Wagner J.E.,University of Minnesota |
Seminars in Hematology | Year: 2010
In October 1988, the world's first umbilical cord blood transplant (UCBT) was performed. Despite considerable skepticism initially by both scientists and clinical specialists in the field, umbilical cord blood (UCB) has now become one of the most commonly used sources of hematopoietic stem cells (HSCs) for allogeneic transplantation. Today, an estimated 600,000 UCB units have been banked and 20,000 UCB units have been distributed worldwide for both adults and children with life-threatening malignant and nonmalignant diseases. During this first generation of UCBT, substantial advances have been made resulting in better outcomes for our patients. UCB serves as an extraordinary example of translational medicine at its best, where clinical problems compel scientists to move basic discoveries into novel therapeutic approaches. This chapter briefly summarizes the highpoints of the history of UCBT with speculations as to what the next generation of research promises to discover. © 2010 Elsevier Inc. All rights reserved.
Eapen M.,Medical College of Wisconsin |
Klein J.P.,Medical College of Wisconsin |
Sanz G.F.,Hospital Universitario La Paz |
Spellman S.,Center for International Blood and Marrow Transplant Research |
And 15 more authors.
The Lancet Oncology | Year: 2011
Background: The importance of matching at the HLA C locus has not been well defined for unrelated umbilical-cord blood transplantation. The selection algorithm for umbilical-cord blood units generally considers intermediate resolution HLA typing at A and B and allele-level typing at DRB1. We aimed to establish the relative importance of additional matching at HLA C. Methods: We used Cox regression to assess retrospectively the effect of donor-recipient HLA matching on outcomes of single umbilical-cord blood transplantations for leukaemia and myelodysplastic syndrome. Our primary endpoint was transplant-related mortality. HLA typing was done with molecular techniques with a minimum of intermediate resolution for HLA A, B, and C, and at the allele-level for DRB1. Findings: The median age of our study population was 10 years (range <1-62) and 552 (69%) of 803 patients were aged 16 years or younger at transplantation. Compared with transplantations matched at HLA A, B, C, and DRB1 (n=69), transplant-related mortality risk was higher after transplantations matched at HLA A, B, and DRB1 and mismatched at HLA C (n=23; HR 3·97, 95% CI 1·27-12·40; p=0·018). Transplant-related mortality risk was also higher after transplantations with a single mismatch at HLA A, B, or DRB1 and mismatched at HLA C (n=234; 1·70, 1·06-2·74; p=0·029) compared with transplantations matched at HLA C with a single mismatch at HLA A, B, or DRB1 (n=127). Assessing the overall effect of HLA disparity on transplant-related mortality, risks were higher with units mismatched at two (n=259; 3·27, 1·42-7·54; p=0·006), three (n=253; 3·34, 1·45-7·71; p=0·005), or four (n=75; 3·51, 1·44-8·58; p=0·006) loci compared with matched units (n=69). Interpretation: Our data suggest that the present strategy for umbilical-cord blood unit selection should be reassessed; matching at HLA C for units that are matched at HLA A, B, or DRB1 or in the presence of a single locus mismatch at HLA A, B, or DRB1 should be included to minimise mortality risks. Funding: National Cancer Institute, National Heart Lung and Blood Institute, National Institute for Allergy and Infectious Diseases, Leukemia and Lymphoma Society, US Department of the Navy, Children's Leukemia Research Association, and INSERM. © 2011 Elsevier Ltd.
Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: A report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation
Baron F.,University of Liege |
Labopin M.,HOpital Saint Antoine |
Niederwieser D.,University of Leipzig |
Vigouroux S.,University of Bordeaux Segalen |
And 12 more authors.
Leukemia | Year: 2012
This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P<0.0.001) owing to high risk of nonrelapse mortality (NRM; HR=5.2, P<0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR=0.72; P=0.07) translating into a better OS (HR=1.8; P<0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR=0.65; P=0.02) but also with higher NRM (HR=3.5; P<0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P<0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR=0.65; P=0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD. © 2012 Macmillan Publishers Limited. All rights reserved.
Eapen M.,Center for International Blood and Marrow Transplant Research |
Klein J.P.,Center for International Blood and Marrow Transplant Research |
Klein J.P.,Medical College of Wisconsin |
Ruggeri A.,Eurocord |
And 20 more authors.
Blood | Year: 2014
We studied the effect of allele-level matching at human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 in 1568 single umbilical cord blood (UCB) transplantations for hematologic malignancy. The primary end point was nonrelapse mortality (NRM). Only 7% of units were allele matched at HLA-A, -B, -C, and -DRB1; 15% were mismatched at 1, 26% at 2, 30% at 3, 16% at 4, and 5% at 5 alleles. In a subset, allele-level HLA match was assigned using imputation; concordance between HLA-match assignment and outcome correlation was confirmed between the actual and imputed HLA-match groups. Compared with HLA-matched units, neutrophil recovery was lower with mismatches at 3, 4, or 5, but not 1 or 2 alleles.NRM was higher with units mismatched at 1, 2, 3, 4, or 5 alleles compared with HLAmatched units. The observed effects are independent of cell dose and patient age. These data support allele-levelHLAmatching in the selection of single UCB units. (Blood. 2014;123(1):133-140). © 2011 by The American Society of Hematology; all rights reserved.
Locatelli F.,Istituto di Ricovero e Cura a Carattere Scientifico |
Locatelli F.,University of Pavia |
Kabbara N.,Eurocord |
Ruggeri A.,Eurocord |
And 13 more authors.
Blood | Year: 2013
We analyzed the outcomes of 485 patients with thalassemia major (TM) or sickle cell disease (SCD) receiving HLA-identical sibling cord blood transplantation (CBT, n = 96) or bone marrow transplantation (BMT, n = 389). Compared with patients given BMT, CBT recipients were significantly younger (median age 6 vs 8 years, P = .02), and were treated more recently (median year 2001 vs 1999, P < .01). A higher proportion of patients with TM belonging to classes II-III of the Pesaro classification received BMT (44%) compared with CBT (39%, P < .01). In comparison with patients receiving BMT(n = 259, TM; n = 130, SCD), those given CBT (n = 66, TM; n = 30, SCD) had slower neutrophil recovery, less acute graft-versus-host disease (GVHD) and none had extensive chronic GVHD. With a median follow-up of 70 months, the 6-year overall survival was 95% and 97% after BMT and CBT, respectively (P = .92). The 6-year disease-free survival (DFS) was 86% and 80% in TM patients after BMT and CBT, respectively, whereas DFS in SCD patients was 92% and 90%, respectively. The cell dose infused did not influence outcome of patients given CBT. In multivariate analysis, DFS did not differ between CBT and BMT recipients. Patients with TMor SCD have excellent outcomes after both HLA-identical sibling CBT and BMT. © 2013 by The American Society of Hematology.