Results of allogeneic hematopoietic stem cell transplantation from a genoidentical sibling after high-dose treosulfan-based conditioning in children with intermediate-risk acute myeloid leukemia in first clinical and hematological remission

The value of allogeneic hematopoietic stem cell transplantation (HSCT) in first remission in children with intermediate-risk acute myeloid leukemia (AML) remains the matter of debate. We analyze the outcome of HSCT from a genoidentical sibling with high-dose treosulfan-based myeloablative conditioning and enhanced graft-versus-host disease (GVHD) prophylaxis in comparison with continuation of high-dose chemotherapy (CT). 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 of Ministry of Healthcare of the Russian Federation. A group of interest consisted of 22 HSCT recipients and a comparison group consisted of 240 patients who received high-dose CT. The conditioning regimens included treosulfan (n = 15), busulfan (n = 3), and melphalan (n = 4). The graft source was bone marrow in 12 patients and peripheral stem cells in 10 patients. GVHD prophylaxis was intensified either by including 1 or 2 additional immunosuppressive drugs or by increasing the duration of prophylaxis. The comparison group consisted of 240 patients who received 1 or 2 cycles of high-dose cytarabine- based consolidation therapy. The groups were matched for all initial characteristics. Engraftment was achieved in all 22 HSCT recipients: the median time to granulocyte recovery was day +16 (range, day +11 - day +21) and the median time to platelet recovery was day +15 (range, day +11 - day +28). The main toxicities of the conditioning regimens were mucositis in 12 (54%) patients, skin lesions in 6 (27%) patients, and an increase of alanine aminotransferase in 4 (18%) patients. There were no cases of toxicity-related mortality. Acute and chronic GVHD, requiring medical treatment developed in 15% of the patients. Four HSCT recipients relapsed between 3 months to 3 years after HSCT. In the high-dose CT group, 24 (10%) patients died of infectious complications and 79 (37%) patients developed a relapse. The cumulative incidence of relapse was 0.23 ± 0.10 and 0.44 ± 0.4 and the probability of the overall survival was 0.88 ± 0.08 and 0.83 ± 0.03 in the HSCT group and high-dose CT group, respectively (p 0.05). HSCT from a genoidentical sibling in intermediate-risk AML patients in first clinical and hematological remission is a safe and effective procedure, and tends to reduce the risk of AML relapse.