Профилактические инфузии донорских лимфоцитов используют у пациентов с высоким риском развития рецидива заболевания после алло-ТГСК. Данные по безопасности раннего введения ИДЛ у детей крайне ограничены. В работе отражены частота клинически значимой реакции «трансплантат против хозяина» (РТПХ) и ее связь с общей и безрецидивной выживаемостью. Проанализированы 37 детей с острыми лейкозами и ЮММЛ, получивших профилактические ИДЛ в течение первых 6 месяцев после алло-ТГСК. Развитие острой/хронической РТПХ средней степени выявлено у 7 из 37 детей (19%), не отмечено тяжелых форм РТПХ. Наиболее часто диагностировали кожную форму хронической РТПХ в сочетании с поражением печени. Случаи летальности, связанные с осложнениями после ИДЛ, не были зарегистрированы. Напротив, индукция острой/хронической РТПХ улучшала показатели безрецидивной выживаемости и не влияла на общую выживаемость, p=0,04 и p=0,3 соответственно. Prophylactic donor lymphocytes infusion (DLI) is used in patients with a high risk of relapse after allo-HSCT. The data about safety of early start DLI in children are extremely limited. This study demonstrates the incidence of clinically significant graft versus host disease (GVHD) and correlation with overall and disease-free survival. We analyzed 37 children with acute leukemia and JMML, who had received prophylactic DLI within the first 6 months after HSCT. Moderate acute/chronic GVHD was diagnosed in 7/37 children (19%), nobody developed severe GVHD. The most children had chronic GVHD with involvement of skin and liver. There were no cases GVHD-related mortality. The induction of acute/chronic GVHD improved the relapse-free survival and did not influence on overall survival, p=0.04 and p=0.3, respectively.

Acute and chronic steroid-refractory graft-versus-host disease (srGVHD) is a life-threatening complication of allogeneic stem cell transplantation. There are a number of reports on case series describing efficacy of ruxolitinib in both acute and chronic srGVHD. We conducted a prospective study (NCT02997280) in 75 patients with srGVHD (32 acute, 43 chronic, 41 adults, and 34 children). Patients with chronic GVHD had severe disease in 83% of cases, and acute GVHD patients had grade III–IV disease in 66% of cases. The overall response rate (ORR) was 75% (95% CI 57–89%) in acute GVHD and 81% (95% CI 67–92%) in chronic. Overall survival was 59% (95% CI 49–74%) in acute group and 85% (95% CI 70–93%). The major risk factors for lower survival were grade III–IV gastrointestinal involvement (29% vs 93%, p = 0.0001) in acute form and high disease risk score in chronic (65% vs 90%, p = 0.038). Toxicity was predominantly hematologic with 79% and 44% of grade III–IV neutropenia in acute and chronic groups, respectively. There was no difference between adults and children in terms of ORR (p = 0.31, p = 0.35), survival (p = 0.44, p = 0.12) and toxicity (p > 0.93). The study demonstrated that ruxolitinib is an effective option in acute and chronic srGVHD and can be used both in adults and children.

Mucopolysaccharidosis type I (MPS IH; Hurler syndrome) is a hereditary storage disease caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase. Enzyme replacement therapy may extend the lifespan of affected patients by 6–12 years but the only currently available radical treatment option is allogeneic hematopoietic stem cell transplantation (allo-HSCT). Objectives: We aim to evaluate the influence of conditioning regimens of various intensities and “graft versus host” disease (GvHD) prophylaxis with anti-thymocyte globulin and post-transplant Cyclophosphamide (PTCy) on overall (OS) and event-free (EFS) survival, the incidence of GvHD, the normalization of alpha-L-iduronidase and glycosaminoglycan (GAG) levels over time as well as cardiovascular and cognitive recovery following allo-HSCT. The study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint Petersburg State Medical University. We included 28 patients with MPS IH who had received allo-HSCT at the clinic at the R.М. Gorbacheva Memorial Institute of Children Oncology, Haematology and Transplantation. The five-year OS was 89%, the EFS – 57%. The use of myeloablative conditioning regimens and allo-HSCT within 12 months of diagnosis improve EFS in affected patients. The cumulative incidence of grade II–IV acute GvHD and grade III–IV acute GvHD was 43% and 18% respectively. The use of PTCy results in a significantly lower incidence of this complication (69% vs 33%, p = 0.013). After allo-HSCT, normal alpha-L-iduronidase levels and urinary GAG excretion were achieved in cases where graft function was normal. Allo-HSCT is an effective treatment for patients with MPS IH. Myeloablative conditioning regimens are the preferred treatment modality for this group of patients but in cases of comorbidities or poor physical status at the time of allo-HSCT, conditioning regimens with reduced intensity may be opted for instead. PTCy may be used for GVHD prevention in patients with MPS IH without increasing the risk of cardiac toxicity.

Introduction. Steroid-refractory graft-versus-host disease (srGVHD) is one of the most severe and life-threatening complications of allogeneic hematopoietic stem cell transplantation. Currently, there is no standard treatment for this complication. In addition, there is no data on the pharmacoeconomics of various methods in the Russian Federation. The objective is to compare the effectiveness and cost of treatment of acute and chronic srGVHD, as well as the use of different approaches in therapy. Material and methods. We have conducted a pilot study in 12 srGVHD patients treated with ruxolitinib and in 24 patients of wellmatched historical control, who treated with etanercept for the acute srGVHD and with extracorporeal photopheresis for chronic srGVHD. Results. The 6-month therapy of acute GVHD was associated with significantly higher cost than therapy of chronic GVHD (4.138±2.672 vs 1.862±1.122 thd. rub., р=0.004). The major factors driving up the costs were bacterial infections (р=0.022), opportunistic viral infections (р<0.001), severity of GVHD at the start of a therapy (р=0.013) and GI involvement (р=0.006). There was no difference in 1-year failure-free survival in acute (50 % vs 67 %, р=0.9) and chronic GVHD (87.5 % vs 87.5 %, р=1.0) between ruxolitinib and the control group, although the overall response was faster in ruxolitinib group (100 % vs 71 %, р=0.035, when assessed at 28 days in acute and 12 weeks in chronic srGVHD). The mean 6-month overall costs in the ruxolitinib were higher compared to the control group (1534 thd. rub. higher for acute and 541 thd. rub. higher for chronic GVHD), however this might be attributed to higher number of previous lines in the ruxolitinib group. Conclusions. It is revealed that the treatment of acute srGVHD requires significantly higher economic costs than chronic srGVHD. The power of this study does not allow to draw conclusions regarding the efficacy of different methods. Further studies are required to determine the optimal therapy of srGVHD.