Ten-year Experience of Allogeneic Haploidentical Hematopoietic Stem Cell Transplantation with Non-Manipulated Grafts in Children and Adolescents with High-Risk Acute Leukemia

Haploidentical transplantation (Haplo-HSCT) is an effective method for treating patients with high-risk acute leukemias (AL) who do not have HLA-matched related (MRD) and matched unrelated donors (MUD).During 10 years in R/G/Memorial Institute of children oncology, hematology and transplantation more than 150 patients have Haplo-HSCT.More than 50% of patients were «salvage group» patients. Materials and methods106 patients with high-risk AL, median age 7 y.o.(range 0-18), acute lymphoblastic leukemia (ALL) -63 (59.4%), acute myeloid leukemia (AML) -43 (40.6%), received Haplo-HSCT from December 2006 till December 2016.Forty three patients (40.6%) recived Haplo-HSCT in complete remission (CR): CR1 21 patients (49%), CR2 -13 patients (30%), CR3 -9 patients (21%).Resistance disease or resistance relapse AL -63 (59.4%) patients.Сonditioning regimens were as follows: MAC «GIAC» 39 patients (36.8%),MAC based on Busulfan 12mg/b.w. and Fludarabine 150 mg/mg(2) -2 (2%), MAC reduced toxisity based on Treosulfan 42 g/m(2) -6 (5.7%), RIC based on Melfalan 140 mg/m(2) -40 (37.7%),RIC with Busulfan 8 mg/b.w.-18 (17%).All patients received prophylaxis of acute graft versus host disease (aGVHD).Seroprophylaxis with ATG -ATGAM 60mg/b.w.-39 (36.8%), posttransplant cyclophosphomide 50 mg/b.w. on D+3, D+4 -67 (63.2%).Conventional immunosuppressive therapy: tacrolimus 47 patients (44.3%),CsA 59 patients (55.7%).Source of transplant -combined unmanipulated stimulated Haplo-bone marrow plus manipulated (positive selected CD34 + ) stimulated CD34 + cells -27 patients (25.5%) and unmanipulated stimulated Haplo-bone marrow -79 (74.5%).Stem cells dose of unmanipulated stimulated Haplo-bone marrow transplant CD34 + x10 6 /b.w.median 5.9x10(6)/b.w., stem cells dose of combined transplant median 5.9x10(6)/b.w.(range from 2.5 till 30.9х10(6)/b.w. Statistical analysisSPSS Statistics v.17.Overal survival (OS) was defined as time from study enrollment to death, with living patients censored on the date of the last follow-up.The Kaplan-Meier method was used to estimate OS rates, and the exact log-rank test was used to compare survival curves.Survival estimates are reported with standard errors determined by the method of Peto and Pike. CLINICAL STUDIES ConclusionHaplo-HSCT in 1 and 2 remissions of AL allows to achieve 10-year OS in 64.7% of children, while the type of acute leukemia does not influence the outcome of haplo-HSCT.The acceptable frequency of development of aGVHD III 0 -IV 0 -18.6% allows to treat haplo-HSCT as therapy in 1 and 2 remissions of high risk group.The main complication of haplo-HSCT is relapse -23.5% in the early posttransplant period to D + 100.