This lecture presents a series of rare clinical cases in the field of pediatric head and neck oncology. Lecture showing the importance of early diagnosing and prevention of these diseases. A series of author’s unique cases are presented. These cases show the importance of multidisciplinary approach for treatment of this category of patients.

An opinion on alpha/beta-T-cells depletion as effective platform for haploidentical hematopoietic stem cells transplantation (HSCT) is presented in this article. Historical aspects of the method development and improvement, advantages of this type of depletion in the modern era are presented. Effectiveness of alpha/beta-T-cell depletion for significant reduction of the risk of graft-versus-host disease and infection complications is showed. Article presented in the format of personal opinion of the head of department of the Dmitry Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology.

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is one of the effective methods of treatment of patients with malignant disorders of hematopoietic system. Because of absence of related and unrelated donors at the majority of Russian patients, search for alternative grafts for allo-HSCT is actual now. HSCT from partially HLA-matched related (haploidentical, haplo-HSCT) is the fast and universal method of treatment. Fifty six children and young adults 1–21 years old (age median – 9 years old) with resistant forms of acute lymphoblastic leukemia (ALL) (n = 32) and acute myeloid leukemia (AML) (n = 24) were transplanted with haploidentical donor from December 2007 to June 2013. In preparative therapy and graft-versus-host disease (GvHD) prevention the following regimens were used: myeloablative conditioning regimen (MAC) + Antithymocyte Immunoglobulin (ATGAM) (n = 20), MAC + Cyclophosphamide (CpH) (n = 5), reduce-intensity regimen (RIC) +
ATGAM (n = 14), RIC + Alemtuzumab (n = 4), RIC + CpH (n = 13). All patients received base immunosuppressive therapy with Tacrolimus and Cyclosporin A. The following types of haplo-transplants were used: combination of stimulated with G-CSG unmanipulated bone marrow (BM) and peripheral blood stem cells (PBSC) with positive CD34+ selection (n = 23) or stimulated with G-GSF unmanipulated BM (n = 33). Overall survival (OS) in this group of patients was 33.3 %. Statistically better OS (р = 0.03) was revealed in a group of patients transplanted with G-CSF stimulated unmanipulated BM – 45.5 % versus 13 % in case of combined transplant. Other factors influenced on the results of haplo-HSCT (age, status at the moment of HSCT, conditioning regimen, posttransplant therapy, engraftment, cells dose) are described in the article.

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.

Background. Hurler syndrome is the most severe type of mucopolysaccharidosis with central nervous system, cardio-vascular system and musculoskeletal system involvement. A unique method of radical therapy is allogenic stem cell transplantation (allo-HSCT). A question on high toxicity of HSCT is still unsolved for these patients.

Aim – to estimate effectiveness and toxicity of conditioning regimen with reduce intensity in patients with Hurler syndrome.

Materials and methods. Eight patients were enrolled to the investigation. Follow-up median was 20 (1–60) months. 6 patients received allo-HSCT from full HLA-matched unrelated donors, 2 patients received HSCT from partially HLA-matched unrelated donors with mismatch in A locus. The following conditioning regimens with reduce intensity were used as preparative therapy: Fludarabine – 150 mg/m2, Melphalan – 140 mg/m2, Antithymocyte Immunoglobulin (ATGAM) – 60 mg/kg. For graft-versus-host disease (GvHD) prevention Cyclosporine A in dose 1.5 mg/kg2 time per day with a combination with Methotrexate (10 mg/m2 in days +1, +3, +6) or Mycophenolate mofetil (MMF) (15 mg/kg 2 times per day during 30 days) was used. The most common transplant source were peripheral blood stem cells (PBSC) – 6 (75 %) patients, in 2 cases bone marrow was used. Due to high level of T-cells in PBSC at 3 patients, the immunomagnetic CD3/CD19-depletion or CD34+-cells depletion with the help CliniMACs device was performed. The following transplantation of CD3/CD19+-cells in dose 1.0 × 107/ kg
of recipients weight in case of full-matched unrelated donor or 1.0 × 106/ kg of recipients weight in case of mismatched unrelated donor was performed.

Results. Six patients are alive on a moment of analysis (median follow-up 20 (1–60) months). Overall survival of patients with Hurler syndrome after allo-HSCT is 75 %. All patients engrafted with complete donors chimerism on day +30. Alpha-L-iduronidase activity in leukocytes achieved normal level (average 61.3 nM/mg/18 h) on day +30. Activity was normal till day +100 – 77.6 nM/mg/18 h (normal indicator –61.0–175.5 nM/mg/18 h). Mixed donor’s chimerism was revealed on days +60 and +180 at two patients. No incidence of severe mucosytis III–IV gr. revealed. Two patients died due to transplant related causes. Causes of deaths: 1st patient – acute intestinal GvHD IV gr., III gr. skin GvHD, II gr. liver GvHD on day +69 from allo-HSCT, 2nd patient – TRALI-syndrome after packed red cells transfusion on day +45after allo-HSCT.

Conclusion. Allo-HSCT with reduced intensity conditioning regimen for the patients with Hurler syndrome is effective method of treatment without severe toxic complication. Immunoadoptive therapy can be used for rejection prevention in case of mixed donor’s chimerism.

The experience of transplant of solid organs after the hematopoietic stem cell transplantation in case of graft-versus-host disease is very moderate now. The first Russian experience of the treatment of the patient with this pathology is presented in this article. Presented follow-up results show good opportunity of liver transplant in case of treatment of severe irreversible liver defeats after hematopoietic stem cell transplantation.

Experience of non-profit organization “Hospital clowns” is presented in this article. “Hospital clowns” first in Russian Federation applied method of psychological help for patients with severe disease in a form of hospital clowns visits. The work of hospital clowns for supporting of patients during the period of intensive treatment is presented in this article. “Hospital clowns” in this case is a part of the team, that helping the patients to feel comfortable in case of entering the clinic. Short characteristic of clown’s preparation to work, theirs professional growth and improvement are showed in article. International collaboration are also presented as the one the general ways to improve and to help physicians in theirs work - treating children. What is the difference between “redheaded” and “white” clowns? How long will it takes to train a hospital clown? Which institutions is covered by “Hospital clowns”?
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Germ-cell tumors are rare, but aggressive tumors in children. The introduction of modern treatment protocols has significantly improved survival in this group of patients. This paper presents the analysis of clinical case of disseminated ovarian dysgerminoma successfully treated using multimodal therapeutic approach. The epidemiology of ovarian dysgerminoma among pediatric patients and the pathogenesis of the disease are discussed based on the analysis of the literature data. We also discuss the basic principles of diagnosis and choice of tactics of treatment.