Overcoming Graft Rejection in Adult Patients with High-Risk Severe Aplastic Anemia Using Supplemental CD34+-Enriched PBSC in Combination with BM.

The transplantation of a large number of stem cells can overcome the graft rejection with the pitfall of an increased incidence of graft-versus host disease (GVHD). We analyzed the clinical outcome of adult patients with severe aplastic anemia (SAA) at high risk for graft rejection who received a transplant with both bone marrow (BM) and CD34+-enriched peripheral blood stem cells (PBSC) to decrease the graft rejection. Between December 1999 and April 2006, 31 consecutive adult patients with SAA who were multi-transfused (more than 40 units of red blood cells ± platelets) and/or had a 3 years or longer period prior to transplant were investigated. The median age of patients was 39 years (range, 21–52) and 19 (61.3%) were women. The median interval from diagnosis to transplant was 62 months (range, 2–347). The median number of transfusions before transplant was 144 units (range, 20–680). Twenty-three (74.2%) patients received a prior immunosuppressive treatment and 3 (9.7%) prior allogeneic transplants. All patients received both BM and CD34+-enriched PBSC from sibling donors. PBSC were collected on days 5 and 6 of G-CSF (10μg/kg/day), and T cells were depleted using magnetic cell sorting (CliniMACS system, Miltenyi Biotec, Germany). Marrow harvesting was performed 48 hours after the last leukapheresis. Conditioning regimens consisted of cyclophosphamide/antithymocyte globulin + procarbazine (n=19) or fludarbine (n=9). Other 3 patients with a history of prior transplant received irradiatin based conditining regimens. GVHD prophylaxis consisted of cyclosporin and short-term methotrexate. Patients were transplanted with a median mononuclear cell dose of 1.35 (range, 0.43–4.05)×108/kg of body weight. The median CD34+ cell counts in the CD34+-enriched PBSC and unpurged BM were 7.99 (range 2.26–23.49)×106/kg and 4.41 (range, 1.34–15)×107/kg, respectively. With a median follow-up of 66 months, the 5-year probability of survival was 87.1%. The median time to neutrophils ≥0.5×109/L and platelet ≥20×109/L without platelet transfusions were 13 days (range, 10–32) and 16 days (range, 11–40), respectively. No patient developed graft failure. The cumulative incidence of acute GVHD over grade II and chronic GVHD were 9.7% and 16.1%, respectively. In conclusion, high rates of durable engraftment and excellent long-term survival were achieved by our approach which seems to play a role in overcoming the sensitization to histocompatibility antigens. Remarkably, the T-cell depleted PBSC apparently did not increase the incidence of GVHD. The high dose stem cell component therapy may be feasible for high-risk SAA adult patients.