The first successful experience effective target therapy has been achieved at imatinib administration in chronic myeloid leukemia (CML) treatment. Disease early considered practically incurable, now successful controlled using little toxic conservative therapy. During tyrosine kinase inhibitors therapy it is possible to achieve stable hematological and cytogenetic remission at the majority of CML patients, and at same patients leukemic cells do not detected by most sensitive molecular methods. In the first part of article literature data concerning CML pathogenesis, modern phases and risk group criteria, and role of interferon alpha and hematopoietic stem cells transplantation in imatinib and other tyrosine kinase inhibitors era are discussed.

220 children with acute lymphoblastic leukemia (ALL) treated according to ALL-MB-2002 protocol are included in the study. Minimal residual disease (MRD) estimated in bone marrow by three-color flow cytometry on day 15 (n=99), day 36 (n=107) and before the maintenance therapy (n=60). Day 36 positive MRD level (≥0.01%) as one of unfavorable factors statistically significant worsening of relapse-free survival was revealed (log-rank test; р<0.05). In multifactorial analysis (Cox regression) it is revealed that positive MRD level on day 36 of treatment is the strongest and independent prognostic factor influencing relapse probability (hazard ratio 6.6; p=0.031). Necessity of additional patients' stratification introduction according to MRD level after induction is proved.

Hodgkin lymphoma differs from anaplastic largecell lymphoma (ALCL) (≪Hodgkin-like≫ variant) by more frequent early stage diseases revealing (46%), mediastinal lymph nodes involvement (69%), softtissue components absence, small number of cases with more than one extranodal organ involvement (15%), ALK-protein absence (100%) and tumor cell B-immunophenotype (PAX 5+). Morphological features: the expressed pironinophilia in tumor cells cytoplasm by Broshe staining in systemic ALCL (T-/0 phenotype), that is rare observed in Hodgkin lymphoma; large tumor cells in systemic ALCL (_-/0 phenotype) have more polymorphic nucleuses with small nucleoluses in comparison with more spherical cells with large nucleoluses in Hodgkin lymphona; intrasinus growth observed almost in a half of cases in systemic ALCL (T-/0 phenotype) does not revealed in Hodgkin lymphoma; tumor tissue fibrosis is a rare observation in systemic ALCL (T-/0 phenotype), while fibrosis and capsule sclerosis are frequent morphological signs in Hodgkin lymphoma.

Dacogen treatment results of 8 MDS patients and 2 CMML patients (a course dose — 100 mg/m2) are presented. Hematological response according to modified IWG criteria (complete remission - 2 pts, bone marrow remission — 1 pts, disease stabilization — 4 pts) has been established in 70% of patients. Complete cytogenetic response has been achieved in one patient with secondary MDS and multiple chromosomal aberrations after 2 therapy courses. Complications because of which intercourse intervals elongated are registered in 3 patients. The obtained data demonstrated efficacy of Dacogen treatment for high risk MDS and CMML patients.

Bortezomib efficacy in I, II and subsequent therapy lines was studied at 51 multiple myeloma (MM) patients in Novosibirsk Hematological Center. The median of age was 66 years (39—87); patients have received from 4 to 12 therapy courses, totally — 363 courses. Total efficacy of the I line therapy was 80%. Complete remission has been achieved in 60% of patients. Efficacy of Bortezomib monotherapy and in combination with glucocorticoids in case of progression and refractory MM was 75,7%. Bortezomib was effective even at repeated administration to patients had receied it or other components of combined regimes earlier (total response — 46,2%). Bortezomib side effects were predicted and managed; most significant of them are gastrointestinal, hematologic, asthenia and peripheral neuropathia. Thus, bortezomib is highly effective drug, important in MM therapy as I and subsequent therapy line and result in significantly increase of overall survival.

On the basis of health state analysis of children with long-term acute lymphoblastic leukemia (ALL) remission, rehabilitatiuon courses in children with the indicated pathology are followed in rehabilitation department of sanatorium. The sanatorium-resort stage of treatment promoted restoration of various organ and system failure at these children. Quality of life of children in study group were statistically significant higher than before sanatorium treatment as a result of complex rehabilitation. Results suggest that detailed examination of children with long-term ALL remission (5 years and more) is necessary for data obtaining about problems with physical, psychological and social failure and development of rehabilitation programs aimed to improvement of children health state in the future.

Tumor-associated genes (PRAME, WT1 and XIAP) expression study is conducted in 34 patients with multiple myeloma (MM) in disease onset and after chemotherapy (VAD, 20 pts) and proteosom inhibitor therapy (10 pts). PRAME, WT1 и XIAP gene expression in bone marrow cells detected by polymerase chain reaction (PCR) method. PRAME gene expression in 62% primary patients was revealed, thus expression median was 0.3% that almost in 100 times greater than in bone marrow donors (0.0035%). WT1 gene expression in 20% patients was detected, and it was determined only in PRAMEpositive patients. At diagnosis XIAP gene expression was revealed in all MM patients, thus expression median was more 10 times greater than in the control groups (28% versus 2%). In patients with PRAME hyperexpression partial response was achieved only in 25% of cases, while in patients with low or absence of PRAME expression VAD therapy was effective in 75% of cases (р=0,06). After bortezomib treatment XIAP gene expression level was significantly decreased with complete and partial remission achievement: from 11-325% (median – 66%) to 1-123% (median – 20%). In cases of tumor resistance to bortezomib treatment XIAP expression increased from 16-127% (median – 36%) to 22-528% (median – 121%).

Severe congenital neutropenia (CN) is a heterogeneous disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts (ANC) below <0,5×10 9/L. In this review we summarize our current knowledge on pathophysiolgy of AML in CN patients.

There are two major subtypes of CN as judged by inheritance, 1) autosomal dominant trait defined by ELA2 mutations consisting 60% of patients and 2) autosomal recessive trait comprising approximately 30% of patients. CN is considered as a pre-leukemic syndrome, since after ten years of observation the cumulative incidence of acute leukemia is 21%. Acquired G-CSFR mutations are detected in approx. 80% of CN patients who developed AML. CN patients with acquired G-CSFR mutations define a group with high risk for development of leukemia.

Various conditioning regimes influence on sexual development and gonads function in children and adolescent after stem cell transplantation was studied. 45 patients were enrolled in the study: 23 patients with aplastic anemia (АА), who received non-myeloablative conditioning, and 22 patients with acute myeloid leukemia (AML) after myeloablative conditioning. Sexual development was estimated by Tanner classification, laboratory tests included gonadotropic hormones, sex steroids, antiMullerian hormone and inhibin B level detection. It has been shown that non-myeloablative conditioning does not influence sexual development in any patients. Extremely high frequency of gonads lesion in patients received myeloablative conditioning was registered: hypergonadotrophic hypogonadism in 8 from 12 girls with severe decrease of ovaries functional reserve in all patients; germinal epithelium lesion in 9 from 10 boys.

Introduction of biosimilars in clinical practice results in substantial reduction of direct medical costs. However, limited data concerning safety and tolerance of biosimilars exist, especially in children. We conducted double blind randomized trial comparing immediate tolerance of locally manufactured filgrastim (LeucostimR, “Biocad”, Russia) with original formulation (“Neupogen”, “Roche”, Switzerland) in children with various hematologic and oncologic diseases. Ten patients (4 F; 6 M) with a median age of 9.5 y (range 5—16 y) in whom G-CSF was indicated either by protocol or clinically were included into the study. All patients were scheduled to receive both formulations of G-CSF in order determined by randomization with permuted blocks. Pain was assessed with visual analog scale, ranging sensation of pain from 0 to 10 points. There were 41 injections of LeucostimR and 39 of Neupogen, and а median number of points attributed was 1.134 (0—10), and 1.661 (0—9) respectively (p=0,669). Intrapatient pain scores were quite consistent and did not differ by more than 1 point between any two injections. Other immediate toxicities were negligible or inexistent. Our study clearly demonstrates that both formulation of filgrastim are equally well tolerated.