Haplo‐identical or mismatched unrelated donor hematopoietic cell transplantation for Fanconi anemia: Results from the Severe Aplastic Anemia Working Party of the EBMT

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 = .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 = .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 = .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.

Unmanipulated haploidentical haematopoietic cell transplantation with radiation‐free conditioning in Fanconi anaemia: A retrospective analysis from the Chinese Blood and Marrow Transplantation Registry Group

“…The mean (SD) cumulative incidence of 30-day neutrophil engraftment was 96.4% (0.08%), with a median (range) time of 12 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) days. The median (range) time to attaining a platelet count of ≥20 × 10 9 /L was 13 (6-180) days.…”

“…Recent decades have witnessed improved survival in HCT for FA, including haplo-HCT. [5][6][7][8][9][10][11] The long-term side-effects of HCT, especially the increased risk of secondary malignancies, have become critical considerations. In patients with FA, intrinsic DNA repair defects lead to unique hypersensitivity to irradiation and alkylating agents.…”

Recent advances in hematopoietic cell transplantation for inherited bone marrow failure syndromes

“…Several retrospective studies showed that unrelated CBT in FA was associated with a high rate of graft failure, whereas a recent study from University of Minnesota described that the rate of engraftment with unrelated CBT using fludarabine-based RIC with 3-Gy TBI was comparable to that with MRD/MUD-BMT [14,18]. As another potential stem cell source for patients with FA, the EBMT-Severe Aplastic Anemia Working Party (SAAWP) reported promising outcomes in patients who underwent haploidentical HCT with in vivo T-cell depletion, with a 2-year event-free survival (EFS) of 86% [19]. A study from Italy reported that haploidentical HCT with ex vivo depletion of T-cell receptor α/β + and CD19 + cells was successfully performed in patients with FA, with a 5-year EFS of 86% [20].…”

Fanconi anemia and haploidentical stem cell transplantation

“…Some studies have demonstrated that a total dosage of up to 60 mg/kg is safe in patients with FA 10 . Evidence of the viability of using haploidentical donors in FA has increased in recent years with excellent results 11–14 …”

“…10 Evidence of the viability of using haploidentical donors in FA has increased in recent years with excellent results. [11][12][13][14]…”