HLA-haploidentical TCRαβ+/CD19+-depleted stem cell transplantation in children and young adults with Fanconi anemia

Abstract

We report on the outcome of 24 patients with Fanconi anemia (FA) lacking an HLA matched related or unrelated donor, given an HLA-haploidentical T-cell receptor αβ (TCRαβ+) and CD19+ cell-depleted hematopoietic stem cell transplantation (HSCT) in the context of a prospective, single-center phase 2 trial. Sustained primary engraftment was achieved in 22 (91.6%) of 24 patients, with median time to neutrophil recovery of 12 days (range, 9-15 days) and platelet recovery of 10 days (range, 7-14 days). Cumulative incidences of grade 1 to 2 acute graft-versus-host disease (GVHD) and chronic GVHD were 17.4% (95% confidence interval [CI], 5.5%-35.5%) and 5.5% (95% CI, 0.8%-33.4%), respectively. The conditioning regimen, which included fludarabine, low-dose cyclophosphamide and, in most patients, single-dose irradiation was well tolerated; no fatal transplant-related toxicity was observed. With a median follow-up of 5.2 years (range, 0.3-8.7 years), the overall and event-free survival probabilities were 100% and 86.3% (95% CI, 62.8%-95.4%), respectively (2 graft failures and 1 case of poor graft function were considered as events). The 2 patients who experienced primary graft failure underwent a subsequent successful HSCT from the other parent. This is the first report of FA patients given TCRαβ+/CD19+-depleted haplo-HSCT in the context of a prospective trial, and the largest series of T-cell–depleted haplo-HSCT in FA reported to date. This trial was registered at www.clinicaltrials.gov as #NCT01810120.

TCRαβ/CD19 depleted HSCT from an HLA-haploidentical relative to treat children with different nonmalignant disorders

“…In line with this observation, we recently reported a low incidence of GVHD, resulting in excellent outcomes in 24 FA patients treated with this type of haplo-HSCT platform. 34 Moreover, the GRFS probability, which is used as a surrogate for quality of life, is remarkably high in our cohort.…”

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

“…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]. These results suggest unrelated CBT and haploidentical HCT as promising strategies; however, these procedures should be performed in experienced centers [14][15][16]21].…”