Allogeneic Transplant In Children with Severe Aplastic Anemia – Excellent Outcomes with the Use of a Fludarabine Based Conditioning Regimen

Abstract 3519

There is limited data on the use of fludarabine based conditioning regimen in children with aplastic anemia though these regimens are increasingly being used in developing countries. Thirty four children (aged < 15 years) including 21 males and 13 females with a median age of 8 years (range: 2–15) underwent allogeneic transplant (HSCT) at our centre between 2004 and 2010 using HLA identical sibling or family donors. The median time from diagnosis to HSCT was 5 months (range: 2–96) and the median number of transfusions prior to HSCT was 10 (range: 3– 64). Five patients (14.7%) had failed treatment with Antithymocyte globulin (ATG) and 4 (11.4%) had an intracranial bleed in the 3 months prior to HSCT. Conditioning regimen consisted of Fludarabine 150 mg/m² over 5 days and Cyclophosphamide 120 mg/kg over 2 days. Antithymocyte globulin (ATGAM) [10 mg/kg/day for 4 days] was used in 9 patients. Graft source consisted of either bone marrow [9 patients] or G-CSF stimulated peripheral blood stem cells (PBSC)[25 patients]. Graft versus host disease (GVHD) prophylaxis consisted of Cyclosporine and short course methotrexate. The median cell doses infused were 4.9 × 10⁸ TNC/Kg for bone marrow and 8.5 × 10⁸ MNC/Kg for PBSC. Thirty patients (88.2%) engrafted while 2 (5.8%) had primary graft failure. Two children died on Day 0 and Day +5 respectively due to infection. The median time to neutrophil engraftment was 14 days (range: 8–19) while the median time to platelet engraftment was 12 days (range: 7–24). Two patients (5.8%) developed veno-occlusive disease (VOD) of the liver while none developed hemorrhagic cystitis. Acute graft versus host disease (GVHD) was seen in 7 patients (23.3%) and was grade 1–2 in all patients. Chronic GVHD was seen in 31% of patients who could be evaluated and was limited in nature in a majority of patients. Of the 2 patients with primary graft failure, one was rescued with a second transplant while the second expired due to fungal pneumonia. The Day 100 mortality was 14.1%. Secondary graft failure was seen in 1 patient but was rescued with a second transplant using the same donor. At a median follow up of 30 months (range: 1 –67), 29 patients are alive for a 3 year OS of 85.1%. Fludarabine based conditioning regimens are associated with favorable outcomes in Indian children with aplastic anemia. These results are superior to an OS of 37% with the use of ATG and Cyclosporine in a similar population (George B et al PHO March 2010).