1.
Haplo-identical or mismatched unrelated donor hematopoietic cell transplantation for Fanconi anemia: results from the Severe Aplastic Anemia Working Party of the EBMT
Zubicaray, J., Pagliara, D., Sevilla, J., Eikema, D. J., Bosman, P., Ayas, M., Zecca, M., Yesilipek, A., Kansoy, S., Renard, C., et al
American journal of hematology. 2021
Abstract
Allogeneic hematopoietic cell transplantation (HCT) is the only curative option for bone marrow failure or hematopoietic malignant diseases for Fanconi anemia (FA) patients. Although results have improved over the last decades, reaching more than 90% survival when a human leukocyte antigen (HLA)-identical donor is available, alternative HCT donors are still less reported. We compared HCT outcomes using HLA-mismatched unrelated donors (MMUD; n=123) or haplo-identical donors (HDs), either using only in vivo T cell depletion (n=33) or T cells depleted in-vivo with some type of graft manipulation ex-vivo (n=59) performed for FA between 2000 and 2018. Overall survival (OS) by 24 months was 62% (53-71%) for MMUD, versus 80% (66-95%) for HDs with only in vivo T cell depletion and 60% (47-73%) for HDs with in vivo and ex vivo T cell depletion (p 0.22). Event free survival (EFS) was better for HD-transplanted FA patients with only in vivo T cell depletion 86% (73-99%) than for those transplanted from a MMUD 58% (48-68%) or those with graft manipulation 56% (42-69%) (p=?0.046). Grade II-IV acute graft-versus-host disease (GVHD) was 41% (MMUD) versus 40% (HDs with no graft manipulation) versus 17% (HDs with T cell depleted graft), (p=0.005). No differences were found for the other transplant related outcomes. These data suggest that HDs might be considered as an alternative option for FA patients with better EFS using unmanipulated grafts. This article is protected by copyright. All rights reserved.
2.
Results of Allogenic Hematopoietic Stem Cell Transplantation in Fanconi Anemia due to Bone Marrow Failure; Single Regimen, Single Center Experience of 14 years
Gulen, T., Deniz, O., Elif, G., Kupesiz, A.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
BACKGROUND Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure (BMF) in patients with Fanconi anemia (FA). METHODS We retrospectively analyzed the records of FA patients who underwent HSCT with a radiation-free, reduced-intensity conditioning regimen (fludarabine, cyclophosphamide, and anti-thymocyte globulin) along with an unmanipulated graft infusion between 2004 and 2018. RESULTS A total of 44 patients underwent HSCT during the study period. Median age at transplantation was 121 months. Regarding the donor source, 22 transplants (50%) were collected from matched related donors (MRD) and 22 transplants (50%) were collected from alternative donors (AD). The median infused CD34+ cell dose was 4.7x10(6)/kg (range: 0.8-23) in bone marrow or peripheral blood stem cell recipients and 1.2x10(5)/kg (range: 1.1-3.6) in umbilical cord blood recipients. All but 2 patients achieved primary neutrophil engraftment (95%). In a median follow-up of 36 months (range: 1-159), 3-year overall survival was 70.5% in the entire group and 91% in the MRD recipients. Primary causes of death were infections (n=5), acute grade 3-4 graft-versus-host disease (n=4), and hemorrhagic cystitis (n=3). All surviving patients have full (n=29) and acceptable mixed (n=2) donor chimerism and good clinical status. CONCLUSION Our results showed an excellent outcome with unmanipulated grafts using a fludarabine-based, radiation-free preparative regimen for MRD recipients. Even though primary neutrophil engraftment rates were good in AD recipients, intervening complications increased mortality in these patients. In clinics where T cell depletion is not feasible, more effort is warranted to improve outcomes for AD recipients.