HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with Fanconi anemia.

Abstract

We report the outcome of 12 consecutive pediatric patients with Fanconi anemia (FA) who had neither an HLA-identical sibling nor an HLA-matched unrelated donor and who were given T cell-depleted, CD34(+) positively selected cells from a haploidentical related donor after a reduced-intensity, fludarabine-based conditioning regimen. Engraftment was achieved in 9 of 12 patients (75%), and the cumulative incidence of graft rejection was 17% (95% confidence interval [CI], 5% to 59%). Cumulative incidences of grades II to IV acute and chronic graft-versus-host disease were 17% (95% CI, 5% to 59%) and 35% (95% CI, 14% to 89%), respectively. The conditioning regimen was well tolerated, with no fatal regimen-related toxicity and 3 cases of grade III regimen-related toxicity. The cumulative incidence of transplant-related mortality was 17% (95% CI, 5% to 59%). The 5-year overall survival, event-free survival, and disease-free survival were 83% (95% CI, 62% to 100%), 67% (95% CI, 40% to 93%), and 83% (95% CI, 62% to 100%), respectively. These data demonstrate that a fludarabine-based conditioning regimen, followed by infusion of high doses of T cell-depleted stem cells, is able to ensure engraftment with good overall survival and disease-free survival, confirming the feasibility of haploidentical hematopoietic stem cell transplantation in FA. To the best of our knowledge, this is the largest series of hematopoietic stem cell transplantation from a haploidentical related donor in FA patients reported to date.

• Authors: Marco Zecca, Luisa Strocchio, Daria Pagliara, Patrizia Comoli, Alice Bertaina, Giovanna Giorgiani, Cesare Perotti, Franco Corbella, Letizia Brescia, Franco Locatelli
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 20 Issue 4 Pg. 571-6 (Apr 2014) ISSN: 1523-6536 [Electronic] United States
• PMID: 24462983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD34
• HLA Antigens
• Myeloablative Agonists
• Vidarabine
• fludarabine

Topics

• Adolescent
• Antigens, CD34 (immunology)
• Child
• Fanconi Anemia (immunology, mortality, pathology, therapy)
• Female
• Graft Survival
• Graft vs Host Disease (immunology, mortality, pathology)
• HLA Antigens (immunology)
• Hematopoietic Stem Cell Transplantation
• Histocompatibility Testing
• Humans
• Lymphocyte Depletion
• Male
• Myeloablative Agonists (therapeutic use)
• Prospective Studies
• Survival Analysis
• T-Lymphocytes (cytology, immunology)
• Transplantation Conditioning
• Transplantation, Homologous
• Treatment Outcome
• Unrelated Donors
• Vidarabine (analogs & derivatives, therapeutic use)