Unrelated donor vs HLA-haploidentical α/β T-cell- and B-cell-depleted HSCT in children with acute leukemia.

Abstract

Traditionally, hematopoietic stem cell transplantation (HSCT) from both HLA-matched related and unrelated donors (UD) has been used for treating children with acute leukemia (AL) in need of an allograft. Recently, HLA-haploidentical HSCT after αβ T-cell/B-cell depletion (αβhaplo-HSCT) was shown to be effective in single-center studies. Here, we report the first multicenter retrospective analysis of 127 matched UD (MUD), 118 mismatched UD (MMUD), and 98 αβhaplo-HSCT recipients, transplanted between 2010 and 2015, in 13 Italian centers. All these AL children were transplanted in morphological remission after a myeloablative conditioning regimen. Graft failure occurred in 2% each of UD-HSCT and αβhaplo-HSCT groups. In MUD vs MMUD-HSCT recipients, the cumulative incidence of grade II to IV and grade III to IV acute graft-versus-host disease (GVHD) was 35% vs 44% and 6% vs 18%, respectively, compared with 16% and 0% in αβhaplo-HSCT recipients (P < .001). Children treated with αβhaplo-HSCT also had a significantly lower incidence of overall and extensive chronic GVHD (P < .01). Eight (6%) MUD, 32 (28%) MMUD, and 9 (9%) αβhaplo-HSCT patients died of transplant-related complications. With a median follow-up of 3.3 years, the 5-year probability of leukemia-free survival in the 3 groups was 67%, 55%, and 62%, respectively. In the 3 groups, chronic GVHD-free/relapse-free (GRFS) probability of survival was 61%, 34%, and 58%, respectively (P < .001). When compared with patients given MMUD-HSCT, αβhaplo-HSCT recipients had a lower cumulative incidence of nonrelapse mortality and a better GRFS (P < .001). These data indicate that αβhaplo-HSCT is a suitable therapeutic option for children with AL in need of transplantation, especially when an allele-matched UD is not available.

• Authors: Alice Bertaina, Marco Zecca, Barbara Buldini, Nicoletta Sacchi, Mattia Algeri, Francesco Saglio, Cesare Perotti, Anna Maria Gallina, Valentina Bertaina, Edoardo Lanino, Arcangelo Prete, Walter Barberi, Manuela Tumino, Claudio Favre, Simone Cesaro, Francesca Del Bufalo, Mimmo Ripaldi, Stella Boghen, Gabriella Casazza, Marco Rabusin, Adriana Balduzzi, Franca Fagioli, Daria Pagliara, Franco Locatelli
• Journal: Blood (Blood) Vol. 132 Issue 24 Pg. 2594-2607 (12 13 2018) ISSN: 1528-0020 [Electronic] United States
• PMID: 30348653 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by The American Society of Hematology.

Chemical References

• Receptors, Antigen, T-Cell, alpha-beta

Topics

• Acute Disease
• Adolescent
• Allografts
• B-Lymphocytes
• Child
• Child, Preschool
• Chronic Disease
• Female
• Graft vs Host Disease (mortality, prevention & control)
• Hematopoietic Stem Cell Transplantation
• Humans
• Infant
• Leukemia (mortality, therapy)
• Lymphocyte Depletion
• Male
• Receptors, Antigen, T-Cell, alpha-beta
• Retrospective Studies
• T-Lymphocytes
• Unrelated Donors