Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results

Abstract

Graft failure was analyzed in 625 patients receiving allogeneic bone marrow transplants from HLA-identical sibling donors as treatment for severe aplastic anemia. Sixty-eight (11%) had no or only transient engraftment. Second bone marrow transplants were successful in achieving extended survival in 16 of 27 patients with transient initial engraftment but in none of ten patients with no sign of engraftment after the first transplant. The major factors associated with a reduced risk of graft failure were use of radiation for pretransplant immunosuppression and use of cyclosporine rather than methotrexate or T- cell depletion of the donor bone marrow for prophylaxis against graft-v- host disease (GVHD). Among 266 patients prepared for transplantation with cyclophosphamide alone, the risk of graft failure was increased in patients who received previous transfusions and reduced in those who received corticosteroids for previous therapy. Neither cell dose nor administration of donor buffy coat cells affected the probability of engraftment. Although use of radiation in conditioning reduced graft failure, survival was not improved. Posttransplant treatment with cyclosporine and avoidance of pretransplant blood transfusions were associated with improved survival.

Fludarabine based reduced intensity conditioning regimens in children undergoing allogeneic stem cell transplantation for severe aplastic anemia

“…All tested negative for FanconiÕs anemia using stress cytogenetics. The median time from diagnosis to HSCT was six months (range: [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and the median number of transfusions prior to HSCT was 14 (range: 5-42). At the time of HSCT, four patients (28.5%) were considered to be at high risk (three patients with previously failed ALG and invasive fungal infection in one patient).…”

Alemtuzumab based reduced intensity transplantation for pediatric severe aplastic anemia

“…Unrelated donor (URD) HCT is generally pursued if IST fails, as HCT toxicities include graft-versus-host disease (GVHD) and treatment related mortality (TRM) [5].The intensity of conditioning for HCT is dictated by the risk of graft rejection (GR) which is dependent on host factors and graft source. The use of HLA-mismatched donors, cord products, multiple transfusions, iron overload, and infections are associated with increased GR, GVHD, and TRM [6,7]. Conventional myeloablative regimens can overcome GR but can cause regimen-related toxicities, infertility, and malignant transformation.…”

Serial chimerism analyses indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): indication for routine assessment of chimerism post SCT for SAA

“…This is subsequently followed by a recurrence of pancytopenia and a loss of donor-derived haematopoiesis. Here the prognosis is considerably better and a number of these patients may benefit either from re-introduction of immunosuppression or a second SCT (Champlin et al, 1989;Stratford May et al, 1993;McCann et al, 2000). Autologous recovery is the recovery of normal or near normal haematopoiesis i.e.…”