Primary refractory and relapsed refractory acute myeloid leukemia remains an unresolved problem in pediatric oncology. Children with AML who fail to achieve complete remission on high-dose cytarabine and antracyclines have no chance for survival without allogeneic hematopoietic stem cell transplantation. We evaluated the outcome of αβ-T-cell-depleted haploidentical transplantation in a cohort of children with chemorefractory acute myeloid leukemia. Thirty-six patients with either primary refractory (n = 14) or relapsed refractory (n = 22) acute myeloid leukemia in active disease status received a transplantation from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent treatment with treosulfan and either melphalan or thiophosphamide. Serotherapy consisted of antithymocyte globuline in 14 pts and targeted immunomodulation with tocilizumab +/- abatacept in 22 pts. Grafts were PBSCs engineered by TCR-αβ/CD19 depletion. Posttransplant preemptive therapy included modified donor lymphocyte infusions with or without hypomethylating agents. Complete remission was achieved in 30 (83%) рts. The cumulative incidence of acute GVHD grade II–IV was 25%, and the cumulative incidence of chronic GVHD was 18%. Transplant-related mortality was 6%, and relapse incidence was 48%. Event-free survival was 46%, and overall survival was 41% at 2 years. Good early recovery of NK cells was associated with significantly improved survival and decreased relapse incidence. Our data suggest that αβ-T-cell-depleted haploidentical HSCT provides a reasonable chance of cure in a cohort of children with chemorefractory acute myeloid leukemia and creates a solid basis for further improvement. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology.

Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia, in which the bone marrow produce increased numbers of immature abnormal megakaryoblasts. AMKL is rare both in children and adults, but is the most frequent subtype of acute myeloid leukemia (AML) in children with Down syndrome. Morphological diagnosis of this disease could be complicated, thus flow cytometry plays a crucial role in the diagnostics of AMKL. The aim of the present study was to investigate the immunophenotypic characteristics of AMKL in children. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology. The study group included 103 patients with AMKL. Antigen expression profile was assessed by multicolor flow cytometry. We identified three groups of patients according to different levels of CD45 expression, and in majority of patients (74%) high level of CD45 expression was detected. Significant immunophenotypic differences between these groups were found. In 56% of patients trisomy of 21 chromosome was detected. Among these patients, 86% belonged to group of high CD45 expression. Moreover, children with trisomy 21 represented the majority in the group with high level of CD45 expression (64%). Also, there were found several significant differences between patients with and without trisomy 21 within the group of high CD45 expression. This study demonstrated the wide immunophenotypic heterogeneity of AMKL. In general, the revealed diversity obviously reflects the biological heterogeneity of this AML subtype.

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