Vol 17, No 2 (2018)

Viral infections are frequent complications in the recipients of the HSCT with TCRαβ and CD19-graft depletion. Adoptive transfer of memory T cells may improve immune response to common pathogens. The work reflects the retrospective safety analysis of using the infusions of CD45RA-depleted donor lymphocytes. Data from 80 patients were analyzed. Up to 3 doses of donor lymphocytes were administered at monthly intervals, escalating to 100 × 103/kg in haploidentical transplants and 300 × 103/kg in MUD transplants. Median follow-up for alive patients was 18 (8–44) months. We did not observe any allergic reactions, septic complications after infusion of donor lymphocytes (DLI). The cumulative incidence of a de novo acute GVHD after DLI was 5% (95% CI: 2–13). In 64% patients (n = 51) was detected CMV in the blood. There were no cases of resistant CMV disease on the background of drug therapy. In patients who received DLI, 70% (n = 56) had documented appearance of virus-specific lymphocytes in peripheral blood (Elispot assay). Thus, the introduction of memory T cells at a dose of 25–100 × 103/kg body weight of the recipient for CD3+ in the case of HSCT from a haploidentical donor and 100–300 × 103/kg for an unrelated HSCT. Infusions of low dose memory T-lymphocytes after transplant engraftment are safe, potentially effective and constitute a simple measure to prevent infections in the setting of alpha/beta T-cell-depleted transplantation.

Relapse, graft-versus-host disease (GvHD) and GvHD-associated mortality are major obstacles to success of transplantation from allogenic donors in children with hematologic malignancies. Negative depletion of αβ (+) T-cells and CD19+ B lymphocytes, which permits to maintain mature donor-derived natural killer cells and γδ(+) T cells in the graft may improve GvHD control, but decrease GVL (graft versus leukemia) effect. Additional attempts at relapse prevention may be posttransplant use of hypomethylating agents. In this article, we report the results of a pilot study of decitabine safety in children with hematologic malignancies after allogeneic HSCT in our center. A total of 63 pediatric patients with hematologic malignancies underwent allogeneic HSCT between May 2012 and November 2013 enrolled in this study. Group «Decitabine+» consisted of 33 patients (14 – AML, 12 – ALL, 6 – UMML), group «Decitabine-» 31 patients (12 – AML, 17 – ALL, 2 – UMML). Decitabine was used in low dose 10 mg/m2/day during 5 days. 32 patients recieved 133 courses with median number of courses 4 (2–6). Hematologic toxicity included grade IV neutropenia in 35%, grade III in 33%, grade II in 19%; grade IV thrombocytopenia in 7,6%, grade III in 7%, infections complicated in 33%. In group «Decitabine+» 11 of the 32 patients experienced disease relapse, (mean of time to relapse 1 year), in group «Decitabine-» 9 patients (mean of time 0,42 y), p = 0,13. Decitabine can be administered to children on outpatient basis post-transplant with mostly moderate hematologic and mild visceral toxicity. Efficacy of post-transplant decitabine can be safely evaluated in a prospective controlled trial.

The article deals with the specific features of skin changes due to the chronical «graft-versus-host disease» (GVHD) reaction and practice of its drug-free modalities. This study involved 34 patients with skin manifestations of cGVHD, that were on the standard immunosuppressive therapy or extracorporeal photopheresis. The patients received non-invasive diagnostics of skin (high frequency ultrasound of skin, photodermatoscopy, sebumetry, corneometry), and also had their skin manifestations corrected with heteropolysaccharide. The outcome of the conducted study shows that rational topographical use of heteropolysaccharide on treatment of standard immunosuppressive therapy or extracorporeal photopheresis results in the recovery of epidermal barrier, bringing relief to personal discomfort as regressing the feeling of skin tightness and pruriency, fractional reduction of rash, which is confirmed by the data of the noninvasive methods of skin treatment. The noninvasive methods of valuating multifunctional skin health (high frequency ultrasound of skin, photodermatoscopy, sebumetry, corneometry) are applicable for case follow-up of patients with skin manifestations of сGVHD.

Lung metastases in patients with neuroblastoma (NB) are an extremely rare situation. Such patients have a worse prognosis and more aggressive clinical behavior of the underlying disease. This article presents an analysis of the epidemiological, clinical, radiologic features and prognosis of the disease in a group of patients with stage 4 NB and lung metastases. The cohort of NB patients with stage 4 according to the International Neuroblastoma Staging System (INSS) treated in NRC PHOI named after Dmitry Rogachev for the period 01.2012–12.2016 (60 months) was included in the analysis. Patients were stratified and treated according to the modified protocol NB-2004. Comparative analysis of patients with high-risk NB with and without lung metastases was done. Estimated event-free and overall survival were determined using Kaplan–Meier methods. Among 132 patients with stage 4 NB lung metastases were detected in 10 cases, which represented 7.5% of the whole group. The median age of the patients with lung metastases was 26.4 months (range 4.3–92.5). 9 (90%) patients were stratified to highrisk group, 1 (10%) to intermediate risk group. Comparative analysis of patients with stage 4 high-risk NB with and without lung metastases showed no statistical difference in comparison by sex, age, localization of the primary tumor, MYCN status, and the number of metastatic compartments. Progression during induction therapy was more frequent in patients with lung metastases (p = 0.02). 2-year overall survival (OS) in the group of patients with lung metastases was lower than in group without metastases to the lung (50.0 ± 15.8% vs 75.9 ± 3.9%, p = 0.045). In our study, the presence of lung metastases was more common than was described elsewhere and is clinically important because it portends a poor prognosis.

This is a clinical case of bullous epidermolysis, occurred after hematopoietic stem cells transplantation in a patient at high-risk of graft versus host disease. Given the dynamics of disease development, absence of target-organs lesions and specific response to immunosuppressive therapy, we are assuming involvement of additional etiologic factor in the skin damage pathogenesis.

IgG4-related disease is an extremely rare disorder, сcharacterized by the inflammatory infiltration of various organs, with predominance of IgG4-positive plasma cells, fibrosis and high IgG4 plasma concentration. Treatment regiments have not been optimized, especially in children. Here we discuss a case of IgG4-related disease of the orbit in a 13 year old boy and our new treatment approach involving JAK-kinase inhibitor ruxolitininb. The article also presents analysis of the state of the problem of IgG4-related disease it he world, including terminology, historical references, pathogenesis, diagnostic problems  and clinical manifestations.

Chronic GVHD remains a serious complication of allogeneic HSCT, leading to impairment of numerous organs and systems. It is characterised by the combination of auto- and alloimmune dysregulation, immunodeficiency and low quality of life. The incidence of chronic GVHD in allogeneic HSCT setting is 30–70% in adults and 15–40% in children. The problems of diagnostic and treatment of chronic GVHD are associated with poor measuring and scoring validation system. This literature review describes modern insights in chronic GVHD pathophysiology, international diagnosing criteria and new treatment approaches.