Matched sibling donor haematopoietic stem cell transplantation in Fanconi anaemia: an update of the Cincinnati Children's experience

Abstract

Summary Our results for 18 patients undergoing matched sibling donor stem cell transplant for Fanconi anaemia at Cincinnati Children's Hospital Medical Center were published in 1994. The present report updates our results in 35 consecutive patients. Thirty patients transplanted for marrow aplasia received cyclophosphamide 5 mg/kg for 4 d and 400 cGy thoraco‐abdominal irradiation. Five patients with clones involving chromosome 7, myelodysplastic syndrome or leukaemia received a more aggressive regimen with total body irradiation. Horse antithymocyte globulin was administered in the pretransplant period to promote engraftment and in the post‐transplant period for additional graft‐versus‐host disease (GVHD) prophylaxis. The median age at bone marrow transplantation was 7·6 years. Median day of engraftment was day +12 (range 9–49), eight patients developed acute GVHD and four chronic GVHD, one limited and three extensive. Twenty‐nine of 35 patients (89% actuarial survival at 10 years) had survived with a median follow up of 10·2 years; two children had developed secondary malignancy. All surviving patients had normal blood counts with full donor engraftment. These data indicate excellent long‐term outcomes and serve as a reference for newer radiation‐free preparative regimes that may reduce the risk of late secondary malignancy.

Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A

“…While clinical studies in BM transplantation settings [4][5][6] suggest that normal HSC/progenitor cells could effectively engraft to FA BM under certain immunosuppressive conditioning, mechanistic studies on whether FA HSC/progenitor cells have cellautonomous defects in hematopoietic engraftment remain lacking. Previously, we and others have demonstrated that FA hematopoietic progenitor cells show poor engraftment in mouse knockout models.…”

“…1,2 Allogeneic hematopoietic stem cell (HSC) transplantation from related and unrelated donors is the only known curative therapy for severe BM failure in patients with FA. 3,4 While outcomes from related donors seem to be good, 4 the use of unrelated donors as the HSC source has had limited success with poor survival due to graft rejection, graft-versus-host disease (GVHD), and treatment-related toxicities. The recent addition of fludarabine to the transplant preparative regimen for patients undergoing unrelated donor HSC transplantation has significantly reduced these problems, probably as a result of greatly enhanced immune suppression without overlapping toxicities.…”

Hematopoietic stem cell transplantation in patients with Fanconi anemia: the experience of the Russian Children's Clinical Hospital and the Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology

“…При этом показатели ОВ в данных исследованиях колебались от 83 до 88%, а смертность, связанная с ТГСК, -от 8 до 18,5 %. Отторжение транс-плантата зафиксировано в 8 % случаев, а РТПХ -в 12 % [23]. В одном из исследований была показана высокая доля острой РТПХ -36 % больных [24].…”

Fanconi anaemia: new strategies

“…11 Both types of conditioning regimens provided good results. As detailed in Table 1, [11][12][13] actuarial overall survival ranged between 83 and 88% with a TRM of 8-18.5%, highest failure rate of 8% and average chronic GVHD around 12%. Ac GvHD peaked to 36% in one study 12 and, along with TRM and chronic Ac GvHD, was remarkably high also in a small group of patients conditioned only with CY 80 mg/kg.…”