1,447 results on '"Unrelated Donor"'
Search Results
2. Reduced human leukocyte antigen mismatching is associated with more favourable outcomes after unrelated donor haematopoietic stem cell transplantation.
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Valatkaite‐Rakstiene, Beatrice, Cekauskiene, Rita, Zvirblis, Tadas, and Jakubauskas, Arturas
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HEMATOPOIETIC stem cell transplantation , *HLA histocompatibility antigens , *CORD blood , *STEM cell donors , *GRAFT versus host disease , *BRAIN death , *ALLELES , *PROGNOSIS - Abstract
The patient–donor human leukocyte antigen (HLA) match remains the most important prognostic factor for successful unrelated donor haematopoietic stem cell transplantation (UD‐HSCT). This single‐centre study comprised 125 adult patients with malignant haematological diseases undergoing their first UD‐HSCT. The primary goal of this study was to validate the impact of HLA matching on HSCT outcomes, specifically at the HLA‐DPB1 and HLA‐DRB3/4/5 loci. A multivariable Cox regression analysis with a backward selection algorithm was employed to assess the associations of selected prognostic factors with outcomes after UD‐HSCT. Any HLA locus mismatch was found to be associated with an increased incidence of grade II–IV acute graft versus host disease (aGvHD) at 100 days (p =.031; hazard ratio [HR] 1.935) and 6 months (p =.004; HR 2.284) after HSCT. The results of the following analyses also confirmed the strong impact of HLA‐DPB1‐only mismatch on the incidence of grade II–IV aGvHD at 100‐day (p =.006; HR 2.642) as well as at 6‐month (p =.007; HR 2.401) time periods. The HLA‐DPB1‐only mismatch was also shown to be statistically significantly associated with lower relapse incidence (p =.034; HR 0.333). The impact of the HLA‐DRB3/4/5 mismatch on outcomes was inconclusive, though the two and more HLA‐DPB1 + DRB3/4/5‐only mismatches showed a trend towards worse outcomes than a single mismatch. Based on our findings and those of more comprehensive studies, the extended HLA loci typing of patients and donors is suggested to avoid unexpected HLA mismatches during the UD selection. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Unrelated or haploidentical allogeneic hematopoietic cell transplantation in second complete remission for acute myeloid leukemia—Improved outcomes over time: A European Society for Blood and Marrow Transplantation Acute Leukemia Working Party study
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Al Hamed, Rama, Ngoya, Maud, Galimard, Jacques‐Emmanuel, Sengeloev, Henrik, Gedde‐Dahl, Tobias, Kulagin, Aleksandr, Platzbecker, Uwe, Yakoub‐Agha, Ibrahim, Byrne, Jenny L., Valerius, Thomas, Socie, Gerard, Kröger, Nicolaus, Blaise, Didier, Bazarbachi, Ali, Sanz, Jaime, Ciceri, Fabio, Nagler, Arnon, and Mohty, Mohamad
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HEMATOPOIETIC stem cell transplantation , *ACUTE myeloid leukemia , *ACUTE leukemia , *TOTAL body irradiation , *BONE marrow - Abstract
Background: Allogeneic hematopoietic cell transplantation (allo‐HCT) is the only cure for acute myeloid leukemia (AML) in second complete remission (CR2). Patients lacking a matched sibling donor (MSD) receive transplants from matched unrelated donors (MUDs), mismatched unrelated donors (MMUDs), haploidentical (haplo) donors, or cord blood. Methods: This is a retrospective, registry‐based European Society for Blood and Marrow Transplantation study that investigates changes in patient‐ and transplant‐related characteristics and posttransplant outcomes over time. Results: We identified 3955 adult patients (46.7% female; median age, 52 years [range, 18–78 years]) with AML in CR2 first transplanted between 2005 and 2019 from a MUD 10/10 (61.4%), MMUD 9/10 (21.9%), or haplo donor (16.7%) and followed for 3.7 years. A total of 725 patients were transplanted between 2005 and 2009, 1600 between 2010 and 2014, and 1630 between 2015 and 2019. Over the three time periods, there was a significant increase in patient age (from 48.7 to 53.5 years; p <.001), use of a haplo donor (from 4.6% to 26.4%; p <.001), and use of posttransplant cyclophosphamide (from 0.4% to 29%; p <.001). There was a significant decrease in total body irradiation and in vivo T‐cell depletion. In multivariate analysis, transplants performed more recently had better outcomes. Leukemia‐free survival (hazard ratio [HR], 0.79; p =.002) and overall survival (HR, 0.73; p <.001) increased over time. Similarly, nonrelapse mortality (HR, 0.64; p <.001) decreased over time. We also observed better graft‐vs‐host disease (GVHD) rates (acute GVHD II–IV: HR, 0.78; p =.03; GVHD‐free, relapse‐free survival: HR, 0.69; p <.001). Conclusions: Even in the absence of an MSD, outcomes of allo‐HCT in CR2 for AML have significantly improved over time, with most favorable outcomes achieved with a MUD. Allogeneic transplantation remains the only curative option for patients with acute myeloid leukemia in second complete remission, with significant changes in patient and transplant characteristics and posttransplant outcomes over time. Even in the absence of matched sibling donors, outcomes have improved over time, with the best outcomes achieved with matched unrelated donors. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Human leukocyte antigen 7/8-matched unrelated bone marrow transplantation using anti-thymocyte globulin in children.
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Hamada, Motoharu, Muramatsu, Hideki, Torii, Yuka, Suzuki, Kyogo, Narita, Atsushi, Yoshida, Taro, Imaya, Masayuki, Yamamori, Ayako, Wakamatsu, Manabu, Miwata, Shunsuke, Narita, Kotaro, Kataoka, Shinsuke, Kawashima, Nozomu, Taniguchi, Rieko, Nishikawa, Eri, Nishio, Nobuhiro, Ito, Yoshinori, Kojima, Seiji, and Takahashi, Yoshiyuki
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Human leukocyte antigen (HLA) mismatched unrelated donor transplantation is associated with an increased risk of graft-versus-host disease, graft failure, and infection, which increases post-transplant morbidity and mortality. In this single-center retrospective study, outcomes were evaluated in 30 consecutive children who underwent bone marrow transplantation (BMT) from HLA 1 allele-mismatched (HLA 7/8-matched) unrelated donors with rabbit anti-thymocyte globulin (rATG) as graft-versus-host disease (GVHD) prophylaxis. The 3-year overall survival (OS), event-free survival (EFS), and GVHD-relapse-free survival rates were 91.7% (95% CI 70.5%–91.9%), 88.3% (95% CI 67.5%–96.1%), and 73.9% (95% CI 52.4%–86.8%), respectively. Grade II–IV and III–IV acute GVHD occurred in 10 (33%) and 2 (7.0%) patients, respectively. The 3-year cumulative incidence of chronic GVHD was 7.8%. No fatal viral infections occurred. The study results show the feasibility of HLA 7/8-matched unrelated BMT with ATG to achieve favorable outcomes and acceptable GVHD, especially for patients who lack a fully matched donor. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post‐transplant cyclophosphamide in AML in first complete remission.
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Nagler, Arnon, Labopin, Myriam, Dholaria, Bhagirathbhai, Blaise, Didier, Bondarenko, Sergey, Vydra, Jan, Choi, Goda, Rovira, Montserrat, Reményi, Péter, Meijer, Ellen, Bulabois, Claude Eric, Diez‐Martin, J. L., Yakoub‐Agha, Ibrahim, Brissot, Eolia, Spyridonidis, Alexandros, Sanz, Jaime, Patel, Amit, Arat, Mutlu, Bazarbachi, Ali, and Bug, Gesine
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CELL transplantation , *ACUTE myeloid leukemia , *CYCLOPHOSPHAMIDE , *MULTIVARIATE analysis , *OVERALL survival - Abstract
Summary: Pre‐transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo‐HCT). The impact of MRD on the outcomes of post‐transplant cyclophosphamide (PTCy)‐based allo‐HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow‐up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2‐year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia‐free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD‐free, relapse‐free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non‐relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo‐HCT with PTCy, pre‐transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Outcomes of patients with hematological malignancies who undergo unrelated donor hematopoietic stem cell transplantation with ATG-Fresenius versus ATG-Genzyme.
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Wang, Lu, Kong, Peiyan, Zhang, Cheng, Gao, Li, Zhu, Lidan, Liu, Jia, Gao, Shichun, Chen, Ting, Liu, Huanfeng, Yao, Han, Liu, Yuqing, Feng, Yimei, Zhao, Lu, Li, Yuxia, Gao, Lei, and Zhang, Xi
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STEM cell transplantation , *HEMATOPOIETIC stem cell transplantation , *STEM cell donors , *HEMATOLOGIC malignancies , *GRAFT versus host disease - Abstract
To compare the outcomes of patients with hematological malignancies who received ATG-Fresenius (ATG-F) 20 mg/kg versus those who received ATG-Genzyme (ATG-G) 10 mg/kg in an unrelated donor hematopoietic stem cell transplantation (HSCT) procedure, a total of 186 patients who underwent their first allogeneic HSCT with an unrelated donor were retrospectively analyzed. One hundred and seven patients received ATG-F, and seventy-nine patients received ATG-G. Multivariate analysis showed that the type of ATG preparation had no effect on neutrophil engraftment (P = 0.61), cumulative incidence of relapse (P = 0.092), nonrelapse mortality (P = 0.44), grade II-IV acute graft-versus-host disease (GVHD) (P = 0.47), chronic GVHD (P = 0.29), overall survival (P = 0.795), recurrence-free survival (P = 0.945) or GVHD-free relapse-free survival (P = 0.082). ATG-G was associated with a lower risk of extensive chronic GVHD and a higher risk of cytomegaloviremia (P = 0.01 and HR = 0.41, P < 0.001 and HR = 4.244, respectively). The results of this study suggest that the preparation of rabbit ATG used for unrelated HSCT should be selected based on the incidence of extensive chronic GVHD of each center, and the posttransplant management strategy should be adjusted according to the ATG preparation. [ABSTRACT FROM AUTHOR]
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- 2023
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7. Unrelated Donor Allogeneic Transplant
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Chhabra, Saurabh, Hari, Parameswaran, Radhakrishnan, Vivek, Section editor, Doria, Cataldo, Series Editor, Chandy, Mammen, editor, Radhakrishnan, Vivek S., editor, and Sukumaran, Reghu K., editor
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- 2021
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8. Unrelated Donor Transplantation in Children with Thalassemia using Reduced-Intensity Conditioning: The URTH Trial
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Shenoy, Shalini, Walters, Mark C, Ngwube, Alex, Soni, Sandeep, Jacobsohn, David, Chaudhury, Sonali, Grimley, Michael, Chan, Kawah, Haight, Ann, Kasow, Kimberley A, Parikh, Suhag, Andreansky, Martin, Connelly, Jim, Delgado, David, Godder, Kamar, Hale, Gregory, Nieder, Michael, Pulsipher, Michael A, Trachtenberg, Felicia, Neufeld, Ellis, Kwiatkowski, Janet L, and Thompson, Alexis A
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Immunology ,Rare Diseases ,Pediatric ,Clinical Trials and Supportive Activities ,Regenerative Medicine ,Clinical Research ,Transplantation ,Stem Cell Research ,Hematology ,Stem Cell Research - Nonembryonic - Human ,Good Health and Well Being ,Adolescent ,Bone Marrow Transplantation ,Child ,Child ,Preschool ,Female ,Fetal Blood ,Graft vs Host Disease ,Hematopoietic Stem Cell Transplantation ,Humans ,Infant ,Infections ,Male ,Survival Analysis ,Thalassemia ,Transplantation Conditioning ,Transplantation ,Homologous ,Treatment Outcome ,Unrelated Donors ,Hematopoietic stem cell transplant ,Reduced-intensity conditioning ,Unrelated donor ,Clinical Sciences ,Cardiovascular medicine and haematology - Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion-dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in children with TDT. Thirty-three children, ages 1 to 17 years, received bone marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234) after BM and UCB allografts, respectively. With a median follow-up of 58 months (range, 7 to 79), overall and thalassemia-free survival was 82% (95% CI, .64% to .92%) and 79% (95% CI, .6% to .9%), respectively. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB allografts was 24% and 44%; the 2-year cumulative incidence of chronic extensive GVHD was 29% and 21%, respectively; 71% of BM and 91% of UCB recipients discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33 patients. Efforts to reduce GVHD and infectious complications are being pursued further.
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- 2018
9. Neither COVID-19, nor cryopreservation, prevented allogeneic product infusion: A report from the National Marrow Donor Program.
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Farhadfar, Nosha, Newman, Jeni, Novakovich, Jennifer, Barten, Jacklyn, Ndifon, Eric T., Oakes, Jason, Cody, Meghann, Pham, Huy P., Auletta, Jeffery J., Miller, John P., Devine, Steven M., and Stefanski, Heather E.
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COVID-19 ,BONE marrow ,CRYOPRESERVATION of cells ,COVID-19 pandemic ,STEM cell donors - Abstract
Background: The Coronavirus Disease 2019 (COVID-19) pandemic in early 2020 has resulted in an unprecedented level of uncertainty and challenge for the stem cell donor registries. To address these challenges, rapid strategies were implemented by the National Marrow Donor Registry (NMDP) and its network partners. Herein, we aim to report the impact of the COVID-19 pandemic on the collection, utilization of grafts, and short-term outcomes of patients who received stem cell products from COVID-19-positive donors. Methods: NMDP data during the early phase (1 March 2020 through 1 May 2020) of the pandemic were compared to the later phase (1 March 2021 through 1 May 2021). Odds ratios were calculated to determine the impact of the pandemic on graft sources requested by transplant centers (TCs). The Kruskal-Wallis test was used to test the effect of the pandemic on the disease indication, volume of searches, and number of products not infused. Results: Although there was an initial decline in overall donor searches during the early phase of the pandemic, these numbers increased reaching prepandemic levels during the later phase. Urgent malignant diseases remained the most common indication for transplant in 2021. The pandemic necessitated cryopreservation of stem cell products due to transportation restrictions as well as clinical uncertainties in managing the virus. Cryopreserved grafts remained the most common requested grafts throughout the pandemic. In the later phase of the pandemic, the total numbers of requests for fresh grafts increased, mostly due to the increase in requests for fresh bone marrow (BM) grafts. As the pandemic continued, TCs became more accepting of cryopreservation, resulting in a reduction in the number of products not infused. Lastly, no short-term deleterious outcomes were noted among the patients who had stem cell products infused from a SARS-CoV-2-positive donor. Conclusion: Throughout the pandemic, the NMDP and TCs worked tirelessly to ensure that patients would receive lifesaving grafts when needed. The data reported here, although limited by small numbers, illustrate that transplantation from donors with COVID-19 is feasible and safe. [ABSTRACT FROM AUTHOR]
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- 2022
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10. Demand and usage of unrelated donor products for allogeneic haematopoietic cell transplantation during the COVID‐19 pandemic: A Canadian Blood Services Stem Cell Registry analysis.
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Allan, David S., Green, Meagan, Morris, Gail, Weiss, Jason, Dibdin, Nicholas, Mercer, Dena, and Seftel, Matthew
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CELL transplantation , *COVID-19 pandemic , *CELL analysis , *STEM cells , *CHILD patients - Abstract
Background and Objectives: Understanding changes in the demand and usage of unrelated allogeneic haematopoietic cell transplantation (HCT) donors during the COVID‐19 pandemic is needed to optimize pandemic preparedness of registry and donor collection services. The aim of this study was to understand the extent to which the pandemic has impacted the demand and usage of unrelated donors and cord blood units (CBUs) at Canadian Blood Services (CBS). Materials and Methods: Data regarding stem cell donor interest and product usage for unrelated allogeneic HCT were retrieved from the database at CBS using de‐identified anonymous information. Results: Unrelated donor searches for Canadian patients remained unchanged by the pandemic, reflecting stable demand. The number of unrelated allogeneic transplants performed within Canada also remained stable, while the number of cord blood transplants increased, chiefly for paediatric patients. Requests for donor verification typing, a first signal of potential interest, increased from domestic centres during the first 6 months of the pandemic and decreased from international centres, before returning to baseline levels. The proportion of transplants for Canadian patients who used stem cell products procured from Canadian donors increased between 3 and 6 months after the start of the pandemic before returning to baseline and appears to be increasing again more than 1 year after the start of the pandemic. Use of CBUs for Canadian paediatric patients increased and remains elevated. Conclusion: Demand for unrelated adult HCT donors has remained stable despite the evolving pandemic with a transient and recurring increased interest and usage of domestic adult donors. Use of CBUs for paediatric patients has increased and remains elevated. Registries and donor collection centres should maintain the capacity to expand services for domestic donor collection during pandemics to offset threats to international donor usage. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Superior survival after unrelated allogeneic stem cell transplantation with low-dose ATG compared to low-dose TBI in myeloablative fludarabine/busulfan-based regimen for MDS on behalf of the adult MDS Working Group of the JSTCT.
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Fujioka M, Itonaga H, Nakazawa H, Nishida T, Kataoka K, Ikeda T, Kako S, Matsuoka KI, Adachi K, Fujiwara SC, Aotsuka N, Kawakita T, Sakaida E, Kanda Y, Ichinohe T, Atsuta Y, Miyazaki Y, and Ishiyama K
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The fludarabine/intravenous busulfan 12.8 mg/kg (FB4) regimen is an effective conditioning regimen in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome (MDS); however, limited data is available on the prognostic impact of FB4 with low-dose anti-thymoglobulin (ATG ≤ 5 mg/kg) or low-dose total body irradiation (TBI ≤ 4 Gy). Therefore, we retrospectively evaluated the outcomes in 280 adults with de novo MDS who underwent their first transplantation from an unrelated donor between 2009 and 2018. Median age was 61 years (range, 16 to 70 years). In the FB4 alone (FB4), FB4 plus ATG (FB4-ATG), and FB4 plus TBI (FB4-TBI) groups, 3-year overall survival (OS) rates were 39.9, 64.8, and 43.7 %; 3-year non-relapse mortality (NRM) were 32.1, 22.1, and 27.1%; and 3-year relapse incidences were 34.7, 21.2, and 28.9%, respectively. The multivariate analyses showed that FB4-ATG group significantly correlated with better OS (hazard Ratio [HR], 0.51; 95% confidence interval [CI], 0.27-0.95; P=0.032) than FB4 group. FB4-ATG group tended to correlate with lower NRM (HR, 0.36;95% CI, 0.13-1.06; P=0.063) than FB4 group. In comparison with FB4-TBI group, FB4-ATG group showed better OS (HR 0.52, 95% CI 0.27-0.99, P=0.049) and NRM (HR 0.034, 95% CI 0.11-0.92, P=0.034). No significant differences were observed in OS and NRM between the FB4-TBI and FB4 groups. The present study demonstrated that the FB4 plus low-dose ATG regimen improved OS and NRM, but FB4 plus low-dose TBI regimen had no clear benefit over FB4 alone, in MDS patients who used unrelated donors., Competing Interests: Declaration of competing interest Y. Miyazaki received honoraria from Novartis Pharma, Nippon-Shinyaku Co., Sumitomo Dainippon Pharma, Astellas Pharma and Celgene Co., Chugai Pharma, AbbiVie GK, and SymBio Pharmaceuticals, and funding from Sumitomo Dainippon Pharma for research and Chugai Pharma for scholarships., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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12. Denovo granulocyte-macrophage colony-stimulating factor antibody production has been linked to acute graft-versus-host disease following hematopoietic stem cell transplantation from an HLA-matched, unrelated donor.
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Valatkaite-Rakstiene B, Cekauskiene R, and Jakubauskas A
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The role of non-HLA antibodies in hematopoietic stem cell transplantation (HSCT) and acute graft-versus-host disease (aGVHD) is not established. Serum samples collected from 58 adult patients before and after HSCT were examined for non-HLA antibodies. Following HSCT, 47 out of 58 patients (81.0 %) had various antibody patterns, with 23 of them (39.7 %) producing denovo antibodies. The most prevalent antibodies were directed against granulocyte-macrophage colony-stimulating factor (GM-CSF). The Fisher exact test revealed a statistically significant correlation between the incidence of acute graft-versus-host disease and denovo production of GM-CSF antibodies in patients fully HLA-matched with their donors (p = 0.001). There were no cases of denovo GM-CSF antibody production seen in non-permissively HLA-mismatched patients. Consequently, we hypothesize that the development of aGVHD after HLA-matched HSCT may differ from that following HLA-mismatched HSCT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)
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- 2024
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13. Neither COVID-19, nor cryopreservation, prevented allogeneic product infusion: A report from the National Marrow Donor Program
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Nosha Farhadfar, Jeni Newman, Jennifer Novakovich, Jacklyn Barten, Eric T. Ndifon, Jason Oakes, Meghann Cody, Huy P. Pham, Jeffery J. Auletta, John P. Miller, Steven M. Devine, and Heather E. Stefanski
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COVID-19 ,donor registry ,unrelated donor ,hematopoietic stem cells ,National Marrow Donor Program ,SARS-CoV-2 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic in early 2020 has resulted in an unprecedented level of uncertainty and challenge for the stem cell donor registries. To address these challenges, rapid strategies were implemented by the National Marrow Donor Registry (NMDP) and its network partners. Herein, we aim to report the impact of the COVID-19 pandemic on the collection, utilization of grafts, and short-term outcomes of patients who received stem cell products from COVID-19-positive donors.MethodsNMDP data during the early phase (1 March 2020 through 1 May 2020) of the pandemic were compared to the later phase (1 March 2021 through 1 May 2021). Odds ratios were calculated to determine the impact of the pandemic on graft sources requested by transplant centers (TCs). The Kruskal–Wallis test was used to test the effect of the pandemic on the disease indication, volume of searches, and number of products not infused.ResultsAlthough there was an initial decline in overall donor searches during the early phase of the pandemic, these numbers increased reaching pre-pandemic levels during the later phase. Urgent malignant diseases remained the most common indication for transplant in 2021. The pandemic necessitated cryopreservation of stem cell products due to transportation restrictions as well as clinical uncertainties in managing the virus. Cryopreserved grafts remained the most common requested grafts throughout the pandemic. In the later phase of the pandemic, the total numbers of requests for fresh grafts increased, mostly due to the increase in requests for fresh bone marrow (BM) grafts. As the pandemic continued, TCs became more accepting of cryopreservation, resulting in a reduction in the number of products not infused. Lastly, no short-term deleterious outcomes were noted among the patients who had stem cell products infused from a SARS-CoV-2-positive donor.ConclusionThroughout the pandemic, the NMDP and TCs worked tirelessly to ensure that patients would receive lifesaving grafts when needed. The data reported here, although limited by small numbers, illustrate that transplantation from donors with COVID-19 is feasible and safe.
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- 2022
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14. Transplantation using targeted busulfan for Diamond–Blackfan anemia.
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Kato, Shota, Nakano, Yoshiko, Hidaka, Moe, Sekiguchi, Masahiro, Watanabe, Kentaro, Fujimura, Junya, and Kato, Motohiro
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APLASTIC anemia treatment , *GANCICLOVIR , *HLA-B27 antigen , *INTRAVENOUS therapy , *BONE marrow transplantation , *APLASTIC anemia , *FERRITIN , *TREATMENT effectiveness , *BUSULFAN , *HEMATOPOIETIC stem cell transplantation , *RADIOTHERAPY , *ROUTINE diagnostic tests - Abstract
The article presents a case study of a three year old with Diamond–Blackfan anemia (DBA) who underwent allogeneic hematopoietic cell transplantation (HCT). It is reported that the patient received reduced-intensity conditioning with targeted busulfan. It is further reported that the patient achieved successful engraftment, became transfusion-independent, and showed no severe adverse events during the 12-month follow-up.
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- 2023
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15. Post-transplantation cyclophosphamide versus conventional graft-versus-host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation.
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Mehta, Rohtesh, Saliba, Rima, Chen, Julianne, Rondon, Gabriela, Hammerstrom, Aimee, Alousi, Amin, Qazilbash, Muzaffar, Bashir, Qaiser, Ahmed, Sairah, Popat, Uday, Hosing, Chitra, Khouri, Issa, Shpall, Elizabeth, Champlin, Richard, and Ciurea, Stefan
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GVHD ,HLA-mismatched transplantation ,MMUD ,post transplantation cyclophosphamide ,unrelated donor ,Adult ,Aged ,Cyclophosphamide ,Female ,Graft Survival ,Graft vs Host Disease ,Hematopoietic Stem Cell Transplantation ,Histocompatibility ,Humans ,Male ,Middle Aged ,Mycophenolic Acid ,Premedication ,Retrospective Studies ,Tacrolimus ,Unrelated Donors ,Young Adult - Abstract
Post-transplantation cyclophosphamide (PTCy) is an effective strategy to prevent graft-versus-host disease (GVHD) after haploidentical haematopoietic cell transplantation (HCT). We determined the efficacy of PTCy-based GVHD prophylaxis in human leucocyte antigen (HLA)-mismatched unrelated donor (MMUD) HCT. We analysed 113 adult patients with high-risk haematological malignancies who underwent one-antigen MMUD transplantation between 2009 and 2013. Of these, 41 patients received PTCy, tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis; 72 patients received conventional prophylaxis with anti-thymocyte globulin, tacrolimus and methotrexate. Graft source was primarily bone marrow (83% PTCy vs. 63% conventional group). Incidence of grade II-IV (37% vs. 36%, P = 0·8) and grade III-IV (17% vs. 12%, P = 0·5) acute GVHD was similar at day 100. However, the incidence of grade II-IV acute GVHD by day 30 was significantly lower in the PTCy group (0% vs. 15%, P = 0·01). Median time to neutrophil (18 days vs. 12 days, P
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- 2016
16. Corrigendum: Haplotype Motif-Based Models for KIR-Genotype Informed Selection of Hematopoietic Cell Donors Fail to Predict Outcome of Patients With Myelodysplastic Syndromes or Secondary Acute Myeloid Leukemia
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Johannes Schetelig, Henning Baldauf, Linda Koster, Michelle Kuxhausen, Falk Heidenreich, Liesbeth C. de Wreede, Stephen Spellman, Michel van Gelder, Benedetto Bruno, Francesco Onida, Vinzenz Lange, Carolin Massalski, Victoria Potter, Per Ljungman, Nicolaas Schaap, Patrick Hayden, Stephanie J. Lee, Nicolaus Kröger, Kathy Hsu, Alexander H. Schmidt, Ibrahim Yakoub-Agha, and Marie Robin
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KIR ,KIR2DS1 ,KIR3DL1 ,hematopoietic stem cell transplantation ,donor selection ,unrelated donor ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2021
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17. Improving Unrelated Donor Equity: Assessing Mismatched Donor Opportunities with Real-World Data in a Minority-Predominant Cohort.
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Hammami MB, Verceles JA, Goldfinger M, Shah N, Sica RA, Mantzaris I, Kornblum N, Konopleva M, Shastri A, Shapiro LC, Feldman EJ, Gritsman K, Verma A, and Cooper DL
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- Humans, Female, Male, Middle Aged, Adult, Graft vs Host Disease prevention & control, Minority Groups statistics & numerical data, Cohort Studies, HLA Antigens immunology, Aged, Unrelated Donors, Hematopoietic Stem Cell Transplantation statistics & numerical data, Histocompatibility Testing
- Abstract
Recent advances in graft-versus-host disease (GVHD) prophylaxis including post-transplant cyclophosphamide (PTCy) and abatacept have significantly improved outcomes following HLA-mismatched allogenic hematopoietic stem cell transplantation (allo-HSCT) and have tremendous potential for reducing racial disparities in donor availability. A recent small study employing bone marrow as the source of stem cells showed similar outcomes after 5/8 versus 7/8 matches and is currently being tested in a larger study using peripheral blood stem cells. In this study, we examine real-world alternative donor HSCT options for a minority-predominant cohort in the Bronx, NY, focusing on the availability of lesser-matched (5/8 to 7/8) donors. Records of patients who underwent HLA typing at Montefiore Medical Center (2019 to 2022) were reviewed. The National Marrow Donor Program registry was queried to evaluate the availability of donors with at least 99% likelihood of HLA match at various levels (5/8, 6/8, 7/8, 8/8). Two hundred forty-one patients were included, 70% were non-White. Although the availability of ≥7/8 donors was less common in non-White patients, 100% of patients from each group had at least one or more 5/8 and 6/8 HLA-matched donors and more than 80% of these patients had >100 potential 5/8 and 6/8 HLA-matched donors. There was no statistical difference by race or ethnicity in the mean number of donors at 5/8 and 6/8 HLA-match levels. We demonstrate through real-world data that patients from diverse ethnic and racial backgrounds have access to 5/8 and 6/8 HLA-matched donors for allo-HSCT, potentially eliminating disparities in donor availability and allowing prioritization of other donor selection characteristics such as donor age, sex, ABO, and B leader matching. Further work is needed to study whether the use of mismatched donors offers a more potent graft-versus malignancy effect and optimal GVHD prophylaxis., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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18. Preparing the Patient for HSCT: Conditioning Regimens and Their Scientific Rationale
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Kitko, Carrie-Lynn, Gatwood, Katie, Connelly, James, and Brown, Valerie I., editor
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- 2018
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19. Chronic GvHD
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Shapiro, Terry Wikle, Kapadia, Malika, and Brown, Valerie I., editor
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- 2018
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20. How to Select a Donor and Hematopoietic Stem Cell Source: Related Versus Unrelated Donors for Allogeneic HSCT
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Kapadia, Malika, Greiner, Robert, and Brown, Valerie I., editor
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- 2018
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21. Unrelated Donor Hematopoietic Stem Cell Transplantation for Sickle Cell Disease
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Ngwube, Alexander, Shenoy, Shalini, Meier, Emily Riehm, editor, Abraham, Allistair, editor, and Fasano, Ross M., editor
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- 2018
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22. Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post-transplant cyclophosphamide in AML in first complete remission
- Author
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Arnon Nagler, Myriam Labopin, Bhagirathbhai Dholaria, Didier Blaise, Sergey Bondarenko, Jan Vydra, Goda Choi, Montserrat Rovira, Péter Reményi, Ellen Meijer, Claude Eric Bulabois, J. L. Diez‐Martin, Ibrahim Yakoub‐Agha, Eolia Brissot, Alexandros Spyridonidis, Jaime Sanz, Amit Patel, Mutlu Arat, Ali Bazarbachi, Gesine Bug, Bipin N. Savani, Sebastian Giebel, Fabio Ciceri, Mohamad Mohty, Hematology, AII - Inflammatory diseases, CCA - Cancer Treatment and quality of life, and CCA - Imaging and biomarkers
- Subjects
measurable residual disease ,allogeneic haematopoietic cell transplantation ,post-transplant cyclophosphamide ,unrelated donor ,acute myeloid leukaemia ,Hematology - Abstract
Pre-transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo-HCT). The impact of MRD on the outcomes of post-transplant cyclophosphamide (PTCy)-based allo-HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow-up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2-year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia-free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD-free, relapse-free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non-relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo-HCT with PTCy, pre-transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.
- Published
- 2023
23. Cord Blood Transplants Versus Other Sources of Allografts: Comparison of Data in Adult Setting
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Mehta, Rohtesh S., Brunstein, Claudio G., Abutalib, Syed A., Series editor, Armitage, James O., Series editor, Horwitz, Mitchell, editor, and Chao, Nelson, editor
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- 2017
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24. Haplotype Motif-Based Models for KIR-Genotype Informed Selection of Hematopoietic Cell Donors Fail to Predict Outcome of Patients With Myelodysplastic Syndromes or Secondary Acute Myeloid Leukemia
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Johannes Schetelig, Henning Baldauf, Linda Koster, Michelle Kuxhausen, Falk Heidenreich, Liesbeth C. de Wreede, Stephen Spellman, Michel van Gelder, Benedetto Bruno, Francesco Onida, Vinzenz Lange, Carolin Massalski, Victoria Potter, Per Ljungman, Nicolaas Schaap, Patrick Hayden, Stephanie J. Lee, Nicolaus Kröger, Kathy Hsu, Alexander H. Schmidt, Ibrahim Yakoub-Agha, and Marie Robin
- Subjects
KIR ,KIR2DS1 ,KIR3DL1 ,hematopoietic stem cell transplantation ,donor selection ,unrelated donor ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Results from registry studies suggest that harnessing Natural Killer (NK) cell reactivity mediated through Killer cell Immunoglobulin-like Receptors (KIR) could reduce the risk of relapse after allogeneic Hematopoietic Cell Transplantation (HCT). Several competing models have been developed to classify donors as KIR-advantageous or disadvantageous. Basically, these models differ by grouping donors based on distinct KIR–KIR–ligand combinations or by haplotype motif assignment. This study aimed to validate different models for unrelated donor selection for patients with Myelodysplatic Syndromes (MDS) or secondary Acute Myeloid Leukemia (sAML). In a joint retrospective study of the European Society for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) registry data from 1704 patients with secondary AML or MDS were analysed. The cohort consisted mainly of older patients (median age 61 years) with high risk disease who had received chemotherapy-based reduced intensity conditioning and anti-thymocyte globulin prior to allogeneic HCT from well-matched unrelated stem cell donors. The impact of the predictors on Overall Survival (OS) and relapse incidence was tested in Cox regression models adjusted for patient age, a modified disease risk index, performance status, donor age, HLA-match, sex-match, CMV-match, conditioning intensity, type of T-cell depletion and graft type. KIR genes were typed using high-resolution amplicon-based next generation sequencing. In univariable and multivariable analyses none of the models predicted OS and the risk of relapse consistently. Our results do not support the hypothesis that optimizing NK-mediated alloreactivity is possible by KIR-genotype informed selection of HLA-matched unrelated donors. However, in the context of allogeneic transplantation, NK-cell biology is complex and only partly understood. KIR-genes are highly diverse and current assignment of haplotype motifs based on the presence or absence of selected KIR genes is over-simplistic. As a consequence, further research is highly warranted and should integrate cutting edge knowledge on KIR genetics, and NK-cell biology into future studies focused on homogeneous groups of patients and treatment modalities.
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- 2021
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25. Haplotype Motif-Based Models for KIR-Genotype Informed Selection of Hematopoietic Cell Donors Fail to Predict Outcome of Patients With Myelodysplastic Syndromes or Secondary Acute Myeloid Leukemia.
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Schetelig, Johannes, Baldauf, Henning, Koster, Linda, Kuxhausen, Michelle, Heidenreich, Falk, de Wreede, Liesbeth C., Spellman, Stephen, van Gelder, Michel, Bruno, Benedetto, Onida, Francesco, Lange, Vinzenz, Massalski, Carolin, Potter, Victoria, Ljungman, Per, Schaap, Nicolaas, Hayden, Patrick, Lee, Stephanie J., Kröger, Nicolaus, Hsu, Kathy, and Schmidt, Alexander H.
- Subjects
ACUTE myeloid leukemia ,MYELODYSPLASTIC syndromes ,KILLER cell receptors ,STEM cell donors ,OLDER patients ,AUTOIMMUNE hemolytic anemia - Abstract
Results from registry studies suggest that harnessing Natural Killer (NK) cell reactivity mediated through Killer cell Immunoglobulin-like Receptors (KIR) could reduce the risk of relapse after allogeneic Hematopoietic Cell Transplantation (HCT). Several competing models have been developed to classify donors as KIR-advantageous or disadvantageous. Basically, these models differ by grouping donors based on distinct KIR–KIR–ligand combinations or by haplotype motif assignment. This study aimed to validate different models for unrelated donor selection for patients with Myelodysplatic Syndromes (MDS) or secondary Acute Myeloid Leukemia (sAML). In a joint retrospective study of the European Society for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) registry data from 1704 patients with secondary AML or MDS were analysed. The cohort consisted mainly of older patients (median age 61 years) with high risk disease who had received chemotherapy-based reduced intensity conditioning and anti-thymocyte globulin prior to allogeneic HCT from well-matched unrelated stem cell donors. The impact of the predictors on Overall Survival (OS) and relapse incidence was tested in Cox regression models adjusted for patient age, a modified disease risk index, performance status, donor age, HLA-match, sex-match, CMV-match, conditioning intensity, type of T-cell depletion and graft type. KIR genes were typed using high-resolution amplicon-based next generation sequencing. In univariable and multivariable analyses none of the models predicted OS and the risk of relapse consistently. Our results do not support the hypothesis that optimizing NK-mediated alloreactivity is possible by KIR-genotype informed selection of HLA-matched unrelated donors. However, in the context of allogeneic transplantation, NK-cell biology is complex and only partly understood. KIR-genes are highly diverse and current assignment of haplotype motifs based on the presence or absence of selected KIR genes is over-simplistic. As a consequence, further research is highly warranted and should integrate cutting edge knowledge on KIR genetics, and NK-cell biology into future studies focused on homogeneous groups of patients and treatment modalities. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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26. The Adverse Event Landscape of Stem Cell Transplant: Evidence for aGVHD Driving Early Transplant Associated Toxicities.
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Takahashi T, Watkins B, Bratrude B, Neuberg D, Hebert K, Betz K, Yu A, Choi SW, Davis J, Duncan C, Giller R, Grimley M, Harris AC, Jacobsohn D, Lalefar N, Farhadfar N, Pulsipher MA, Shenoy S, Petrovic A, Schultz KR, Yanik GA, Blazar BR, Horan JT, Langston A, Kean LS, and Qayed M
- Abstract
Although unrelated-donor (URD) hematopoietic cell transplantation (HCT) is associated with many toxicities, a detailed analysis of adverse events, as defined by the Common Terminology Criteria for Adverse Events (CTCAE), has not previously been curated. This represents a major unmet need, especially as it relates to assessing the safety of novel agents. We analyzed a detailed AE database from the "ABA2" randomized, double-blind, placebo-controlled clinical trial of abatacept for acute graft-versus-host disease (aGVHD) prevention, for which the FDA mandated a detailed AE assessment through Day +180, and weekly neutrophil and platelet counts through Day +100. These were analyzed for their relationship to key transplant outcomes, with a major focus on the impact of aGVHD on the development/severity of AEs. A total of 2102 AEs and 1816 neutrophil/platelet counts were analyzed from 142 8/8-HLA-matched URD HCT recipients on ABA2 (placebo cohort, n = 69, abatacept cohort, n = 73). This analysis resulted in 2 major observations. (1) Among graft source, conditioning intensity, age, and Grade 2 to 4 aGVHD, only aGVHD impacted Grade 3 to 5 AE acquisition after the first month post-transplant. (2) The development of Grade 3 to 4 aGVHD was associated with thrombocytopenia. We have created a detailed resource for the transplant community by which to contextualize clinical toxicities after transplant. It has identified aGVHD as a major driver of post-HCT Grade 3 to 5 AEs, and underscored a link between aGVHD and thrombocytopenia. This establishes a critical safety framework upon which the impact of novel post-transplant aGVHD therapeutics should be evaluated. This trial was registered at www.clinicaltrials.gov (#NCT01743131)., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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27. Severe Acute Respiratory Syndrome Coronavirus-2 Pandemia: Facts and Perspectives in a Bone Marrow Transplant Unit
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Michele Malagola, Nicola Polverelli, Lisa Gandolfi, Tatiana Zollner, Simona Bernardi, Camilla Zanaglio, Federica Re, Enrico Morello, Alessandro Turra, Alessandro Isidori, and Domenico Russo
- Subjects
allogeneic stem cell transplanation ,COVID 19 ,donor search algorithm ,haploidentical donor ,unrelated donor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2020
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28. IMPACT OF HLA-DPB1 INCOMPATIBILITY ON THE RESULTS OF ALLOGENEIC HEMATOPOIETIC STEM CELLS TRANSPLANTATION FROM HLA-A-B-C–DRB1-DQB1-COMPATIBLE UNRELATED DONOR
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E. G. Khamaganova, Е. N. Parovichnikova, L. A. Kuzmina, S. М. Kulikov, E. Р. Kuzminova, R. S. Chapova, and V. G. Savchenko
- Subjects
allo-hsct ,unrelated donor ,gvhd ,hla-dpb1 ,compatibility ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Introduction. An accepted fact in allogeneic hematopoietic stem cells transplantation (allo-HSCT) from unrelated donors is that matching for HLA genes is critical to ensure the best outcomes for patients. The current gold standard is an unrelated donor matched for 10/10 HLA alleles (HLA-A, -B, -C, -DRB1, -DQB1). In the HLA-mismatched setting graft-versus-host disease (GVHD) is increased, and overall survival becomes significantly worse. The importance of HLA-DPB1matching is more controversial.The aim of our study was to evaluate the impact of HLA-DPB1 mismatches on outcome of patients who underwent 10/10 HLA matched unrelated HSCT.Materials and methods. 49 patients treated with allo-HSCT in transplant center of National Research Center for Hematology from 10/10 HLA-matched unrelated donors were included in the study. High-resolution typing for HLA-DPB1 was done by PCR with sequence specific primers (SSP) using Olerup typing kits. HLA-DPB1 permissive/nonpermissive mismatches were examined according to TCE groups. Overall survival, event-free survival and survival without acute graft-versus-host disease were calculated by Kaplan–Meier method, and compared with log-rank test. Proportional hazard Cox models were used for multivariate analysis.Results. The 3-year overall survival after allo-HSCT was 68 %, event-free survival – 51 %, acute GVHD-free survival – 62 %. No significant impacts of HLA-DPB1 disparities on overall, event-free survival and probability of acute graft-versus-host disease were observed. Patients with nonpermissive HLA-DPB1-incompatible donors had a tendency to increased event-free survival. The factors significantly increasing risk of acute GVHD were peripheral blood grafts, advanced-stage disease and male gender of recipients.Conclusion. The factors associated with acute GVHD are peripheral blood grafts, advanced-stage disease and male sex of recipients. For more precise evaluation of impact of HLA-DPB1-incompatibility on results of allo-HSCT further investigations are needed.
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- 2018
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29. Janus kinase 2 V617F mutation in an unrelated peripheral blood stem cell donor
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Shang-Hsien Yang, Hsiang-Lin Wan, Ming-Hui Gu, and Tso-Fu Wang
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Granulocyte colony-stimulating factor ,Janus kinase 2 V617F mutation ,Peripheral blood stem cell harvest ,Polycythemia vera ,Unrelated donor ,Medicine - Abstract
Polycythemia vera (PV) is relatively uncommon in early adulthood, and evidence about the prevalence of the Janus kinase 2 (JAK2) V617F mutation in the general population is limited. Here, we report a previously healthy volunteer peripheral blood stem cell (PBSC) donor who developed symptomatic PV with the JAK2 V617F mutation 2 years after PBSC mobilization and harvest. The characteristic mutation was identified retrospectively in the blood sample of the donor at the confirmation typing stage, which was before granulocyte colony-stimulating factor injection. This report presents a safety issue for both donor and recipient of hematopoietic stem cell transplantation. Clinicians should be aware of this during health workup and postdonation follow-up of unrelated PBSC donors. Any abnormal and/or equivocal laboratory data, especially during the donor workup stage, should not be overlooked.
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- 2019
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30. Unrelated Donor Transplant Recipients Given Thymoglobuline Have Superior GRFS When Compared to Matched Related Donor Recipients Undergoing Transplantation without ATG.
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Othman, Jad, Greenwood, Matthew, Moore, John, Larsen, Stephen, Watson, Anne-Marie, Arthur, Chris, Bhattacharyya, Abir, Bilmon, Ian, Blyth, Emily, Bryant, Adam, Bryant, Christian, Dunlop, Lindsay, Fay, Keith, Gibson, John, Hamad, Nada, Kerridge, Ian, Kwan, John, Ma, David, Micklethwaite, Kenneth, and Milliken, Samuel
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- *
HEMATOPOIETIC stem cell transplantation , *STEM cell transplantation , *TRANSPLANTATION of organs, tissues, etc. , *CONDITIONED response , *GRAFT versus host disease , *ALEMTUZUMAB - Abstract
• A standardized protocol was implemented for peripheral blood stem cell allogeneic transplants for myeloid malignancies. • Unrelated and mismatched donor recipients were given Thymoglobuline while matched related donors did not receive Thymoglobuline. • Recipients from unrelated and mismatched donors had less chronic graft-versus-host disease (GVHD) requiring systemic therapy. • As a result, unrelated and mismatched donor transplants had superior GVHD-free, relapse-free survival. Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated donors (URDs) and mismatched related donors (MMRDs) typically have a higher incidence of acute and chronic graft-versus-host disease (GVHD) compared with matched related donors (MRDs). Anti-T-cell globulins (ATGs) are often used to reduce GVHD in these recipients. We report the outcomes of 211 adult peripheral blood stem cell transplant recipients with myeloid malignancies who received a standardized transplant protocol, in which ATG (Thymoglobuline 4.5 mg/kg) was administered to recipients of URD and MMRD (n = 147) but not MRD (n = 64) transplant. For all patients, incidence of acute GVHD grades 2 to 4 was 21.4%, and chronic GVHD was 35.0%. Two-year overall survival was 63.2% (95% confidence interval, 55.8% to 71.5%), relapse-free survival was 55.3% (47.4% to 64.6%), and GVHD-free, relapse-free survival (GRFS) was 30.7% (23.2% to 40.8%). There were no differences between recipients of MRDs and other donors in relapse, nonrelapse mortality, and overall and relapse-free survival. However, compared with MRD, recipients from URDs and MMRDs had reduced moderate to severe chronic GVHD (10.4% versus 30.1%, P =.002), less chronic GVHD requiring systemic therapy (19.4% versus 38.9%, P =. 006), and superior 2-year GRFS (35.5% versus 20.0%, P =. 003). In this retrospective review of nonrandomized transplant groups, outcomes of HSCT performed using an URD with ATG during conditioning were superior to transplant from an MRD without ATG. The addition of Thymoglobuline to conditioning in HSCT from MRD should be further examined in prospective trials. Image, graphical abstract [ABSTRACT FROM AUTHOR]
- Published
- 2020
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31. Severe Acute Respiratory Syndrome Coronavirus-2 Pandemia: Facts and Perspectives in a Bone Marrow Transplant Unit.
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Malagola, Michele, Polverelli, Nicola, Gandolfi, Lisa, Zollner, Tatiana, Bernardi, Simona, Zanaglio, Camilla, Re, Federica, Morello, Enrico, Turra, Alessandro, Isidori, Alessandro, and Russo, Domenico
- Subjects
BONE marrow ,COVID-19 ,TRANSPLANTATION of organs, tissues, etc. ,BONE marrow transplantation - Published
- 2020
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32. Current status of hematopoietic stem cell transplantation in the treatment of aplastic anemia.
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Wei Yuanfeng and Huang Dongping
- Subjects
- *
HEMATOPOIETIC stem cell transplantation , *CORD blood transplantation , *APLASTIC anemia , *STEM cell treatment , *ANEMIA treatment - Abstract
BACKGROUND: A great progress has been achieved in the allogeneic hematopoietic stem cell transplantation for aplastic anemia. However, graft-versus-host disease and graft failure after transplantation are still the main causes of non-relapse death, which seriously affect the survival of patients. OBJECTIVE: To summarize the current status and progress of allogeneic hematopoietic cell transplantation in the treatment of aplastic anemia. METHODS: The first author retrieved PubMed, CNKI, WanFang and VIP databases for the articles concerning allogeneic hematopoietic stem cell transplantation for aplastic anemia published from January 1990 to September 2019. The keywords were "aplastic anemia, matched sibling donor hematopoietic stem cell transplantation, unrelated donor hematopoietic stem cell transplantation, haploidentical hematopoietic stem cell transplantation, cord blood transplantation" in Chinese and English, respectively. Finally 55 eligible articles were included for result analysis. RESULTS AND CONCLUSION: HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation is the first choice. Unrelated donor hematopoietic stem cell transplantation may be an effective and feasible first-line therapy in pediatric severe aplastic anemia patients with no matched sibling donors. Haploidentical hematopoietic stem cell transplantation and cord blood transplantation can also be important transplantation methods for severe aplastic anemia when lack of HLA-matched donors. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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33. Collection of Peripheral Blood Progenitor Cells in 1 Day Is Associated with Decreased Donor Toxicity Compared to 2 Days in Unrelated Donors.
- Author
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Hsu, Jack W., Shaw, Bronwen E., Kim, Soyoung, Logan, Brent R., Sees, Jennifer A., Confer, Dennis L., Pulsipher, Michael A., Shah, Nirali, Switzer, Galen E., Abidi, Muneer H., Ahmed, Ibrahim A., Anderlini, Paulo N., Bredeson, Christopher, Chhabra, Saurabh, Dandoy, Christopher E., Diaz, Miguel Angel, Farhadfar, Nosha, Ganguly, Siddhartha, Gergis, Usama, and Hale, Gregory A.
- Subjects
- *
LEUKAPHERESIS , *BLOOD collection , *PROGENITOR cells , *BLOOD cells , *HEMATOPOIESIS , *BONE marrow cells , *BODY mass index - Abstract
• Donors who undergo collection in 1 day have less apheresis-related toxicity and fewer hospitalizations compared with donors with collection over 2 days. • In donors with collection over 2 days, the apheresis yield of mononuclear cells was greater on the second day compared with the first day. • Although there are statistically significant differences in the incidence of modified toxicity criteria and skeletal pain during apheresis, these differences might not be clinically significant. 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 <.001), younger (age <30 years, 48% versus 36%; P <.001), and have a higher body weight (83.0 kg versus 75.9 kg; P <.001) and body mass index (BMI; >30, 30% versus 22%; P <.001). Successful collection of the requested CD34+ cell count was achieved on the first day in 82% of 1-day collections and in 16% of 2-day collections. Despite not administering filgrastim the evening after the first day of collection in patients who underwent 2 days of apheresis, the median concentration of CD34+ cells/L in the product was higher on the second day of apheresis compared with the first day (23.8 × 106 CD34+/L on day 1 versus 28.7 × 106 CD34+/L on day 2; P <.001). Donors who underwent collection in 1 day were less likely to experience citrate toxicity (36% versus 52%; P <.001), hospitalization (1% versus 6%; P <.001), and other side effects related to apheresis (Modified Toxicity Criteria incidence: 20% versus 26%; P <.001). Female sex, older age, collection via central lines, and higher BMI were factors associated with greater likelihood for the development of toxicity, whereas less toxicity was noted in those with higher CD34+ counts and more blood processed on the first day of collection. We conclude that although unrelated donors can be successfully collected in 1 day or 2 days, 1-day apheresis procedures were associated with less overall toxicity, and thus we recommend single-day collections, especially if the requested number of cells have been collected in 1 day. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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34. Clinical significance of autologous blood transfusions in bone marrow harvest from unrelated donors.
- Author
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Fujiwara, Shin-ichiro, Ikeda, Kazuhiko, Kino, Shuichi, Tanaka, Asashi, Hasegawa, Yuichi, Fujino, Keizo, Makino, Shigeyoshi, Matsumoto, Mayumi, Yokohama, Akihiko, Takeshita, Akihiro, and Muroi, Kazuo
- Subjects
AUTOTRANSFUSION of blood ,HEMOGLOBINS ,BONE marrow transplantation ,RETROSPECTIVE studies ,IMPACT of Event Scale ,BONE marrow ,ORGAN donation ,PROBABILITY theory - Abstract
In the Japan Marrow Donor Program (JMDP), autologous blood is collected from most unrelated bone marrow (BM) donors. We retrospectively evaluated 5772 donors who underwent BM harvest between 2010 and 2015 through the JMDP. Autologous blood was collected in 96.8% of the donors; the wastage rate was 0.6%. Allogeneic blood transfusion was not required. The mean hemoglobin (Hb) levels were 12.1 g/dL after the BM harvest (mean 891 mL) together with autologous blood transfusion (mean 596 mL). Propensity-score matching was used to adjust the backgrounds. Among donors with harvested BM of 100-400 mL, autologous blood transfusion had no impact on Hb levels or complications after BM harvest. Among donors with harvested BM of > 400 mL, more autologous blood transfusion followed by a bleeding volume of ≤ 100 mL did not confer clinical benefit to donors compared with less autologous blood transfusion followed by a bleeding volume of > 300 mL. The findings of the present study suggest that autologous blood transfusion to BM donors is excessive in terms of Hb changes and post-harvest outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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35. Partially CD3+-Depleted Unrelated and Haploidentical Donor Peripheral Stem Cell Transplantation Has Favorable Graft-versus-Host Disease and Survival Rates in Pediatric Hematologic Malignancy.
- Author
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Seif, Alix E., Li, Yimei, Monos, Dimitri S., Heidemann, Stephanie C., Aplenc, Richard, Barrett, David M., Casper, James T., Freedman, Jason L., Grupp, Stephan A., Margolis, David A., Olson, Timothy S., Teachey, David T., Keever-Taylor, Carolyn A., Wang, Yongping, Talano, Julie-An M., and Bunin, Nancy J.
- Subjects
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STEM cell transplantation , *STEM cell donors , *PROGNOSIS , *GRAFT versus host disease , *HEMATOLOGIC malignancies , *LEUKAPHERESIS , *RITUXIMAB , *ALEMTUZUMAB - Abstract
• The study cohort comprised children with leukemia who underwent partially CD3+-depleted peripheral stem cell transplantation (PSCT). • Three-year overall survival was 61.8% (95% confidence interval [CI], 50.2% to 71.4%) and event-free survival was 52.0% (95% CI, 40.3% to 62.4%). • Age ≥15 years and second complete remission were associated with worse outcomes. • The incidence of severe chronic graft-versus-host disease was lower in CD3+-depleted PSCTthan in T cell-replete PSCT. Most children who may benefit from stem cell transplantation lack a matched related donor. Alternative donor transplantations with an unrelated donor (URD) or a partially matched related donor (PMRD) carry an increased risk of graft-versus-host-disease (GVHD) and mortality compared with matched related donor transplantations. We hypothesized that a strategy of partial CD3+/CD19+ depletion for URD or PMRD peripheral stem cell transplantation (PSCT) would attenuate the risks of GVHD and mortality. We enrolled 84 pediatric patients with hematologic malignancies at the Children's Hospital of Philadelphia and the Children's Hospital of Wisconsin between April 2005 and February 2015. Two patients (2.4%) experienced primary graft failure. Relapse occurred in 23 patients (27.4%; cumulative incidence 26.3%), and 17 patients (20.2%) experienced nonrelapse mortality (NRM). Grade III-IV acute GVHD was observed in 18 patients (21.4%), and chronic GVHD was observed and graded as limited in 24 patients (35.3%) and extensive in 8 (11.7%). Three-year overall survival (OS) was 61.8% (95% confidence interval [CI], 50.2% to 71.4%) and event-free survival (EFS) was 52.0% (95% CI, 40.3% to 62.4%). Age ≥15 years was associated with decreased OS (P =.05) and EFS (P =.05). Relapse was more common in children in second complete remission (P =.03). Partially CD3+-depleted alternative donor PSCT NRM, OS, and EFS compare favorably with previously published studies of T cell-replete PSCT. Historically, T cell-replete PSCT has been associated with a higher incidence of extensive chronic GVHD compared with limited chronic GVHD, which may explain the comparatively low relapse and NRM rates in our study cohort despite similar overall rates of chronic GVHD. Partial T cell depletion may expand donor options for children with malignant transplantation indications lacking a matched related donor by mitigating, but not eliminating, chronic GVHD. [ABSTRACT FROM AUTHOR]
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- 2020
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36. Role of Race/Ethnicity in Donor Decisions about Unrelated Hematopoietic Progenitor Cell Donation: Exploring Reasons for Higher Attrition among Racial/Ethnic Minorities.
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Anthias, Chloe, Shaw, Bronwen E., Bruce, Jessica G., Confer, Dennis L., Abress, Linda K., Dew, Mary Amanda, Billen, Annelies, O'Leary, Ann, Braund, Henny, and Switzer, Galen E.
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MINORITIES , *RACE , *PROGENITOR cells , *ETHNICITY , *ETHNIC groups , *HEMAPHERESIS - Abstract
• Potential HPC donors who opted out were more ambivalent and had more concerns. • Potential HPC donors who opted out reported less interaction with the registry. • Sixteen percent said more interaction with the registry would have changed their decision. • Minorities reported more religious objections and mistrust about HPC allocation. • Patterns of results were similar for UK- and US-based registries. There are more than 30 million potential unrelated hematopoietic progenitor cell (HPC) donors listed on international registries, but 30% to 50% are unavailable after matching a patient. In the United States racial/ethnic minorities opt out of donation at higher rates, and a previous study identified factors associated both with attrition and ethnic group membership. Attrition among minorities is also higher in the Anthony Nolan UK registry (35% in white British [WB] and 56% in nonwhite British [NWB]), but it is not clear what factors produce higher attrition in the United Kingdom and whether they are similar to those found in the United States. Three hundred fifty-seven UK potential donors who matched a patient completed a questionnaire. Key factors were compared by donation decision (continue or opt out) and by race/ethnicity (WB versus NWB). The pattern of UK results was compared with that of the previous US study for variables assessed in both studies. Across WB and NWB donors, higher attrition was associated with poorer physical/mental health, greater ambivalence, and more concerns about donation. Donors who opted out also reported less interaction with the registry, and 16% indicated that more interaction with the registry would have changed their decision. Those opting out of the registry and minorities were both more likely to report religious objections to donation and to mistrust the fairness of HPC allocation. The pattern of findings was similar in UK and US samples. Registries should maintain contact with potential donors after recruitment, aiming to educate members about the donation procedure and to address potential misconceptions associated with religious beliefs and HPC allocation. [ABSTRACT FROM AUTHOR]
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- 2020
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37. Pre‐transplant short telomeres are associated with high mortality risk after unrelated donor haematopoietic cell transplant for severe aplastic anaemia.
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Wang, Youjin, McReynolds, Lisa J., Dagnall, Casey, Katki, Hormuzd A., Spellman, Stephen R., Wang, Tao, Hicks, Belynda, Freedman, Neal D., Jones, Kristine, Lee, Stephanie J., Savage, Sharon A., and Gadalla, Shahinaz M.
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TELOMERES , *ANEMIA , *CELL transplantation , *POLYMERASE chain reaction , *TRANSPLANTATION of organs, tissues, etc. , *SPEECH apraxia - Abstract
Summary: Telomeres are essential for chromosomal stability and markers of biological age. We evaluated the effect of pre‐transplant short (<10th percentile‐for‐age) or very short (<5th or <1st percentile‐for‐age) leucocyte telomere length on survival after unrelated donor haematopoietic cell transplantation (HCT) for acquired severe aplastic anaemia (SAA). Patient pre‐transplant blood samples and clinical data were available at the Center for International Blood and Marrow Transplant Research. We used quantitative real time polymerase chain reaction to measure relative telomere length (RTL) in 490 SAA patients who received HCT between 1990 and 2013 (median age = 20 years). One hundred and twelve patients (22·86%) had pre‐HCT RTL <10th percentile‐for‐age, with the majority below the 5th percentile (N = 80, 71·43%). RTL <10th percentile‐for‐age was associated with a higher risk of post‐HCT mortality (hazard ratio [HR] = 1·78, 95% confidence interval [CI]=1·18–2·69, P = 0·006) compared with RTL ≥50th percentile; no survival differences were noted in longer RTL categories (P > 0·10). Time‐dependent effects for post‐HCT mortality were only observed in relation to very short RTL; HR comparing RTL <5th versus ≥5th percentile = 1·38, P = 0·15 for the first 12 months after HCT, and HR = 3·91, P < 0·0001, thereafter, P‐heterogeneity = 0·008; the corresponding HRs for RTL <1st versus ≥1st percentile = 1·29, P = 0·41, and HR = 5·18, P < 0·0001, P‐heterogeneity = 0·005. The study suggests a potential role for telomere length in risk stratification of SAA patients in regard to their HCT survival. [ABSTRACT FROM AUTHOR]
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- 2020
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38. Comparable Long-Term Outcome after Allogeneic Stem Cell Transplantation from Sibling and Matched Unrelated Donors in Patients with Acute Myeloid Leukemia Older Than 50 Years: A Report on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
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Shimoni, Avichai, Labopin, Myriam, Savani, Bipin, Byrne, Michael, Volin, Liisa, Finke, Jürgen, Niederwieser, Dietger, Ehninger, Gerhard, Blaise, Didier, Beelen, Dietrich, Tabrizi, Reza, Sengeloev, Henrik, Ganser, Arnold, Cornelissen, Jan J., Mohty, Mohamad, and Nagler, Arnon
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STEM cell transplantation , *ACUTE myeloid leukemia , *ACUTE leukemia , *SIBLINGS , *BONE marrow , *ALEMTUZUMAB - Abstract
• Marked improvement has been achieved in recent years in stem cell transplantation (SCT) from unrelated donors. • Long-term outcome is equivalent after SCT from unrelated and sibling donors. • Patients who are leukemia-free 2 years after SCT can expect a favorable outcome. Allogeneic stem cell transplantation (SCT) is potentially curative therapy in acute myeloid leukemia (AML). Marked improvement has been achieved with SCT from matched unrelated donors (MUDs) in recent years. However, there are limited data comparing the long-term outcomes (beyond 10 years) after SCT from sibling donors and MUDs in older patients with AML. We analyzed these outcomes in a large cohort of patients with AML (n = 1134), age ≥50 years, who were alive and leukemia-free 2 years after SCT from matched siblings (n = 848) or MUDs (n = 286), with a median follow-up of 8.9 years. The median age was 56 and 58 years after SCT from siblings and MUDs, respectively (P =.005). In the sibling group, 77%, 12%, and 11% were in first complete remission (CR1), second complete remission (CR2), and active leukemia at SCT compared with 50%, 25%, and 25% in the MUD group, respectively (P <.001). Sixty-one percent of siblings and 62% of MUDs had reduced-intensity conditioning (P =.78). The 10-year leukemia-free survival (LFS) of patients surviving leukemia-free 2 years after SCT was 72% and 62%, respectively (P =.30). Multivariate analysis identified active leukemia at SCT (hazard ratio [HR], 1.86; P =.0001) or CR2 (HR, 1.51; P =.02) compared with CR1, female recipients (HR, 0.71; P =.006), adverse cytogenetics (HR, 2.52; P =.01), and prior graft-versus-host disease (HR, 1.31; P =.04) as independent factors predicting LFS. Donor and conditioning type were not significant. The cumulative incidence was 15% and 17% (P =.97) for late relapse mortality and 13% and 21% for late nonrelapse mortality, respectively (P =.15). In conclusion, long-term LFS is similar, and patients who are leukemia-free 2 years after SCT can expect favorable outcomes with both donor types. [ABSTRACT FROM AUTHOR]
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- 2019
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39. Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT
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Eolia Brissot, Myriam Labopin, Matthias Stelljes, Gerhard Ehninger, Rainer Schwerdtfeger, Jürgen Finke, Hans-Jochem Kolb, Arnold Ganser, Kerstin Schäfer-Eckart, Axel R. Zander, Donald Bunjes, Stephan Mielke, Wolfgang A. Bethge, Noël Milpied, Peter Kalhs, Igor-Woflgang Blau, Nicolaus Kröger, Antonin Vitek, Martin Gramatzki, Ernst Holler, Christoph Schmid, Jordi Esteve, Mohamad Mohty, and Arnon Nagler
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Acute myeloid leukemia ,Refractory ,Allogeneic stem cell transplantation ,HLA-matched related donor ,Unrelated donor ,Graft-versus-host disease ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML. Methods The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results HSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS). Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality. Conclusions HSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients’ outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an unrelated donor is a suitable option, and therefore, initiation of an early search for allocating a suitable donor is indicated.
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- 2017
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40. Graft-versus-Host Disease Prophylaxis with Post- Transplantation Cyclophosphamide in Chronic Myeloid Leukemia Patients Undergoing Allogeneic Hematopoietic Cell Transplantation from an Unrelated or Mismatched Related Donor: A Comparative Study from the Chronic Malignancies Working Party of the EBMT (CMWP-EBMT).
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Ortí G, Gras L, Koster L, Kulagin A, Byrne J, Apperley JF, Halaburda K, Blau IW, Clark A, Kröger N, Griskevicius L, Carlson K, Collin M, Bloor A, Raiola AM, Blaise D, Aljurf M, López-Corral L, Sakellari I, Beguin Y, Wrobel T, de Rosa L, de Lavallade H, Hayden PJ, McLornan D, Chalandon Y, and Yakoub-Agha I
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- Adult, Humans, Chronic Disease, Cyclophosphamide therapeutic use, Retrospective Studies, Unrelated Donors, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Leukemia, Myeloid
- Abstract
Outcomes following allogeneic hematopoietic cell transplantation (allo-HCT) for chronic myeloid leukemia (CML) with post-transplantation cyclophosphamide (PTCy) using an unrelated donor (UD) or a mismatched related donor (MMRD) remain unknown. We report a retrospective comparison of PTCy-based allo-HCT from a UD, non-PTCy allo-HCT from a UD, and PTCy allo-HCT from an MMRD. Inclusion criteria were adult patients with CML undergoing first allo-HCT between 2012 and 2019 from a UD with either PTCy or non-PTCy graft-versus-host disease (GVHD) prophylaxis or from an MMRD using PTCy. The primary endpoint was GVHD-free/relapse-free survival (GRFS). A total of 1341 patients were included (82% in the non-PTCy UD cohort). With a median follow-up of 34.9 months, the 3-year GRFS was 43% in the non-PTCy cohort, 37% in the PTCy-UD cohort, and 39% PTCy-MMRD cohort (P = .15). Multivariable analyses revealed no significant differences among the 3 cohorts in terms of overall survival (OS), progression-free survival, RI, and nonrelapse mortality. Factors independently associated with worse OS in the overall cohort were Karnofsky Performance Status <90 (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.41 to 2.45; P < .001), older age (HR, 1.24, 95% CI, 1.11 to 1.38; P < .001), and disease stage (compared to chronic phase [CP] 1): blast phase (HR, 2.25; 95% CI, 1.60 to 3.16; P < .001), accelerated phase (HR, 1.63; 95% CI, 1.05 to 2.54; P = .03), and CP >2 (HR, 1.58; 95% CI, 1.15 to 2.17; P = .005). These results suggest that allo-HCT in patients with CML using either a UD or an MMRD with PTCy-based GVHD prophylaxis are feasible transplantation, platforms and that the disease stage at allo-HCT remains a major prognostic factor, highlighting the importance of closely monitoring CML patients and proposing transplantation when indicated when still in CP1., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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41. The History of Pediatric Hematopoietic Cell Transplantation Around the World
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Sanders, Jean E., Coccia, Peter F., Niethammer, Dietrich, Bonfim, Carmemm M., Shaw, Peter J., Li, Chi-Kong, Smith, Franklin O., editor, Reaman, Gregory H., editor, and Racadio, Judy M., editor
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- 2014
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42. HLA Matching in Unrelated Stem Cell Transplantation up to Date.
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Fürst, Daniel, Neuchel, Christine, Tsamadou, Chrysanthi, Schrezenmeier, Hubert, and Mytilineos, Joannis
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STEM cell transplantation , *HEMATOPOIETIC stem cell transplantation , *BONE marrow transplantation , *THERAPEUTICS , *LEWIS basicity - Abstract
Unrelated hematopoietic stem cell transplantation (HSCT) has evolved from an experimental protocol to a potentially curative first-line treatment in certain disease instances. Factors enabling this transformation were the optimization of treatment protocols and supportive care as well as the availability of a large number of donors worldwide along with the higher quality and reliability of HLA typing. The main criterion for donor selection is HLA compatibility. In this review we discuss the current clinical evidence of HLA matching in unrelated HSCT. In this context, we address methodical aspects of transplantation immunobiology research and discuss the impact of locus and resolution of HLA differences. Furthermore, we address special constellations such as unidirectional mismatches or the presence of nonexpressed alleles as well as HLA alloimmunization and describe the perspective for HLA typing and matching strategies in the future, given the implementation of novel complete or near-complete gene typing approaches using next-generation sequencing short read technology, which are now entering the standard of clinical care. [ABSTRACT FROM AUTHOR]
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- 2019
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43. Comparable Outcomes of First-Line Hematopoietic Stem Cell Transplantation from Unrelated and Matched Sibling Donors in Adult Patients with Aplastic Anemia: A Retrospective Single-Center Study.
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Zhang, Yuping, Wu, Liangliang, Mo, Wenjian, Zhou, Ming, Li, Yumiao, Chen, Xiaowei, Wang, Caixia, Pan, Shiyi, Xu, Shilin, Zhou, Wei, Zhou, Ruiqing, and Wang, Shunqing
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HEMATOPOIETIC stem cell transplantation , *APLASTIC anemia , *PROPENSITY score matching , *GRAFT versus host disease , *ALEMTUZUMAB , *SIBLINGS - Abstract
• We compared the outcomes of consecutive adult patients with (AA) undergoing first-line unrelated donor (URD) or matched sibling donor (MSD) hematopoietic stem cell transplantation (HSCT). • The data indicate that the outcomes of first-line URD HSCT in adults with AA were not inferior to those of MSD HSCT. To explore the feasibility of upfront unrelated donor (URD) hematopoietic stem cell transplantation (HSCT) in the treatment of adult aplastic anemia (AA), we conducted a retrospective, single-center study and compared the outcomes of adult patients who underwent first-line URD HSCT or matched sibling donor (MSD) HSCT between August 2012 and June 2018. In all, 23 URD HSCT recipients had an increased cumulative incidence of grade II acute graft-versus-host disease (aGVHD) (21.7% versus 3.4%; P =.007), but similar rates of secondary graft failure (8.7 ± 6.0% versus 6.9 ± 3.4%; P =.764), chronic GVHD (cGVHD) (18.2% versus 8.8%; P =.285), extensive cGVHD (9.1% versus 3.5%; P =.328), 5-year estimated overall survival (87.0% versus 94.2%; P =.501), and 5-year estimated failure-free survival (82.0% versus 89.3%; P =.404) compared with 58 MSD HSCT recipients treated during the same period. After using propensity score matching to reduce the influence of potential confounders, the 2 groups were well balanced in terms of pretransplantation clinical factors. The median survival time was similar, and no significant differences in the aforementioned outcomes were observed between the 2 groups. Our results suggest that URD HSCT may be an effective and feasible option for first-line therapy in adult AA patients who lack an MSD. [ABSTRACT FROM AUTHOR]
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- 2019
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44. Comparison of Outcomes of Allogeneic Transplantation for Primary Myelofibrosis among Hematopoietic Stem Cell Source Groups.
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Murata, Makoto, Takenaka, Katsuto, Uchida, Naoyuki, Ozawa, Yukiyasu, Ohashi, Kazuteru, Kim, Sung-Won, Ikegame, Kazuhiro, Kanda, Yoshinobu, Kobayashi, Hikaru, Ishikawa, Jun, Ago, Hiroatsu, Hirokawa, Makoto, Fukuda, Takahiro, Atsuta, Yoshiko, and Kondo, Takeshi
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HEMATOPOIETIC stem cell transplantation , *CORD blood , *MYELOFIBROSIS , *TRANSPLANTATION of organs, tissues, etc. , *HEMATOPOIETIC stem cells , *ALEMTUZUMAB - Abstract
• The use of umbilical cord blood grafts is associated with increased nonrelapse mortality. • Reduced-intensity conditioning does not necessarily decrease nonrelapse mortality. • Older age and transfusion dependency are associated with a lower survival rate. The choice of alternative donor is a major issue in allogeneic hematopoietic stem cell transplantation (HSCT) for patients with primary myelofibrosis (PMF) without an HLA-matched related donor. We conducted this retrospective study using the Japanese national registry data for 224 PMF patients to compare the outcomes of first allogeneic HSCT from HLA-matched related donor bone marrow (Rtd-BM), HLA-matched related donor peripheral blood stem cells (Rtd-PB), HLA-matched unrelated donor bone marrow (UR-BM), unrelated umbilical cord blood (UR-UCB), and other hematopoietic stem cell grafts. Nonrelapse mortality (NRM) rates at 1 year after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantations were 16%, 36%, 30%, 41%, and 48%, respectively. Multivariate analysis identified UR-UCB transplantation, other transplantation, frequent RBC transfusion before transplantation, and frequent platelet (PLT) transfusion before transplantation as predictive of higher NRM. Relapse rates at 1 year after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantation were 14%, 17%, 11%, 14%, and 15%, respectively. No specific factor was associated with the incidence of relapse. Overall survival (OS) at 1 and 4 years after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantation were 81% and 71%, 58% and 52%, 61% and 46%, 48% and 27%, and 48% and 41%, respectively. Multivariate analysis identified older patient age, frequent RBC transfusion before transplantation, and frequent PLT transfusion before transplantation as predictive of lower OS. In conclusion, UR-UCB transplantation, as well as UR-BM transplantation, can be selected for PMF patients without an HLA-identical related donor. However, careful management is required for patients after UR-UCB transplantation because of the high NRM. Further studies including more patients after HLA-haploidentical related donor and HLA-mismatched unrelated donor transplantation would provide more valuable information for patients with PMF when making decisions regarding the choice of alternative donor. [ABSTRACT FROM AUTHOR]
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- 2019
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45. The Concentration of Total Nucleated Cells in Harvested Bone Marrow for Transplantation Has Decreased over Time.
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Prokopishyn, Nicole L., Logan, Brent R., Kiefer, Deidre M., Sees, Jennifer A., Chitphakdithai, Pintip, Ahmed, Ibrahim A., Anderlini, Paolo N., Beitinjaneh, Amer M., Bredeson, Christopher, Cerny, Jan, Chhabra, Saurabh, Daly, Andrew, Diaz, Miguel Angel, Farhadfar, Nosha, Frangoul, Haydar A., Ganguly, Siddhartha, Gastineau, Dennis A., Gergis, Usama, Hale, Gregory A., and Hematti, Peiman
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BONE marrow transplantation , *BONE marrow cells , *CORD blood , *HEMATOPOIETIC stem cells , *BLOOD cells , *STEM cells - Abstract
Bone marrow (BM) is an essential source of hematopoietic stem cell grafts for many allogeneic hematopoietic cell transplant (HCT) recipients, including adult patients (for specific diseases and transplantation strategies) and the majority of pediatric recipient. However, since the advent of granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts, there has been a significant decrease in the use of BM in HCT, thought to be due mainly to the increased logistical challenges in harvesting BM compared with PBSCs, as well as generally no significant survival advantage of BM over PBSCs. The decreased frequency of collection has the potential to impact the quality of BM harvests. In this study, we examined >15,000 BM donations collected at National Marrow Donor Program centers between 1994 and 2016 and found a significant decline in the quality of BM products, as defined by the concentration of total nucleated cells (TNCs). The mean TNC concentration in BM donations dropped from 21.8 × 106 cells/mL in the earliest era (1994 to 1996) to 18.7 × 106 cells/mL in the most recent era (2012 to 2016) (means ratio,.83; P <.001). This decline in BM quality was seen despite the selection of more donors perceived to be optimal (eg, younger and male). Multivariate regression analysis showed that higher-volume centers (performing >30 collections per era) had better-quality harvests with higher concentrations of TNCs collected. In conclusion, we have identified a significant decrease in the quality of BM collections over time, and lower-volume collection centers had poorer-quality harvests. In this analysis, we could not elucidate the direct cause for this finding, suggesting the need for further studies to investigate the key factors responsible and to explore the impact on transplant recipients. [ABSTRACT FROM AUTHOR]
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- 2019
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46. Direct HLA Genetic Comparisons Identify Highly Matched Unrelated Donor-Recipient Pairs with Improved Transplantation Outcome.
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Vazirabad, Ibrahim, Chhabra, Saurabh, Nytes, James, Mehra, Vatsal, Narra, Ravi K., Szabo, Aniko, Jerkins, James H., Dhakal, Binod, Hari, Parameswaran, and Anderson, Matthew W.
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ALLELES , *CELL transplantation , *BUSULFAN , *TRANSPLANTATION of organs, tissues, etc. , *IMMUNE recognition , *GRAFT versus host disease , *GENETIC polymorphisms - Abstract
• Next-generation sequencing (NGS) of HLA loci can identify polymorphisms in both antigen recognition domain (ARD) and non-ARD encoding exons, introns, and untranslated regions. • NGS-based sequencing of eleven HLA loci in a retrospective cohort of 166 unrelated donor-recipient hematopoietic cell transplantation pairs demonstrated that those with no genetic mismatch had superior survival and acute graft-versus-host disease outcomes, thereby supporting the adoption of NGS for unrelated donor selection. HLA matching by allele-level genotyping is largely based on genetic similarity between a few exons that encode the antigen recognition domain (ARD) of the HLA protein. Next-generation sequencing (NGS) can identify HLA genetic polymorphisms in non-ARD-encoding exons, introns, and untranslated regions, but the impact of these polymorphisms on hematopoietic cell transplantation (HCT) outcome is unclear. We performed NGS-based sequencing of 11 HLA loci on a well-characterized retrospective cohort of 166 unrelated donor-recipient HCT pairs. Genetic differences between HCT pairs were identified and visualized using a novel bioinformatics approach that directly compares phased full-length HLA sequences. Our approach was able to correctly classify HCT pairs without known HLA allele-level mismatches and also to identify a subset of HLA allele-matched HCT pairs with very few to no genetic differences in the sequenced HLA regions. This highly HLA genetically matched unrelated HCT group shows improved overall survival and reduced acute graft-versus-host disease compared with HCT pairs with HLA allele-level mismatches. These results suggest that direct genetic matching of HLA loci may offer an additional means of HCT donor selection beyond traditional HLA allele comparisons and suggests that genetic similarity as defined by HLA sequencing may have a novel role in unrelated HCT donor selection. Finally, our approach can enable larger cohort studies with adequate power to detect differences in other HCT outcomes based on genetic similarity within the HLA loci. [ABSTRACT FROM AUTHOR]
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- 2019
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47. Risk factors affecting outcome of unrelated cord blood transplantation for children with familial haemophagocytic lymphohistiocytosis.
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Furtado‐Silva, Juliana Montibeller, Paviglianiti, Annalisa, Ruggeri, Annalisa, Boelens, Jaap Jan, Veys, Paul, Ahmari, Ali Abdallah, Zecca, Marco, Locatelli, Franco, Michel, Gerard, Volt, Fernanda, Kenzey, Chantal, Sedlacek, Petr, Rao, Kanchan, Lankester, Arjan, Gluckman, Eliane, and Rocha, Vanderson
- Abstract
Summary: Allogeneic haematopoietic stem cell transplantation is still the only available curative option for Familial Haemophagocytic Lymphohistiocytosis (FHLH). Most studies report outcomes after bone marrow or peripheral blood stem cell transplantation. We analysed the outcomes of 118 children with FHLH undergoing single‐unit umbilical cord blood transplantation performed from 1996 to 2014. Myeloablative conditioning regimen was given to 90% of the patients, and was mostly busulfan‐based (n = 81, 76%), including anti‐thymocyte globulin or alemtuzumab (n = 102, 86%). The cumulative incidence of Day 60 neutrophil engraftment was 85%; and that of non‐relapse mortality and acute graft‐versus‐host disease (GvHD) was 21% and 33% at 100 days, respectively. The 6‐year cumulative incidence of chronic GvHD was 17% and the 6‐year probability of overall survival was 55%. In multivariate analysis, children receiving a graft with a total nucleated cell dose greater than 9·9 × 107/kg had a better overall survival (hazard ratio [HR]: 0·49, 95% CI: 0·27–0·88, P = 0·02). Degree of human leucocyte antigen (HLA) matching was associated with improved disease‐free survival (5/6 vs. 6/6 HR: 2·11, 95% confidence interval [CI]: 1·01–4·4, P = 0·05 and ≤4/6 vs. 6/6, HR: 2·82, CI: 1·27–6·23, P = 0·01). Umbilical cord blood transplantation with a high cell dose and good HLA match is a suitable alternative option to haematopoietic stem cell transplantation in children with FHLH who lack a HLA‐matched donor. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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48. Allocation to Matched Related or Unrelated Donor Results in Similar Clinical Outcomes without Increased Risk of Failure to Proceed to Transplant among Patients with Acute Myeloid Leukemia: A Retrospective Analysis from the Time of Transplant Approval.
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Rodríguez-Arbolí, Eduardo, Márquez-Malaver, Francisco José, Rodríguez-Torres, Nancy, Caballero-Velázquez, Teresa, Escamilla-Gómez, Virginia, Calderón-Cabrera, Cristina, Falantes-González, José Francisco, Solé-Rodríguez, María, García-Ramírez, Patricia, Moya-Arnao, María, Carreras, Enric, Espigado-Tocino, Ildefonso, and Pérez-Simón, José Antonio
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ACUTE myeloid leukemia , *HEMATOPOIETIC stem cell transplantation , *GRAFT versus host disease , *MYELOID leukemia , *DISEASE progression - Abstract
Highlights • Waiting time to allogeneic hematopoietic stem cell transplantation was longer in acute myelogenous leukemia patients allocated to an unrelated donor when compared with patients assigned to a matched related donor. • Despite the delay associated to unrelated donor allocation, a similar proportion of patients failed to reach allogeneic hematopoietic stem cell transplantation in both groups. • Transplantation outcomes were comparable among donor allocation groups. • No significant differences in clinical outcomes from the time of transplant approval were observed. Abstract Clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo-SCT) from unrelated donors (URDs) approach those of matched related donor (MRD) transplants in patients with acute myeloid leukemia (AML). Yet, available data fail to account for differences in pretransplantation outcomes between these donor selection strategies. In this regard, URD allo-HSCT is associated with longer waiting times to transplantation, potentially resulting in higher probabilities of failure to reach transplant. We retrospectively analyzed 108 AML patients accepted for first allo-HSCT from the time of approval to proceed to transplant. Fifty-eight (54%) patients were initially allocated to MRD, while URD search was initiated in 50 (46%) patients. Time to transplant was longer in patients allocated to a URD when compared with patients assigned to an MRD (median 142 days versus 100 days; p <.001). Forty-three of 58 (74%) patients in the MRD group and 35 of 50 (70%) patients in the URD group underwent transplantation (odds ratio [OR], 1.22; p =.63). Advanced disease status at the time of allo-HSCT approval was the only predictor of failure to reach transplantation in the multivariate analysis (OR, 4.78; p =.001). Disease progression was the most common cause of failure to reach allo-HSCT (66.7%) in both the MRD and URD groups. With a median follow-up from transplantation of 14.5 (interquartile range, 5 to 29) months, the 2-year estimate of overall survival (OS) from allo-HSCT was 46% in the MRD group and 57% in the URD group (p =.54). There were no differences in OS according to donor type allocation in the multivariate analysis (hazard ratio, 1.01; p =.83). When including patients from the time of transplant approval, 2-year OS was 39% in the MRD group versus 42% in the URD group. Our study suggests that allocation of AML patients to URDs may result in comparable clinical outcomes to MRD assignment without a significant increase in the risk of failure to reach transplant. [ABSTRACT FROM AUTHOR]
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- 2019
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49. Unrelated donor versus matched sibling donor in adults with acute myeloid leukemia in first relapse: an ALWP-EBMT study
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Annalisa Ruggeri, Giorgia Battipaglia, Myriam Labopin, Gerhard Ehninger, Dietrich Beelen, Johanna Tischer, Arnold Ganser, Rainer Schwerdtfeger, Bertram Glass, Jurgen Finke, Mauricette Michallet, Matthias Stelljes, Pavel Jindra, Renate Arnold, Nicolaus Kröger, Mohamad Mohty, and Arnon Nagler
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Acute myeloid leukemia ,Relapse ,Matched sibling donor ,Unrelated donor ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Allogeneic stem cell transplantation is the only curative option for patients with acute myeloid leukemia (AML) experiencing relapse. Either matched sibling donor (MSD) or unrelated donor (UD) is indicated. Methods We analyzed 1554 adults with AML transplanted from MSD (n = 961) or UD (n = 593, HLA-matched 10/10, n = 481; 9/10, n = 112). Compared to MSD, UD recipients were older (49 vs 52 years, p = 0.001), transplanted more recently (2009 vs 2006, p = 0.001), and with a longer interval to transplant (10 vs 9 months, p = 0.001). Conditioning regimen was more frequently myeloablative for patients transplanted with a MSD (61 vs 46 %, p = 0.001). Median follow-up was 28 (range 3–157) months. Results Cumulative incidence (CI) of neutrophil engraftment (p = 0.07), grades II–IV acute GVHD (p = 0.11), chronic GVHD (p = 0.9), and non-relapse mortality (NRM, p = 0.24) was not different according to the type of donor. At 2 years, CI of relapse (relapse incidence (RI)) was 57 vs 49 % (p = 0.001). Leukemia-free survival (LFS) at 2 years was 21 vs 26 % (p = 0.001), and overall survival (OS) was 26 vs 33 % (p = 0.004) for MSD vs UD, respectively. Chronic GVHD as time-dependent variable was associated with lower RI (HR 0.78, p = 0.05), higher NRM (HR 1.71, p = 0.001), and higher OS (HR 0.69, p = 0.001). According to HLA match, RI was 57 vs 50 vs 45 %, (p = 0.001) NRM was 23 vs 23 vs 29 % (p = 0.26), and LFS at 2 years was 21 vs 27 vs 25 % (p = 0.003) for MSD, 10/10, and 9/10 UD, respectively. In multivariate analysis adjusted for differences between the two groups, UD was associated with lower RI (HR 0.76, p = 0.001) and higher LFS (HR 0.83, p = 0.001) compared to MSD. Interval between diagnosis and transplant was the other factor associated with better outcomes (RI (HR 0.62, p
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- 2016
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50. The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
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Marie T. Rubio, Bipin N. Savani, Myriam Labopin, Emmanuelle Polge, Dietger Niederwieser, Arnold Ganser, Rainer Schwerdtfeger, Gerhard Ehninger, Jürgen Finke, Arnold Renate, Charles Craddock, Nicolaus Kröger, Michael Hallek, Pavel Jindra, Mohamad Mohty, and Arnon Nagler
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Allogeneic stem cell transplantation ,Unrelated donor ,Older patients ,HLA matching ,Acute leukemia ,Toxicity ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited. Methods We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. Results HLA matching had no impact on engraftment (p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II–IV acute graft-versus-host disease (GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD. Conclusions Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies.
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- 2016
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