Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Using Fludarabine, Reduced-Dose Cyclophosphamide, and ATG

BACKGROUND: Although allogeneic hematopoietic stem cell transplantation (HSCT) has been widely performed for severe aplastic anemia (SAA), the standard conditioning regimen has yet to be established. Recently, the outcomes of a variety of reduced-intensity conditioning regimens using fludarabine have been reported.

AIMS: We have retrospectively evaluated the safety and efficacy of allogeneic HSCT for SAA using fludarabine, reduced-dose cyclophosphamide, and ATG.

PATIENTS & METHODS: Six patients (median age 30 (range: 22-61)) with SAA who underwent allogeneic bone marrow transplantation from an HLA-identical sibling (n=3) or an HLA-matched unrelated donor (n=3) were evaluated. Conditioning included fludarabine (120 mg/m²), cyclophosphamide (100 mg/kg), and ATG (Thymoglobulin; 3.75 mg/kg). In addition, 2 Gy of TBI (with ovarian shielding for young female patients) was delivered for heavily transfused patients or HSCT from an unrelated donor. For the prophylaxis of graft-versus-host disease (GVHD), cyclosporine A or tacrolimus with short-term methotrexate was given.

RESULTS: The transplant procedure was generally well-tolerated and there were no life-threatening complications. All patients achieved neutrophil and platelet engraftment and became transfusion independent. Full donor chimerism was confirmed on whole bone marrow cells at day 28 after transplantation. Only one patient developed acute GVHD (grade II) and none developed chronic GVHD. With a median follow-up period of 15.9 months (range: 11.6-22.4 months), all patients are alive. At 18 months after transplantation, one patient experienced progressive pancytopenia, requiring red blood cell transfusion, in spite of the full donor chiemrism both in the bone marrow and peripheral blood T cells. Chimerism analysis of the peripheral blood T cells was analyzed later than 6 months post-transplant, showing mixed chimerism in 3 patients with stable hematopoiesis. The recovery of menstruation was observed in all 4 evaluable young female patients at 3, 7, 8, and 9 months after transplantation, respectively.

CONCLUSION: These results suggest that this regimen could be a safe and effective conditioning regimen of allogeneic HSCT for SAA both from sibling and unrelated donor. However, long-term follow-up is needed to further evaluate the dynamics of T-cell chimerism and the incidence of late-onset graft failure.