T-cell acute lymphoblastic leukemia (T-ALL) is a tumor developing as a result of malignant transformation of precursor T-cells. Despite the fact that T-ALL is responsible for about 10-15% of all ALL cases in children, it is essential to separate T-ALL in a special subgroup, as a nosological entity by the tumor biology, poor clinical outcome and resistance to therapy. We analyze the results of treatment of 644 patients with T-ALL, registered in the data base of the Russian-Byelorussian Research Group over 24 years of its work. The initial characteristics of the patients, responses to therapy, prognostic factors, and efficacy of various therapeutic options are analyzed.
The paper gives information on the young and dynamic team of the pediatric oncology unit, Nizhnevartovsk District Children’s Clinical Hospital (DCCH). The 27-bed unit, headed by Guzel Rafailovna Sharapova, annually receives as many as 37 primary patients with hematological diseases and cancer. It takes an active part in the activities of DCCH and the National Society of Pediatric Hematologists and Oncologists.
One of the main risk-factors of acute lymphoblastic leukemia (ALL) is age. The most favorable age group is children from 2 to 9 years old, and the adolescents and young adults have the worst prognosis. Treatment of ALL at adolescents and young adults is a unique problem of modern hematology now. This work presents the analysis of 368 cases of patients with primary ALL 15–18 years old, which were registered in the database of Russian-Belarussian group from April 2002 to November 2014. The aim of the analysis was the estimation of effectiveness of different generations of protocol for adolescents and prognostic significance of different factors to reveal the ways of future therapy optimizing in this age group. Event-free survival of adolescents 15–18 years old according our study was 56 ± 5 % in ALL-MB-2002 study and 57 ± 6 % in ALL-MB-2008 study. We did not received any differences in survival based on immunophenotype of blast cells. But the risk group analysis showed the worst results at patients with ALL from pre-B-precursor cells of high risk. No difference was revealed according the gender. One of the general problems remains high toxicity of therapy at patients of this age group. Treatment related mortality (TRM) was 13.2 and 12 % at ALL-MB-2002 and ALL-MB-2008 accordingly. Main cause of deaths remains infection.
SHH group of medulloblastoma is a heterogeneous tumor cohort. The neoplasms differ by biological characteristics as well as clinical features and prognosis of the disease. Purpose of the study is the analysis of clinical, molecular and genetic features for prognosis defining in patients with SHH group medulloblastoma. 28 patients with SHH group medulloblastomas were included in the study. The MB molecular group verification was performed in parallel by Nanostring gene expression profiling and immunohistochemical assessment of tumor samples. The detection of TP53 gene mutations was carried out with Sanger sequencing. The prognostic impact of the clinical, molecular and genetic factors of the disease was analyzed by calculating 5-years event-free survival (EFS). The median of follow up time achieved 38.9 months. All patients harboring the TP53 mutation (n = 3) had dismal outcome (two patients died from the progression of the disease, one patient has secondary tumor). Children from older age group (> 3 years) had more adverse events comparing to younger children (< 3 years): EFS 49.2 ± 31.3% vs. 78.8 ± 13.9%. The relapse of the disease occurred in 7 patients (25%). Notably, that in younger children the second line treatment was effective. The presence of TP53 mutations as well as age above 3 years are associated with poor prognosis in SHH group medulloblastomas. The novel molecular and genetics markers are needed for precise prognosis defining.
The results of two consecutive multicenter clinical trials enrolled 241 patient with childhood mature B-cells non-Hodgkin lymphomas/leukemia are presented. Patients received treatment according B-NHL 2004mab protocol (n = 83) and B-NHL 2010M (n = 158) with combined immunochemotherapy (ICT) in Russian and Belarus pediatric clinics from 2004 to 2015 years. Primary patients with different mature B-NHL (Burkitt lymphoma/leukemia, diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma (DLBCL and PMBCL)) aged from 2 to 18 years are included in the studies. Protocol B-NHL 2004mab for treatment of children and adolescents with B-NHL/B-AL, stage III and IV, includes a combination of chemotherapy (PCT) and rituximab – an antibody against the B-cells receptor CD20. PCT courses similar to those in the B-NHL BFM90 protocol (group III) with the exception of methotrexate dose in induction courses, reduced to 1 g/m2 /24 h in order to reduce toxicity. Rituximab (Mabthera, 375 mg/m2 /h) used for the first time in the treatment of children and adolescents with B-NHL. Of the 83 patients included, clinical remission was achieved in 77 (92.8 %). With a median follow time of 51.6 months, remission continued in 23 (85.2 %) patients with B-AL, in 32 (88.9 %) patients with LB and 19 (95.0 %) patients – with DLBCL. With median follow time of 65.2 months, event-free and overall survival was 84 ± 6 and 82 ± 8 %, respectively. Based on previous experience in order to further optimize B-NHL treatment, new protocol B-NHL 2010M with effect-adapted therapy and improvement of stratification risk group criteria was proposed. Overall survival in patients of 1st and 2nd risk groups with full implementation of diagnosis and treatment is approaching 100 %. In interim analysis of 3rd risk group patients, pOS was 88 ± 3 %. The incidence of induction death (infections, metabolic complications) remains within 2.7 % (n = 4); refractory cases (n = 2; 1.3 %) and relapses (n = 4; 2.7 %) developed after 2–4 months of remission, were observed only in patients with Burkitt lymphoma/leukemia. In this cases 2nd line therapy and auto-HSCT is not allowed to achieve remission. All PMBCL and DLBCL patients were achieved remission, but in 50 % of cases only after second line, radio- and cell therapy. The authors conclude that a combined immunochemotherapy of B-NHL in children and adolescents, including the target drug (rituximab) and 5-day courses of cytostatic therapy, highly effective, despite a reduce induction intensity. Therapy for the analyzed protocol requires qualitative dynamic efficacy monitoring and timely correction of therapy. In order to solve a refractory problem and further reduce the toxicity, necessary to continue research using fundamental discoveries in recent years.
Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic malignant neoplasms, the substrate of which is the clonal proliferation of myelopoiesis progenitor cells. The key AML features are uncontrolled proliferation and arrest of cell differentiation, which leads to specific damage of various organs and systems; in the absence of specific therapy, death occurs quite quickly. Spontaneous AML remission is considered a rare phenomenon. In 1878, the first mention of AML clinical manifestations regression after acute infectious disease was made, but the remission was short and a relapse soon occurred. The article presents a literature review and 3 clinical cases, systematizing information on known cases of spontaneous AML remission in children. Attention is focused on various mechanisms that may contribute to spontaneous AML remission in children. These may be either immune-mediated reactions to leukemic cells or the influence of infectious agents, which in some cases activate antitumor immunity. In some cases, a direct correlation is observed between the presence of infectious processes and a decrease of tumor cells number, which emphasizes the importance of further studying the molecular mechanisms of interaction between immune and tumor cells. There is no evidence of a correlation between age and spontaneous remission. Spontaneous remission, although rare, may be a significant factor to consider when planning a treatment strategy. Further clinical studies are needed to better understand the spontaneous remission mechanisms in childhood AML. This may lead to improved treatment results and increased chances of a favorable outcome for patients.
To determine predictors for decision-making on a differential approach to choosing glucocorticosteroids (GCS) for children and adolescents with acute lymphoblastic leukemia (ALL).The analysis covered 1064 primary patients aged to 1 to 18 years with ALL who had been registered at the clinics of Russia and Belorussia in April 2002 to November 2006. Before induction therapy, the patients were randomized into a dexamethasone (DEXA) 6 mg/m2 group (n=539) and a methylprednisolone (MePRED) 60 mg/m2 one (n=525).The entire group showed no statistically significant differences in survival rates between the patients receiving DEXA or MePRED. However, an analysis of age groups revealed the benefits of DEXA in children younger than 14 years (the event-free survival (EFS) was 76±2 and 71±2%, respectively (p=0.048); the overall survival (OS) was 81±2 and 77±2%, respectively (p=0.046); therapy-induced mortality was 6.4% (DEXA) andl 1.1% (MePRED) (p=0.01 4); the rate of isolated extramedullary relapses was 1.5% (DEXA) and 4.4% (MePRED) (p=0.009). At the same time, EFS and OS in 14-to-18-year-old adolescents were statistically significantly higher than in those who used MePRED (EFS, 65±6 and 52±6%, respectively (p=0.087); OS, 72±6 and 61±6%, respectively; (p=0.l 7).The findings suggest that it is possible that the choice of a GCS for ALL therapy must be also based on a patient's age. There is a need for further studies of this matter in prospective randomized multicenter trials in children and adolescents.Цель исследования. Определить прогностические факторы для принятия решения о дифференцированном подходе к выбору глюкокортикостероидов (ГКС) у детей и подростков с острым лимфобластным лейкозом (ОЛЛ). Материалы и методы. В анализ включили 1064 первичных пациентов с ОЛЛ в возрасте от 1 года до 18 лет, зарегистрированных с апреля 2002 г. по ноябрь 2006 г. в клиниках России и Беларуси. Перед началом индукционной терапии пациентов рандомизировали в группу применения дексаметазона (DEXA) в дозе 6 мг/м2 (n=539) и в группу применения метилпреднизолона (MePRED) в дозе 60 мг/м2 (n=525). Результаты. В общей группе не получено статистически значимых различий по выживаемости между пациентами, получавшими DEXA и MePRED. Однако при проведении анализа в возрастных группах выявлены преимущества DEXA у детей младше 14 лет (бессобытийная выживаемость - БСВ: 76±2 и 71±2% соответственно; p=0,048; общая выживаемость - ОВ: 81±2 и 77±2% соответственно; р=0,046; летальность, обусловленная терапией: 6,4% (DEXA) и 11,1% (MePRED); р=0,014; частота изолированных экстрамедулярных рецидивов: 1,5% (DEXA) и 4,4% (MePRED); р=0,009). При этом у подростков (14-18 лет) БСВ и ОВ оказались статистичеаки значимо выше при использовании MePRED (БСВ 65±6 и 52±6% соответственно; р=0,087; ОВ 72±6 и 61±6% соответственно; р=0,17). Заключение. Полученные данные свидетельствуют, что выбор ГКС для использования в терапии ОЛЛ, возможно, должен основываться, в том числе на возрасте пациента. Необходимо дальнейшее изучение этого вопроса в проспективных рандомизированных многоцентровых исследованиях у детей и взрослых.
