Allogeneic hematopoietic stem cell transplantation outcomes in pediatric patients with refractory acute myeloid leukemia

Hematopoietic stem cell transplantation (HSCT) is known to be most effective in cancer patients in remission. In this paper, we analyzed a cohort of children with refractory acute myeloid leukemia (AML) in order to study the effectiveness of HSCT in such patients. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology and was conducted in accordance with the principles of the Declaration of Helsinki. All the patients and/or their legal representatives signed an informed consent form for participation in the study. Our retrospective analysis included 69 patients with refractory AML (induction failure (n = 31), refractory relapse (n = 38)) whose median age was 9.4 (1.1–22) years and who had undergone HSCT between February 2012 and January 2020, with the median follow-up of 5.47 (1.9–8.9) years. Fifty patients were transplanted from haploidentical donors, 10 – from matched related donors, 9 – from matched unrelated donors. All the patients received treosulfan-based conditioning and either melphalan or thiotepa. Fifty-five cases received TCRab+/CD19+-depleted HSCs (CliniMACS), 11 patients received native bone marrow and 2 – unrelated umbilical cord blood. For post-transplant relapse prevention, 21 patients were treated with hypomethylating agents in combination with bortezomib and 48 patients received modified donor lymphocyte infusions. Primary engraftment was achieved in 66 out of 69 patients (3 patients had died before engraftment). By Day +30, 86% of patients showed complete chimerism. The cumulative incidence of grade II–IV acute graft-versus-host disease was 42%, chronic graft-versushost disease was diagnosed in 17 pts. In the entire cohort, transplant-related mortality was 7.8% and cumulative incidence of relapse was 53%. NK cell recovery by Day +30 was significantly associated with decreased incidence of relapse: patients whose absolute NK cell counts were below the median had a cumulative incidence of relapse of 76% versus 43% in patients with NK cell counts above the median (p = 0.013). At a median follow-up of 5.5 years, the event-free survival was 37 ± 11%, and the overall survival was 42 ± 10%. Remission was achieved in 86% of the patients, while long-term overall survival reached about 40%. Our findings suggest that allogeneic HSCT provides a reasonable chance of cure in children with refractory AML and creates a solid basis for further improvement. Tumor burden in the bone marrow before conditioning and early post-transplant NK cell counts in the blood were found to be the most significant prognostic factors in HSCT.