7 results on '"Nakamura, Ryotaro"'
Search Results
2. Comparing transplant outcomes in ALL patients after haploidentical with PTCy or matched unrelated donor transplantation
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Al Malki, Monzr M, Yang, Dongyun, Labopin, Myriam, Afanasyev, Boris, Angelucci, Emanuele, Bashey, Asad, Socié, Gérard, Karduss-Urueta, Amado, Helbig, Grzegorz, Bornhauser, Martin, Niittyvuopio, Riitta, Ganser, Arnold, Ciceri, Fabio, Brecht, Arne, Koc, Yener, Bejanyan, Nelli, Ferraro, Francesca, Kebriaei, Partow, Mokhtari, Sally, Ghobadi, Armin, Nakamura, Ryotaro, Forman, Stephen J, Champlin, Richard, Mohty, Mohamad, Ciurea, Stefan O, and Nagler, Arnon
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Transplantation ,Hematology ,Stem Cell Research ,Clinical Research ,Stem Cell Research - Nonembryonic - Human ,Rare Diseases ,Pediatric Research Initiative ,Good Health and Well Being ,Adult ,Cyclophosphamide ,Humans ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Retrospective Studies ,Transplantation Conditioning ,Unrelated Donors ,Cardiovascular medicine and haematology - Abstract
We compared outcomes of 1461 adult patients with acute lymphoblastic leukemia (ALL) receiving hematopoietic cell transplantation (HCT) from a haploidentical (n = 487) or matched unrelated donor (MUD; n = 974) between January 2005 and June 2018. Graft-versus-host disease (GVHD) prophylaxis was posttransplant cyclophosphamide (PTCy), calcineurin inhibitor (CNI), and mycophenolate mofetil (MMF) for haploidentical, and CNI with MMF or methotrexate with/without antithymoglobulin for MUDs. Haploidentical recipients were matched (1:2 ratio) with MUD controls for sex, conditioning intensity, disease stage, Philadelphia-chromosome status, and cytogenetic risk. In the myeloablative setting, day +28 neutrophil recovery was similar between haploidentical (87%) and MUD (88%) (P = .11). Corresponding rates after reduced-intensity conditioning (RIC) were 84% and 88% (P = .47). The 3-month incidence of grade II-IV acute GVHD (aGVHD) and 3-year chronic GVHD (cGVHD) was similar after haploidentical compared with MUD: myeloablative conditioning, 33% vs 34% (P = .46) for aGVHD and 29% vs 31% for cGVHD (P = .58); RIC, 31% vs 30% (P = .06) for aGVHD and 24% vs 29% for cGVHD (P = .86). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 44% and 51% with haploidentical and MUD (P = .56). Corresponding rates after RIC were 43% and 42% (P = .6). In this large multicenter case-matched retrospective analysis, despite the limitations of a registry-based study (ie, unavailability of key elements such as minimal residual disease testing), our analysis indicated that outcomes of patients with ALL undergoing HCT from a haploidentical donor were comparable with 8 of 8 MUD transplantations.
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- 2020
3. Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research
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Lazaryan, Aleksandr, Dolan, Michelle, Zhang, Mei-Jie, Wang, Hai-Lin, Kharfan-Dabaja, Mohamed A, Marks, David I, Bejanyan, Nelli, Copelan, Edward, Majhail, Navneet S, Waller, Edmund K, Chao, Nelson, Prestidge, Tim, Nishihori, Taiga, Kebriaei, Partow, Inamoto, Yoshihiro, Hamilton, Betty, Hashmi, Shahrukh K, Kamble, Rammurti T, Bacher, Ulrike, Hildebrandt, Gerhard C, Stiff, Patrick J, McGuirk, Joseph, Aldoss, Ibrahim, Beitinjaneh, Amer M, Muffly, Lori, Vij, Ravi, Olsson, Richard F, Byrne, Michael, Schultz, Kirk R, Aljurf, Mahmoud, Seftel, Matthew, Savoie, Mary Lynn, Savani, Bipin N, Verdonck, Leo F, Cairo, Mitchell S, Hossain, Nasheed, Bhatt, Vijaya Raj, Frangoul, Haydar A, Abdel-Azim, Hisham, Malki, Monzr Al, Munker, Reinhold, Rizzieri, David, Khera, Nandita, Nakamura, Ryotaro, Ringdén, Olle, van der Poel, Marjolein, Murthy, Hemant S, Liu, Hongtao, Mori, Shahram, De Oliveira, Satiro, Bolaños-Meade, Javier, Elsawy, Mahmoud, Barba, Pere, Nathan, Sunita, George, Biju, Pawarode, Attaphol, Grunwald, Michael, Agrawal, Vaibhav, Wang, Youjin, Assal, Amer, Caro, Paul Castillo, Kuwatsuka, Yachiyo, Seo, Sachiko, Ustun, Celalettin, Politikos, Ioannis, Lazarus, Hillard M, Saber, Wael, Sandmaier, Brenda M, De Lima, Marcos, Litzow, Mark, Bachanova, Veronika, Weisdorf, Daniel, and Committee of the CIBMTR, Acute Leukemia
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Oncology and Carcinogenesis ,Rare Diseases ,Pediatric Cancer ,Transplantation ,Childhood Leukemia ,Hematology ,Cancer ,Pediatric ,Stem Cell Research ,Adult ,Chromosome Aberrations ,Hematopoietic Stem Cell Transplantation ,Humans ,Leukemia ,Myeloid ,Acute ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Retrospective Studies ,Transplantation Conditioning ,Transplantation ,Homologous ,Acute Leukemia Committee of the CIBMTR ,Cardiorespiratory Medicine and Haematology ,Immunology ,Cardiovascular medicine and haematology - Abstract
Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia (ALL). To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative ALL in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to the Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. The leukemia-free survival and overall survival rates at 5 years after transplantation in patients with abnormal cytogenetics were 40% and 42%, respectively, which were similar to those in patients with a normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (P=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse [hazard ratio (HR)=2.11; 95% confidence interval (95% CI): 1.04-4.27] and treatment failure (HR=1.97; 95% CI: 1.20-3.24). Complex karyotype was prognostic for relapse (HR=1.69; 95% CI: 1.06-2.69), whereas t(8;14) predicted treatment failure (HR=2.85; 95% CI: 1.35-6.02) and overall mortality (HR=3.03; 95% CI: 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse [monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy], intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (P=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities in ALL can be overcome by transplantation, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.
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- 2020
4. Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission.
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Rashidi, Armin, Hamadani, Mehdi, Zhang, Mei-Jie, Wang, Hai-Lin, Abdel-Azim, Hisham, Aljurf, Mahmoud, Assal, Amer, Bajel, Ashish, Bashey, Asad, Battiwalla, Minoo, Beitinjaneh, Amer, Bejanyan, Nelli, Bhatt, Vijaya, Bolaños-Meade, Javier, Byrne, Michael, Cahn, Jean-Yves, Cairo, Mitchell, Ciurea, Stefan, Copelan, Edward, Cutler, Corey, Daly, Andrew, Diaz, Miguel-Angel, Farhadfar, Nosha, Gale, Robert, Ganguly, Siddhartha, Grunwald, Michael, Hahn, Theresa, Hashmi, Shahrukh, Hildebrandt, Gerhard, Holland, H, Hossain, Nasheed, Kanakry, Christopher, Kharfan-Dabaja, Mohamed, Khera, Nandita, Koc, Yener, Lazarus, Hillard, Lee, Jong-Wook, Maertens, Johan, Martino, Rodrigo, McGuirk, Joseph, Munker, Reinhold, Murthy, Hemant, Nakamura, Ryotaro, Nathan, Sunita, Nishihori, Taiga, Palmisiano, Neil, Patel, Sagar, Pidala, Joseph, Olin, Rebecca, Olsson, Richard, Oran, Betul, Ringden, Olov, Rizzieri, David, Rowe, Jacob, Savoie, Mary, Schultz, Kirk, Seo, Sachiko, Shaffer, Brian, Singh, Anurag, Solh, Melhem, Stockerl-Goldstein, Keith, Verdonck, Leo, Wagner, John, Waller, Edmund, De Lima, Marcos, Sandmaier, Brenda, Litzow, Mark, Weisdorf, Dan, Romee, Rizwan, and Saber, Wael
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Adolescent ,Adult ,Aged ,Blood Donors ,Bone Marrow Transplantation ,Calcineurin Inhibitors ,Chronic Disease ,Cyclophosphamide ,Disease-Free Survival ,Female ,Graft vs Host Disease ,Hematopoietic Stem Cell Transplantation ,Humans ,Immunosuppressive Agents ,Incidence ,Leukemia ,Myeloid ,Acute ,Male ,Middle Aged ,Recurrence ,Remission Induction ,Retrospective Studies ,Siblings ,Survival Analysis ,Transplantation Conditioning ,Transplantation ,Haploidentical ,Young Adult - Abstract
HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) has improved donor availability. However, a matched sibling donor (MSD) is still considered the optimal donor. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes after Haplo-HCT vs MSD in patients with acute myeloid leukemia (AML) in first complete remission (CR1). Data from 1205 adult CR1 AML patients (2008-2015) were analyzed. A total of 336 patients underwent PT-Cy-based Haplo-HCT and 869 underwent MSD using calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis. The Haplo-HCT group included more reduced-intensity conditioning (65% vs 30%) and bone marrow grafts (62% vs 7%), consistent with current practice. In multivariable analysis, Haplo-HCT and MSD groups were not different with regard to overall survival (P = .15), leukemia-free survival (P = .50), nonrelapse mortality (P = .16), relapse (P = .90), or grade II-IV acute GVHD (P = .98). However, the Haplo-HCT group had a significantly lower rate of chronic GVHD (hazard ratio, 0.38; 95% confidence interval, 0.30-0.48; P < .001). Results of subgroup analyses by conditioning intensity and graft source suggested that the reduced incidence of chronic GVHD in Haplo-HCT is not limited to a specific graft source or conditioning intensity. Center effect and minimal residual disease-donor type interaction were not predictors of outcome. Our results indicate a lower rate of chronic GVHD after PT-Cy-based Haplo-HCT vs MSD using calcineurin inhibitor-based GVHD prophylaxis, but similar other outcomes, in patients with AML in CR1. Haplo-HCT is a viable alternative to MSD in these patients.
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- 2019
5. Narsoplimab, a Mannan-Binding Lectin-Associated Serine Protease-2 Inhibitor, for the Treatment of Adult Hematopoietic Stem-Cell Transplantation-Associated Thrombotic Microangiopathy
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Khaled, Samer K, Claes, Kathleen, Goh, Yeow Tee, Kwong, Yok Lam, Leung, Nelson, Mendrek, Wlodzimierz, Nakamura, Ryotaro, Sathar, Jameela, Ng, Edmund, Nangia, Narinder, Whitaker, Steve, and Rambaldi, Alessandro
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Adult ,Cancer Research ,Oncology ,Thrombotic Microangiopathies ,immune system diseases ,Hematopoietic Stem Cell Transplantation ,Antibodies, Monoclonal ,Humans ,OMS721-TMA-001 Study Group Members ,Serine Proteases ,Antibodies, Monoclonal, Humanized ,Mannose-Binding Lectin ,Biomarkers - Abstract
PURPOSE Hematopoietic stem-cell transplantation–associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with significant mortality and no approved therapy. HSCT-TMA results from endothelial injury, which activates the lectin pathway of complement. Narsoplimab (OMS721), an inhibitor of mannan-binding lectin-associated serine protease-2 (MASP-2), was evaluated for safety and efficacy in adults with HSCT-TMA. METHODS In this single-arm open-label pivotal trial ( NCT02222545 ), patients received intravenous narsoplimab once weekly for 4-8 weeks. The primary end point (response rate) required clinical improvement in two categories: (1) laboratory TMA markers (both platelet count and lactate dehydrogenase) and (2) organ function or freedom from transfusion. Patients receiving at least one dose (full analysis set [FAS]; N = 28) were analyzed. RESULTS The response rate was 61% in the FAS population. Similar responses were observed across all patient subgroups defined by baseline features, HSCT characteristics, and HSCT complications. Improvement in organ function occurred in 74% of patients in the FAS population. One-hundred-day survival after HSCT-TMA diagnosis was 68% and 94% in FAS population and responders, respectively, whereas median overall survival was 274 days in the FAS population. Narsoplimab was well tolerated, and adverse events were typical of this population, with no apparent safety signal of concern. CONCLUSION In this study, narsoplimab treatment was safe, significantly improved laboratory TMA markers, and resulted in clinical response and favorable overall survival.
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- 2022
6. Impact of Sarcopenia on Adverse Outcomes After Allogeneic Hematopoietic Cell Transplantation.
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Armenian, Saro H, Xiao, Meisi, Teh, Jennifer Berano, Lee, Brandyn, Chang, Howard A, Mascarenhas, Kristen, Lee, Sean, Iukuridze, Alex, Xie, Jack J, Scott, Jessica M, Jones, Lee W, Wong, F Lennie, Forman, Stephen J, Nakamura, Ryotaro, Berano Teh, Jennifer, and Lennie Wong, F
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CELL transplantation ,SARCOPENIA ,HEMATOPOIETIC stem cell transplantation ,MUSCLE mass ,DISABILITIES ,MYELODYSPLASTIC syndromes - Abstract
Background: High intensity treatments such as hematopoietic cell transplantation (HCT) can be curative for patients with hematologic malignancies, but this needs to be balanced by the high risk of nonrelapse mortality (NRM) during the first 2 years after HCT. Sarcopenia (low muscle mass) is associated with physical disability and premature mortality in individuals with nonmalignant diseases and may be a predictor of NRM and poor overall survival in patients undergoing HCT.Methods: This was a retrospective cohort study of 859 patients with acute leukemia or myelodysplastic syndrome who underwent a first HCT as adults (≥18 years) between 2007 and 2014. Sarcopenia was assessed from pre-HCT abdominal computed tomography scans. Two-year cumulative incidence of NRM was calculated, with relapse/progression considered as a competing risk event. Fine-Gray subdistribution hazard ratio estimates and 95% confidence intervals (CI) were obtained and adjusted for relevant covariates. Kaplan-Meier method was used to examine overall survival. All statistical tests were two-sided.Results: Median age at HCT was 51 years (range = 18-74 years); 52.5% had a high [≥3] HCT-comorbidity index; 33.7% had sarcopenia pre-HCT. Sarcopenia was an independent predictor of higher NRM risk (hazard ratio = 1.58, 95% CI = 1.16 to 2.16) compared with patients who were not. The 2-year incidence of NRM approached 30% in patients with sarcopenia and high (≥3) HCT-comorbidity index. Patients with sarcopenia had on average a longer hospitalization (37.2 days vs 31.5 days, P < .001) and inferior overall survival at 2 years (55.2%, 95% CI = 49.5% to 61.0% vs 66.9%, 95% CI = 63.0% to 70.8%, P < .001).Conclusions: Sarcopenia is an important and independent predictor of survival after HCT, with potential additional downstream impacts on health-economic outcomes. This information can be used to facilitate treatment decisions prior to HCT and guide interventions to decrease the risk of treatment-related complications after HCT. [ABSTRACT FROM AUTHOR]- Published
- 2019
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7. Expression of Activating KIR2DS2 and KIR2DS4 genes following hematopoietic cell transplant (HCT): relevance to cytomegalovirus (CMV) infection
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Gallez-Hawkins, Ghislaine M., Franck, Anne E., Li, Xiuli, Thao, Lia, Oki, Arisa, Gendzekhadze, Ketevan, Dagis, Andrew, Palmer, Joycelynne, Nakamura, Ryotaro, Forman, Stephen J., Senitzer, David, and Zaia, John A.
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Adult ,Male ,surgical procedures, operative ,Receptors, KIR ,Cytomegalovirus Infections ,Hematopoietic Stem Cell Transplantation ,virus diseases ,Humans ,Transplantation, Homologous ,Female ,Virus Activation ,RNA, Messenger ,Article - Abstract
The important role of activating killer immunoglobulin-like receptors (KIRs) in protecting against cytomegalovirus (CMV) reactivation has been described previously in patients undergoing hematopoietic cell transplantation (HCT). More specifically, the presence of multiple activating KIRs and the presence of at least KIR2DS2 and KIR2DS4 in the donor genotype identified a group of HCT patients at low risk for CMV reactivation. However, CMV infection still occurs in patients with the KIR protective genotype, and the question has been raised as to whether this is related to the lack of KIR expression. In this report, expression of the KIR2DS2 and KIR2DS4 genes, as measured by mRNA-based quantitative polymerase chain reaction in both the donor cells and the HCT recipient cells, was studied relative to CMV reactivation. In the control samples from healthy donors, the median range for KIR2DS2 and KIR2DS4 expression was low, with 35% of donors considered null-expressers. Interestingly, KIR2DS2 and KIR2DS4 expression was elevated after HCT compared with donor expression before HCT, and was significantly elevated in CMV viremic compared with CMV nonviremic HCT recipients. The CMV seropositivity of donors was not associated with activating KIR expression, and donor null expression in those with the KIR2DS2 or KIR2DS4 genotype was not predictive for CMV reactivation in the recipient. After controlling for other transplant factors, including donor type (sibling or unrelated), transplant source (bone marrow or peripheral blood stem cells), and acute GVHD grade, regression analysis of elevated KIR gene expression found an association for both KIR2DS2 and KIR2DS4, with a 7-fold increase in risk for CMV reactivation. We speculate that the elevated activating KIR expression in CMV-viremic HCT recipients is either coincidental with factors that activate CMV or is initiated by CMV or cellular processes responsive to such CMV infection reactivation.
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- 2011
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