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Mary Eapen,
John P Klein,
Guillermo F Sanz,
Stephen Spellman,
Annalisa Ruggeri,
Claudio Anasetti,
Maria Brown,
Richard E Champlin,
Joan Garcia-Lopez,
Gareth Hattersely,
Gesine Koegler,
Mary J Laughlin,
Gerard Michel, Samir K Nabhan,
Franklin O Smith,
Mary M Horowitz,
Eliane Gluckman,
Vanderson Rocha
[show abstract]
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ABSTRACT: 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.
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.
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).
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.
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.
The lancet oncology 12/2011; 12(13):1214-21. · 14.47 Impact Factor
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Samir K Nabhan,
Marco A Bitencourt,
Michel Duval,
Manuel Abecasis,
Carlo Dufour,
Karim Boudjedir,
Vanderson Rocha,
Gérard Socié,
Jakob Passweg,
Kumiko Goi,
Jean Sanders,
John Snowden,
Hiromasa Yabe,
Ricardo Pasquini,
Eliane Gluckman
[show abstract]
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ABSTRACT: Reduced fertility is one clinical manifestation among other well known Fanconi anemia features. Most recipients of allogeneic hematopoietic stem cell transplantation suffer from secondary infertility owing to gonadal damage from myeloablative conditioning. In order to evaluate the rate of pregnancy in Fanconi anemia transplanted patients, we performed a retrospective analysis of female patients transplanted in 15 centers from 1976 to 2008. Among 578 transplanted Fanconi anemia patients, we identified 285 transplanted females of whom 101 patients were aged 16 years or over. Ten became pregnant (4 twice). Before hematopoietic stem cell transplantation all had confirmed Fanconi anemia diagnosis. Median age at transplantation was 12 years (range 5-17 years). Conditioning regimen consisted of cyclophosphamide with or without irradiation. During follow up, 5 of 10 patients presented signs of ovarian failure. Among those, 2 patients spontaneously recovered regular menses, and 3 received hormonal replacement therapy. Pregnancy occurred from four to 17 years after hematopoietic stem cell transplantation. Three patients had preterm deliveries, one patient had a hysterectomy for bleeding. All 14 newborns had normal growth and development without congenital diseases. In conclusion, recovery of normal ovarian function and a viable pregnancy is a realistic but relatively rare possibility even in Fanconi anemia patients following hematopoietic stem cell transplantation. Mechanisms of fertility recovery are discussed.
Haematologica 10/2010; 95(10):1783-7. · 6.42 Impact Factor
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Andrée-Laure Herr,
Nabil Kabbara,
Carmem M S Bonfim,
Pierre Teira,
Franco Locatelli,
Karin Tiedemann,
Arjan Lankester,
Jean-Pierre Jouet,
Chiara Messina,
Yves Bertrand,
Cristina Díaz de Heredia,
Christina Peters,
Wagnara Chaves, Samir K Nabhan,
Irina Ionescu,
Eliane Gluckman,
Vanderson Rocha
[show abstract]
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ABSTRACT: We analyzed risk factors influencing outcomes after related (R) human leukocyte antigen-identical cord blood transplantation (CBT) for 147 patients with malignancies reported to Eurocord-European Group for Blood and Marrow Transplantation. CBT has been performed since 1990; median follow-up was 6.7 years. Median patient age was 5 years. Acute leukemia was the most frequent diagnosis (74%). At CBT, 40 patients had early, 70 intermediate, and 37 advanced disease. CB grafts contained a median of 4.1 × 10(7)/kg total nucleated cells (TNCs) after thawing. The cumulative incidence (CI) of neutrophil recovery was 90% at day +60. CIs of acute and chronic graft-versus-host disease (GVHD) were 12% and 10% at 2 years, respectively. At 5 years, CIs of nonrelapse mortality and relapse were 9% and 47%, respectively; the probability of disease-free survival (DFS) and overall survival were 44% and 55%, respectively. Among other factors, higher TNCs infused was associated with rapid neutrophil recovery and improved DFS. The use of methotrexate as GVHD prophylaxis decreased the CI of engraftment. Patients without advanced disease had improved DFS. These results support banking and use of CB units for RCBT. Cell dose, GVHD prophylaxis not including methotrexate, and disease status are important factors for outcomes after RCBT.
Blood 09/2010; 116(11):1849-56. · 9.90 Impact Factor
