Successful Rescue of Childhood Acute Leukemia In Non-Remission by Non-T-Cell Depleted HLA-Haploidentical Hematopoietic Cell Transplantation.

Abstract 4582

Refractory acute leukemia who do not achieve second or subsequent complete remission (CR) have an extremely poor prognosis. Non-T-cell depleted (TCD) HLA-haploidentical hematopoietic cell transplantation (haplo-HCT) is a form of adoptive cellular therapy that has a high degree of efficacy in hematologic malignancies. The major problems of non-TCD haplo-HCT are severe graft-versus-host disease (GVHD), graft failure (GF) and high-risk of early death. We conducted non-TCD haplo-HCT for children with acute leukemia in non-remission as a novel therapeutic strategy.

Five consecutive children under 15 (0-13) years old with hematological malignancies underwent non-TCD haplo-HCT from family donors between November 2002 and July 2010 at Fukushima Medical University Hospital. All patients were in non-remission at transplantation. One donor was mother and the other 4 donors were fathers of the patients. One patient was in 3 loci, and 4 patients were mismatched 4 loci of the allele level for HLA-A, -B, -C and -DRB1. The blast count in the marrow before transplantation was 80%, 75%, 34%, 10% and 96%, respectively. There were two acute myelogenous leukemia and three acute lymphoblastic leukemia. There were two refractory diseases to chemotherapy and three relapses after HSCT. All of them received myeloablative conditioning (2 Busulfan based, 3 TBI based). Type of graft were bone marrow in one and peripheral blood stem cell in 4. Total of 9.9 ×10⁸/kg of nucleated bone marrow cells were infused in the patient received BMT. The median number of TNC and CD34+ cell doses were 11 (8-21.4)×10⁸/kg and 7.9 (6.5-8.8)×10⁶/kg in PBSCT, respectively. GVHD prophylaxis were combination of tacrolimus, methotrexate was given in one patient, combination of tacrolimus, methotrexate and prednisolone in one, combination of tacrolimus, methotrexate, prednisolone, and antihuman thymocyte immunoglobulin (ATG) in 3.

All patients achieved primary engraftment at median of 13 days (11 -15) and achieved complete remission. Five patients developed acute GVHD, with grade 1 in two patients, grade 2 in two patients, grade 3 in one patient. Chronic GVHD occurred in 2 of 4 evaluable patients. Infectious complications including 2 CMV reactivation, 1 CMV-IP, 1 invasive aspergillosis, 1 candida sepsis were observed. One patient died from CMV-IP in remission, remaining 4 patients survived disease-free + 4, + 9, + 10 and + 94 months after non-TCD haplo-HCT, respectively.

These preliminary results suggested that non-TCD haplo-HCT is effective strategy in children with refractory leukemia.