A Single Center Experience of Haploidentical Stem Cell Transplants in Pediatric Diseases

In Asia, where the chance of finding a HLA 10/10 allele matched adult donor in a short time is low; stem cell donors including mismatched unrelated cord blood and family haploidentical stem cell donors are feasible alternatives. Between Jan 2007 and Sep 2013, a total of 14 haploidentical stem cell transplants (SCT) in 13 patients were performed in our Pediatric SCT Program. Of the 9 boys and 4 girls, SCT was performed in 2 for non-malignant diseases (1 Hurler's, 1 Hepatitis Associated Severe Aplastic Anemia) and 11 for very high risks malignancies (4 ALL, 3 AML, 3 Lymphoma, 1 MDS/RAEB). Preparative regimen was tailored to pre-morbid status and was reduced intensity (N=6) which included single TBI 2 Gy ± Fludarabine/ Cyclophosphamide or full preparation (N=8) with Fludarabine, Thiotepa, Melphalan, ATG (Thymoglobulin), Rituximab and TLI 6-8Gy or TBI 6Gy. Ex-vivo T cell depletion using either CD3 (N=6) or TCRab (N=4) depletion was performed in 10 SCT and CD34 positive selection in 1. The other 3 patients received T-replete SCT with post-transplant cyclophosphamide as per Hopkins protocol. For the 11 T-deplete SCT, the median CD34 (x10⁶/kg) was 8.8 (range, 3.4-24.2) and CD3 (x10⁴/kg) was 5 (range, 0-11). For the 3 T-replete SCT, the median TNC (x10⁸/kg) was 2.9 (range, 2.9-4.2); CD34 (x10⁶/kg) was 3.9 (range, 1.4-5.5) and CD3 (x10⁸/kg) was 0.4 (range, 0.2-2.9). For the 2 patients with non-malignant diseases, both suffered secondary graft failure, auto-reconstituted and survived. For the 11 patients with high risk cancers; 6 had progressive disease at time of SCT; 4 are surviving (1 in remission, 3 with disease) and 2 died of disease. Of the 5 patients entering SCT in remission; 3 are alive and in remission; 1 died of disease and another of regimen-related toxicity. In 11 T-deplete SCT, viral reactivations of CMV, Adenovirus, EBV, BK virus occurred in 8, 3, 3, and 2 patients, respectively. The preliminary experience of haploidentical SCT in our small cohort of patients is encouraging with no infective mortality and good engraftment rates even for patients entering SCT with bulky disease. ‘Graft versus leukemia/ lymphoma' effects are evident and may be exploited further through adoptive cell therapy in post-transplant settings to achieve more durable remissions.