Here, we report on a new treatment protocol for patients with BRAF-positive Langerhans cell histiocytosis (LCH). To achieve remission in the affected patients, we used vemurafenib (a targeted drug) in combination with cytarabine (Ara-C) and cladribine (2-CdA). The study included 27 patients: 18 children with multisystem LCH with risk organ involvement (RO+) and 9 – with multisystem LCH without risk organ involvement (RO–). The treatment started with a 28-day cycle of vemurafenib, with subsequent discontinuation. On Day 29, Аra-C + 2-СdA chemotherapy cycle № 1 was initiated. Vemurafenib treatment was again started on Day +1 after the Ara-C + 2-CdA cycle. The interval between the cycles was 28 days. Similarly, the next two Аra-C + 2-СdA chemotherapy cycles (№ 2 and № 3) were carried out. Then therapy with vemurafenib was stopped and 3 cycles of 2-CdA were administered. All the patients responded to the treatment quickly: on Day 28, disease activity score decreased from 15 to 2 in the RO+ group and from 4 to 0 in the RO– group. The two-year relapse-free survival in the RO+ group was 82 % (95 % confidence interval 66–100), and 89 % (95 % confidence interval 71–100) in the RO– patients. The overall survival in both groups was 100 %. Our study demonstrates the safety and effectiveness of the treatment with vemurafenib and intermediate-dose 2-CdA and Ara-C in children with multisystem RO+ and refractory LCH. This prospective non-randomized multicenter study was approved by the Independent Ethics Committee (Minutes No. 3e/1-18) 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. It is registered at clinicaltrials.gov under the number NCT03585686. The first patient was enrolled on 22 June 2018, the data collection was stopped on 30 April 2023.

Mutations in the MECOM gene (MDS1 and EVI1 complex locus) may be one of the causes of a rare combination of congenital radioulnar synostosis resulting in extremely limited forearm pronation and supination, and amegakaryocytic thrombocytopenia. The clinical spectrum of the disease can range from isolated radioulnar synostosis with or without hematologic manifestations to severe bone marrow failure without skeletal abnormalities. Other phenotypic manifestations include clinodactyly, brachydactyly, cardiac and renal malformations, presenile hearing loss, and B-cell deficiency. In view of the heterogeneity of phenotypic manifestations of the disease, the term “MECOM-associated syndrome” was proposed for all patients with mutations in the MECOM gene. Here we report 3 pediatric cases of MECOM-associated syndrome with different clinical manifestations, diagnostic approaches, therapeutic options, and outcomes. The patient’s parents agreed to use the information, including the child’s photo, in scientific research and publications.

Relevance. Infectious septic complications caused by polyresistant gram-negative micro-organisms are a pressing issue in the treatment of patients after polychemotherapy (PCT) and hematopoietic stem cell transplantation at the high risk of the fulminant current and high lethality against the background of hematopoesis aplasia. One of the therapeutic strategies of antimicrobial treatment is the systematic use of 0.5 % hydroxymethylquinoxaline dioxide (dioxidine) solution in the complex antibacterial therapy of patients with severe infectious-septic complications. The preparation has a bactericidal type of action, a wide spectrum of antibacterial activity. Experience in adult clinical practice has demonstrated the effectiveness of dioxidine in the treatment of the most severe forms of aerobic and anaerobic infection. Strict dose enforcement and injection technique to avoid the appearance of side effects. Data on the intravenous use of dioxin in children are presented in a limited number of scientific literature.The aim of the study was to demonstrate the efficacy of systemic use of hydroxymethylquinoxaline dioxide (0.5 % dioxidine solution) in children with infectious complications progressing against the background of aplasia of hematopoiesis caused by multidrug-resistant pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia.Materials and methods. 16 patients with a verified gram-negative infection were prescribed 0.5 % hydroxymethylquinoxaline dioxide solution as part of a combination antimicrobial therapy were included in the retrospective study. The median age of patients was 5 years (6 months – 16 years), 11 (69 %) were boys and 5 (31 %) girls.All children included in the study has infectious-septic complications at the PCT-induced hematopoietic aplasia, obtained according to the protocols of the main disease: severe combined immune deficiency (n = 2), idiopathic aplastic anaemia (n = 3), solid tumor (n = 2), acute myeloblastic leukemia (n = 7), acute lymphoblastic leukemia (n = 2). The main criterion for adding to the study was the existence at the least one site with a verified gram-negative infection (Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter cloacae, Stenotrophomonas maltophilia): bacteriemia (n = 11), oral mucosa (n = 6), ulcerative necrotic damage of perineum (n = 6), enterocolite (n = 6), infectionseptic compartments in the subcutaneous fat (n = 4), pleuropneumonia (n = 4), abscesses and inflammatory infiltration of the liver, spleen, pancreas, kidneys, lymph nodes (n = 1), infection of soft tissues in the area of the ventricular bypass with inflammatory changes of the brain membranes (n = 1).All patients received 0.5 % of the solution of dioxin by injection according of vital importance, as they had pathogens with confirmed laboratory resistance or clinical progression of the infectious process against the background of combined antibacterial therapy.Discussion. There is a complete control of fulminant developing infectious-septic processes caused by polyresistant micro-organisms against the background of hydroxymethylquinoxaline dioxide therapy in all 16 patients. The eradication of the pathogen, according to the microbiological study, has been confirmed in almost all observed patients, the efficacy of the drug has been preserved throughout the period of treatment, and the resistance of micro-organisms has not been observed. Strict adherence to the dosing and infusion technique of hydroxymethylquinoxaline dioxide has helped to achieve the full resolution of the infection process in all children without side-effects.Conclusion. On the basis of the experience presented, in immunocomputed patients of young age, 0.5 % dioxidine solution can be used as a necessary reserve preparation for the treatment of the most severe forms of infections of different localization, caused by polyresistant strains of gram-negative micro-organisms.

Background. Allogenic hematopoietic stem cell transplantation (allo-HSCT) for patients with mucopolysaccharidosis is the radical method of therapy nowadays. Myeloablative conditioning regimens allow to achieve good engraftment and do not compromise clinical status of a patient. Aim – to show effectiveness of allo-HSCT with myeloablative conditioning for patients with Hurler syndrome (HS). Patients and methods . We analyzed 23 allo-HSCT at 22 patients with HS which were performed in 2002–2015. HSCT from unrelated donors (10/10 and 9/10) were performed in 18 cases. Transplant: bone marrow – 73.9 % (n = 17); peripheral blood stem cells – 17.4 % (n = 4); cord blood (CB) – 8.7 % (n = 2). Age median – 1.86 y.o. (10 months – 3.8 years). Conditioning regimen: Busulphan/Treosulphan + Fludarabine + Thiotepa/Melphalan and Antithymocyte Immunoglobulin +/– Rituximab (in case of HSCT from unrelated donor). Results. 19 patients are alive now. 15 patients have complete donor’s chimerism now. All patients have good answer on general disease (best answer correlated with minimal interval between diagnosis and HSCT). Primary graft failure was in one case of CB transplantation. Graft rejection was diagnosed in 3 cases. Causes of death were infection complications in all cases. Results improved during last 5 years – good infection control and therapy of infection and immune complications. Median of follow-up is 48.62 (8–130) months, overall survival 83.2 %, event-free survival – 71.5 %. Conclusion. Our results suggested that allo-HSCT with myeloablative conditioning (with Melphalan inclusion) for the patients with HS is effective way of therapy to stop neurodegeneration processes. Optimization of prevention and treatment of infection complications and graftversus-host disease allows to improve significantly results of HSCT.