Peripheral Blood Stem Cell Transplant in Aplastic Anemia

Objective: We studied the outcome of heavily pre transfused aplastic anemia patients receiving peripheral blood stem cell transplant (PBSCT) from matched sibling donor.

Material: 72 consecutive blood/marrow stem cell transplants in 69 aplastic anemia patients over a period of 10 years in non HEPA filtered single rooms were recorded. Fludarabine 30 mg/m^2 D-10 to D-5, cyclophosphamide 60 mg/kg/day D-6 to D-5 and antithymocyte globulin 30 mg/kg/day D-4 to D-1 were used as conditioning regimen. Cyclosporine and methotrexate were used for graft versus host disease (GvHD) prophylaxis. ABO mismatched marrows underwent RBC depletion. No attempt to reduce antibody titres was done for ABO mismatched PBSCT.

Results: 63 patients underwent PBSCT; 2 underwent the procedure twice, 1 of whom had relapsed as acute myeloid leukemia. Of the 6 patients who received bone marrow stem cells, 2 relapsed and 1 underwent a successful PBSCT from the same donor. The median age of patients was 30 years (range 4-40 years); median time to transplant was 13.5 months (range 1-65 months); median transfusions before transplant was 22.5 (range 3-10). 28 (38.8%) patients had pre-existing infections at time of transplant. 65 patients received empirical antibiotics and 27 received empirical antifungals for febrile neutropenia during transplant. Positive blood culture for bacteria was recorded in 10 patients and a biopsy proven fungus (2 aspergillus, 2 mucor) in 4 patients; 5 other patients had possible fungal infection based on radiological features.

All patients and donors were CMV IgG positive at baseline. CMV reactivation was noted in 11 patients, 5 of whom were on steroids for GVHD; 3 patients subsequently suffered a graft failure.

55/72 (76%) patients are alive at median follow up of 60 months ranging from 0-118 months. Acute GVHD was seen in 18/72 transplants (25%). 5 patients developed grade III-IV gut acute GvHD; 4 died. Chronic GvHD was seen in the 32% cases (20/62; 10 patients died before day 100). However these were mostly associated with dry skin and changes in pigmentation which generally subsided over time and well tolerated;1 patient had nephrotic syndrome at 3 years. Severe cGVHD as per NIH criteria was seen in only 5 patients. 17 patients had ABO major mismatch of which 5 patients developed PRCA. PRCA was managed with steroids and erythropoietin; the longest duration before recovery was 12 months.  17 patients died. Cause of early death (<day 100) were: acute GVHD 4, intracranial bleed 4, aspergillus 1, CMV 1, graft rejection 5 (more than 1 possible cause in some). Cause of death > day 100: chronic GVHD 1, graft rejection 2, tuberculosis 1.

Conclusions: PBSCT is safe in aplastic anemia patients whose transplant has been delayed and thereby heavily pretransfused. The outcome and survival appears comparable to those achieved with historical bone marrow transplant data without apparent increase in morbidity on account of chronic GvHD.