The efficacy of the regimens of “graft versus host” disease prophylaxis after hematopoietic stem cell transplantation from unrelated donors in children: single center experience

Graft versus host” disease (GvHD) is one of the most frequent and severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The optimal model of GvHD prophylaxis in allo-HSCT from alternative donors in children currently remains actual question. Materials and methods. The study was approved by the Independent Ethics Committee and the Scientific Council of the N.N. Blokhin National Medical Research Center of Oncology, Ministry of Healthcare of Russian Federation. Two hundred fifty six allo-HSCT were made during the period 2003–2019 from matched unrelated donors (MUD). Age median was 7.1 years old. The source of hematopoietic stem cells (HSCs) bone marrow – 76% (n = 194), peripheral blood stem cells – 24% (n = 62). GvHD prophylaxis included: tacrolimus (Tacro), cyclosporin A (CsA), methotrexate (Mtx), mycophenolate mofetil (MMF), in following combinations Tacro/Mtx (n = 98), Tacro/MMF (n = 102), tacro/Mtx + MMF (n = 3), CsA/Mtx (n = 24), CsA/Mtx + MMF (n = 12), CsA + MMF (n = 14). Median follow-up 8.9 years. GvHD prophylaxis regimen did not affect significantly the toxicity of therapy (toxicity: severe mucositis grade III–IV, nephrotoxicity, hepatotoxicity) (p = 0.4; p = 0.24; p = 0.62 respectively). In our study the rate of the overall survival (ОS) has significant differences in depending of the source of prevention GvHD. The using a combination of tacrolimus and cyclosporine with low doses of methotrexate had a positive effect on OS (p = 0.035) in patients of common non-malignant and malignant groups, as well as on the level of 2-year relapse-free survival in the group of children with malignant disorders (p = 0.671). In the general group the OS the worst results were achieved when MMF was included in the prophylaxis model. In this experience of treating of a large cohort of patients the choice of calcineurin inhibitors and methotrexate as the agent GvHD prophylaxis showed the efficacy and safety for non-manipulated MUD for both malignant and non-malignant diseases in children.