disease ,Stem Cell Research ,Black or African American ,Good Health and Well Being ,business ,030215 immunology - Abstract
Although hematopoietic cell transplantation from an HLA-matched unrelated donor is potentially curative for hematologic malignancies, survival is lower for African Americans compared with Caucasians. Because only approximately 20% of African Americans will have an HLA-matched unrelated donor, many of these patients undergo HLA-haploidentical relative or umbilical cord blood transplantation. In this study, we analyzed outcomes after HLA-haploidentical related donor (n = 249) and umbilical cord blood (n = 118) transplantations in African American patients with hematologic malignancy between 2008 and 2016. The predominant disease was acute myelogenous leukemia for recipients of both types of donor grafts. The incidences of grade II-IV and III-IV acute graft-versus-host disease were higher after umbilical cord blood transplantation compared with HLA-haploidentical relative transplantation (56% and 29%, respectively, versus 33% and 11%, respectively; P
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- 2020
46. Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases
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Baldeep Wirk, Parinda A. Mehta, Hemant S. Murthy, Bronwen E. Shaw, Michael Byrne, Amer Beitinjaneh, Peiman Hematti, Gerhard C. Hildebrandt, Stephanie Bo-Subait, Naynesh Kamani, Mary E.D. Flowers, Andrew R. Rezvani, Rachel Phelan, Kasiani C. Myers, Samantha J Mayo, Hillard M. Lazarus, Peter J. Shaw, Steven Z. Pavletic, Yoshihiro Inamoto, Cesar O. Freytes, David Buchbinder, Biju George, Larisa Broglie, Heather R. Tecca, Edward A. Copelan, Rammurti T. Kamble, Seth J. Rotz, Lynda M. Vrooman, Christine Duncan, Nosha Farhadfar, Minoo Battiwala, Robert J. Hayashi, Sherif M. Badawy, William J. Hogan, Siddhartha Ganguly, Ruta Brazauskas, Robert Peter Gale, Kirsten M. Williams, Kristin Page, Bipin N. Savani, Miguel Angel Diaz, Tim Prestidge, Blanche P. Alter, Raquel M. Schears, Allistair Abraham, Maxim Norkin, Andrew Daly, Neel S. Bhatt, Vaibhav Agrawal, Saurabh Chhabra, Jeffery J. Auletta, Taiga Nishihori, Celalettin Ustun, Prakash Satwani, Richard F. Olsson, Justine M. Kahn, and Amy K. Keating
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medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Population ,Hematopoietic stem cell transplantation ,Interquartile range ,Internal medicine ,Neoplasms ,medicine ,Humans ,Transplantation, Homologous ,Aplastic anemia ,education ,Child ,education.field_of_study ,Transplantation ,Leukemia ,business.industry ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Anemia, Aplastic ,Hematology ,medicine.disease ,Hemoglobinopathy ,business - Abstract
We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range
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- 2020
47. Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT
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Ayman Saad, Hemalatha G. Rangarajan, Olle Ringdén, Hélène Schoemans, Peiman Hematti, Vaibhav Agrawal, Baldeep Wirk, Navneet S. Majhail, Attaphol Pawarode, Taiga Nishihori, Joseph Pidala, James Gajewski, Zachariah DeFilipp, Andrew Daly, Michael T. Hemmer, Shernan G. Holtan, Rodrigo Martino, William J. Hogan, Daniel R. Couriel, Mukta Arora, Tim Prestidge, Melhem Solh, Thomas R. Spitzer, Gerhard C. Hildebrandt, Richard F. Olsson, Lynette Chee, Vijaya Raj Bhatt, Ibrahim Ahmed, Tao Wang, Takanori Teshima, Kirk R. Schultz, Joseph H. Antin, A. Samer Al-Homsi, Jean-Yves Cahn, Miguel Angel Diaz, Rohtesh S. Mehta, Usama Gergis, Leo F. Verdonck, David I. Marks, Jeffery J. Auletta, Medhat Askar, Hisham Abdel-Azim, Yoshihiro Inamoto, Amin M. Alousi, Mahmoud Aljurf, Daniel J. Weisdorf, Stephen R. Spellman, Sachiko Seo, Bipin N. Savani, Robert Peter Gale, Jean A. Yared, Saurabh Chhabra, and Jan Storek
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Graft vs Host Disease ,Cord Blood Stem Cell Transplantation ,Umbilical cord ,Young Adult ,Recurrence ,Internal medicine ,medicine ,Humans ,Young adult ,CRFS ,Alternative donor ,Aged ,Retrospective Studies ,business.industry ,Extramural ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,ORIGINAL REPORTS ,Middle Aged ,Chronic disease ,medicine.anatomical_structure ,Hematologic Neoplasms ,Chronic Disease ,Female ,business - Abstract
PURPOSE There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]–bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. METHODS We report composite end points of graft-versus-host disease (GVHD)–free relapse-free survival (GRFS) and chronic GVHD (cGVHD)–free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. RESULTS In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. CONCLUSION Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
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- 2020
48. Outcome of patients with Fanconi anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: A retrospective analysis on behalf of EBMT group
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Charlotte Jubert, Wolfgang Holter, Mahmoud Aljurf, Bénédicte Bruno, Claudia Rossig, Miguel Angel Diaz, Maura Faraci, Duygu Uckan-Cetinkaya, Birgit Burkhardt, Marco Zecca, Marie Robin, Peter Bader, Paul Bosman, Antonio M. Risitano, Katharine Patrick, Dirk-Jan Eikema, Edoardo Lanino, Luiz Guilherme Darrigo Junior, Gérard Michel, Vanderson Rocha, Franco Locatelli, Arnold Ganser, Carlo Dufour, Filomena Pierri, Maurizio Miano, Nicolaus Kröger, Abdelghani Tbakhi, Stefano Giardino, Amal Al-Seraihy, Maija Itälä-Remes, Mouhab Ayas, Boris V. Afanasyev, Yves Bertrand, Peter J. Shaw, Régis Peffault de Latour, Martin Bornhäuser, Giardino, S., de Latour, R. P., Aljurf, M., Eikema, D. -J., Bosman, P., Bertrand, Y., Tbakhi, A., Holter, W., Bornhauser, M., Rossig, C., Burkhardt, B., Zecca, M., Afanasyev, B., Michel, G., Ganser, A., Alseraihy, A., Ayas, M., Uckan-Cetinkaya, D., Bruno, B., Patrick, K., Bader, P., Itala-Remes, M., Rocha, V., Jubert, C., Diaz, M. A., Shaw, P. J., Junior, L. G. D., Locatelli, F., Kroger, N., Faraci, M., Pierri, F., Lanino, E., Miano, M., Risitano, A., Robin, M., and Dufour, C.
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Gastroenterology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Fanconi anemia ,Internal medicine ,medicine ,Humans ,Cumulative incidence ,Survival rate ,Retrospective Studies ,Acute leukemia ,Leukemia ,business.industry ,Myelodysplastic syndromes ,Bone marrow failure ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,Allografts ,Survival Rate ,surgical procedures, operative ,Fanconi Anemia ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,leukemia ,stem cell transplantation ,030220 oncology & carcinogenesis ,Myelodysplastic Syndromes ,Acute Disease ,Female ,business ,030215 immunology ,Follow-Up Studies - Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome. The 5-year OS and EFS were 42% (30-53%) and 39% (27-51%), respectively. Patients transplanted in CR showed better OS compared with those transplanted in presence of an active malignant disease (OS:71%[48-95] vs 37% [24-50],P = .04), while none of the other variables considered had an impact. Twenty-two patients received pre-HSCT cytoreduction and 9/22 showed a grade 3-4 toxicity, without any lethal event or negative influence on survival after HSCT(OS:toxicity pre-HSCT 48% [20-75%] vs no-toxicity 51% [25-78%],P = .98). The cumulative incidence of day-100 grade II-IV a-GvHD and of 5-year c-GvHD were 38% (26-50%) and 40% (28-52%). Non-relapse-related mortality and incidence of relapse at 5-years were 40% (29-52%) and 21% (11-30%) respectively, without any significant impact of the tested variables. Causes of death were transplant-related events in most patients (34 out of the 42 deaths, 81%). This analysis confirms the poor outcome of transformed FA patients and identifies the importance of achieving CR pre-HSCT, suggesting that, in a newly diagnosed transformed FA patient, a cytoreductive approach pre-HSCT should be considered if a donor have been secured.
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- 2020
49. African Americans with translocation t(11;14) have superior survival after autologous hematopoietic cell transplantation for multiple myeloma in comparison with Whites in the United States
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Mohamed A. Kharfan-Dabaja, Baldeep Wirk, Hillard M. Lazarus, Nina Shah, Heather Landau, Hemant S. Murthy, Qaiser Bashir, Taiga Nishihori, Kenneth R. Meehan, Nosha Farhadfar, David H. Vesole, Talha Badar, Melhem Solh, Raphael Fraser, Reinhold Munker, Binod Dhakal, Yago Nieto, Jesus G. Berdeja, Cindy Lee, Natalie S. Callander, Parameswaran Hari, Ehsan Malek, Robert A. Kyle, Saurabh Chhabra, Cesar O. Freytes, Shahrukh K. Hashmi, Omar Davila, Sundar Jagannath, Gerhard C. Hildebrandt, Ravi Vij, Shaji Kumar, Miguel Angel Diaz, Siddhartha Ganguly, Rammurti T. Kamble, Anita D'Souza, and Cesar Rodriguez Valdes
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Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Transplantation Conditioning ,Chromosomal translocation ,Transplantation, Autologous ,Article ,Translocation, Genetic ,White People ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,030212 general & internal medicine ,Prospective Studies ,Stage (cooking) ,Multiple myeloma ,Hematopoietic cell ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,medicine.disease ,Confidence interval ,United States ,Transplantation ,Black or African American ,030220 oncology & carcinogenesis ,Female ,business ,Multiple Myeloma - Abstract
Background Multiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard-risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent. Methods This study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187). Results African Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI). Fewer African Americans with t(11;14) (21%) had a coexistent high-risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression-free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT-CI, and receipt of maintenance. Conclusions Race may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.
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- 2020
50. Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era
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Shaji Kumar, Melhem Solh, Lohith S. Bachegowda, Reinhold Munker, Gerhard C. Hildebrandt, Asad Bashey, Muzaffar H. Qazilbash, Yago Nieto, Leona Holmberg, Mohamed A. Kharfan-Dabaja, Nosha Farhadfar, Abraham S. Kanate, Cesar O. Freytes, Saurabh Chhabra, Binod Dhakal, Ruthlee Lu Bayer, Keith Stockerl-Goldstein, Attaphol Pawarode, Qaiser Bashir, Wilson I. Gonsalves, Taiga Nishihori, Sagar S. Patel, Parameswaran Hari, Omar Davila, Shahrukh K. Hashmi, Amer Assal, Jeffrey Schriber, Raphael Fraser, David H. Vesole, Anita D'Souza, Kenneth R. Meehan, Sachiko Seo, Amr Hanbali, Hillard M. Lazarus, Miguel Angel Diaz, Nina Shah, Jean A. Yared, Sherif M. Badawy, Robert Peter Gale, Cindy Lee, Robert F. Cornell, Richard F. Olsson, Yvonne A. Efebera, Hemant S. Murthy, Saulius Girnius, Jan Cerny, and Jesus G. Berdeja
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Transplantation Conditioning ,Graft vs Host Disease ,Transplantation, Autologous ,Article ,Leukemia, Plasma Cell ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Progression-free survival ,Longitudinal Studies ,Aged ,Plasma cell leukemia ,Hematopoietic cell ,Karnofsky Performance Status ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Transplantation ,Leukemia ,surgical procedures, operative ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Cohort study - Abstract
The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4-11%), relapse (REL) 76% (69-82%), progression-free survival (PFS) 17% (13-23%), and overall survival (OS) 28% (22-35%). Karnofsky performance status (KPS) > 90 and ≥very good partial response (VGPR) predicted superior OS in multi-variate analysis for auto-HCT. For allo-HCT, the 4-year outcomes were: NRM 12% (5-21%), REL 69% (56-81%), PFS 19% (10-31%), and OS 31% (19-44%). Compared with prior CIBMTR pPCL patients (1995-2006), inferior survival was noted in the current cohort (3-year OS, 39% vs. 38% in allo-HCT, and 62% vs. 35% in auto-HCT) respectively. However, we noted an increased HCT utilization, from 12% (7-21%) in 1995 to 46% (34-64%) in 2009 using SEER data (available till 2009). Despite modern induction translating to higher proportion receiving HCT, the outcomes remain poor in pPCL patients, mainly derived by high relapse rates post-HCT.
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- 2020
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