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Aim: To analyze the results of treatment in patients with acute myeloid leukemia (AML) within protocols AML-17 and modified AML-17 (mOML-17) as part of two consecutive pilot studies in order to develop the best treatment strategy for AML patients aged below 60 years., Materials and Methods: The study included 89 AML patients who were aged below 60 years and received treatment within the AML-17 and mOML-17 protocols. Cytogenetic and molecular genetic studies were performed in all patients. The presence of mutations in the FLT3, NPM1, CEBPa genes was assessed by fragment analysis. 35 patients underwent a study for mutTP53, mutRUNX1 using next generation sequencing (NGS). The minimum residual population of tumor cells was evaluated by multicolor flow cytometry. Statistical analysis was performed using the procedures of the SAS 9.3 package., Results: Complete remission (CR) was achieved in 89.7% of patients treated with intensive chemotherapy (CT) courses and in 52.4% of patients treated with low-dose CT courses. 8.8% of intensively treated patients were refractory to therapy, and 38% did not respond to low-dose exposure. The early mortality rate was 3%. The overall survival and disease-free 3-year survival for patients included in 2 consecutive studies was were 60% and 67%, respectively. The level of minimal residual disease (MRD) after the first course of induction CT was an important prognostic indicator. The three-year relapse-free survival for patients in whom CR was achieved after the first course of induction CT and in whom MRD was not detected (MRD-negative status was obtained) was 90% compared to 43% for patients who were MRD positive after the first course of induction CT (p=0.00001)., Conclusion: The key factor that significantly affects the long-term results of therapy is the rate of MRD after the first course of induction CT.

Aim: To characterize the genotype and genotype-phenotype correlations in patients with Gaucher disease (GD) in the Russian Federation., Materials and Methods: One hundred adult patients with GD type 1 were examined. Their clinical study encompassed the evaluation of the severity of osteoarticular lesions from instrumental findings. An allele-specific real-time polymerase chain reaction assay was used to screen four most common acid beta-glucoside gene (GBA) mutations (N370S, 84GG, L444P, IVS2+1)., Results: The N370S mutation and the N370S/? genotype where the second allele was presented with the mutation outside the 4 most common GBA gene mutations were found in the Russian patients with GD. Analysis of the clinical manifestations of the disease revealed no association between the genotype under examination and the severity of osteoarticular lesions and supported the unfavorable role of splenectomy (SE) in the development of severe bony disease., Conclusion: SE should be carried out in patients with unclear cytopenia and splenomegaly after the diagnosis of GD is excluded. The GD patients undergoing SE should receive emergency enzyme replacement therapy to prevent severe osteoarticular lesions and an irreversible orthopedic defect.

Aim: To perform a dynamic study of beta-endorphin, hypoxia-inducible factor-1alpha (HIF-1alpha), and cytokines in hematologic patients., Subjects and Methods: Fifty-nine patients with different types of acute leukemia (AL), 30 with anaplastic anemia (AA), 24 with thrombocytopenic purpura, and 20 healthy volunteers were examined during their 40-day stay at 3200 m above sea level. beta-Endorphin and HIF-la were measured by a sandwich-type enzyme immunoassay using the Abcam antibodies. Cytokines (interleukin (IL)-2, IL-6, and tumor necrosis factor-alpha) were estimated by enzyme immunoassay applying the Pro Con kits (Saint Petersburg)., Results: Serum beta-endorphin concentrations were 1.5-2-fold above the normal values in the majority of patients with AL. The patients with initial leukocytosis at onset of disease were noted to have elevated white blood cell beta-endorphin concentrations up to 85.9 +/- 22.4 pg/ml; moreover, during chemotherapy this index increased about two times (170.74 +/- 33.8 pg/ml). There was a direct correlation between the concentrations of beta-endorphin and HIF-1alpha (r = 0.9) and an inverse correlation between the levels of IL-6 and beta-endorphin (r = -0.7). On ascending to 3200 m, under the conditions of hypoxic hypoxia the patients with AA or idiopathic thrombocytopenic purpura showed a considerable increase in serum beta-endorphin concentrations, mainly in the acute period of being at high altitudes., Conclusion: Stress factors (tumor, use of cytostatics, pain, anemia, hypoxia, high environment temperature) stimulate the elaboration of beta-endorphin, particularly in the white blood cells of patients with AL during chemotherapy. The highest elevation in the index was seen during acute adaptation to hypoxic hypoxia.

The article demonstrates objective difficulties and subjective mistakes in assessment of a clinical picture in a patient with subleukemic myelosis and thrombosis of the portal system. A careful examination of such patients is necessary to reveal latent disorders (in this case--a complete selective IgA deficiency) influencing treatment policy.

Aim: Clinical practice with the drug glivek (imatinibe mesilate, ST1571) blocking activity of oncoprotein p210 shows that a cytogenetic response can be reached in 50-60% of patients with chronic myeloid leukemia (CML), in a late chronic phase (CP) in resistance to or intolerance of interferon alpha (IF-alpha) and in 24-43% of patients in the acceleration phase (AP). This study aimed at assessment of the rate and stability of a cytogenetic response (CR) and long-term results of survival in CML patients on glivek., Material and Methods: Glivek was given to 195 CML patients (median of the treatment duration was 42 months, 1-156 months, of the patients' age--46 years). 79 patients were in CP, 116--in AP. The doses were 400 mg/day and 116 mg/day, respectively. Karyotype was studied before the treatment and later after each 6 months., Results: A considerable CR was achieved in 57% patients in CP and 44%--in AP. Of them complete CR was obtained in 48 and 35%, respectively. Marked CR is a favourable prognostic factor. Survival of patients with marked CR in CP (97% 0 and AP (89%) was significantly higher than without CR (58 and 47%, respectively, p < 0.05). Marked CR persisted in 95% cases in both phases of CML. In complete CR, a repeated study of karyotype revealed residual number of Ph+ cells both in CP and AP in 86% patients. This demonstrates necessity to take glivek continuously in achievement of a complete CR by karyotypic test. Glivek inhibits the disease progression, lowers annual lethality. 42-month (median of glivek treatment duration) overall survival reached 91 and 59% in CP and AP, respectively., Conclusion: CR is an integral index prognosticating CML course. Survival rose significantly in patients with marked CR both in CP and AP of CML. Marked CR is persistent in continuous glivek therapy. The rate of a CR depends much on the disease stage.

Aim: To characterize clinical, diagnostic and therapeutic syndromes of copper overloading in patients with hepatic lesion in combination with hemopoietic disorder., Material and Methods: Treatment results and diagnostic findings are presented for patients with clinical picture of liver cirrhosis, cytopenia and copper overloading. The examination included standard clinical and specific tests, morphological investigation of the bone marrow, copper metabolism in dynamics., Results: A case of a patient is reported in whom Wilson's disease presented in debut with a picture of decompensated liver cirrhosis and immune thrombocytopania complicated by recurrent hemorrhagic syndrome. D-penicillomine treatment initiated ex juvantibus allowed verification of the diagnosis of Wilson's disease and achievement of marked clinical response. In another case laboratory signs of copper overloading were revealed in a patient with liver cirrhosis of viral etiology (HBsAg+) and deep cytopenia associated with uneffective hemopoiesis. Chelator therapy with D-penicillamine regressed cytopenic syndrome and improved functional capacity of the liver., Conclusion: Primary or secondary nature of copper overloading in patients with hepatic cirrhosis and critical cytopenia, pathogenesis of cytopenic syndrome, practical significance of copper hemochromatoses diagnosis are discussed.

Aim: To analyse results of treatment of invasive aspergillesis in immunocompromised patients for 2000-2002., Material and Methods: The study was made of patients who, when treated with antibiotics, exhibited foci in the lungs typical for invasive aspergillesis. Aspergillas were detected in the sputum, bronchoalveolar lavage, bronchial wash-ups, aspergilla antigen (galactomannan) was detected in the blood., Results: Invasive aspergillesis was diagnosed in 25 patients. 13 (52%) patients were treated with adjuvant glucocorticoids. 19 (76%) patients had neutropenia. All the patients had fever. Foci in the lungs were in 24 patients. Aspergillas were detected in 15 patients, a positive antigen galactomannan in 7 patients. A. Fumigatus, A flavus, A. Niger occurred in 67, 26.5 and 6.5% patients, respectively. All the patients received amphotericin B (median of the treatment reached 38 days, total dose 880-3500 mg). In 5 patients amphotericin B was replaced for liposomal amphotericin B because of high creatinine. 7 patients continued with itraconasol in a dose 400-600 mg/day. The foci were removed in 3 patients. The cure was achieved in 12 patients, 13 patients, 13 patients died (cause of death--respiratory insufficiency)., Conclusion: Lethality in invasive aspergillesis in immunocompromised patients remains high--52%. Cultural detection of mycelial fungi was, as a rule, delayed. Early diagnosis of the disease requires monitoring of the aspergilla antigen in the blood and computer tomography of the chest especially in fever persisting in the treatment of wide-spectrum antibiotics.

Aim: To examine hemopoiesis and to estimate proinflammatory cytokines in blood serum from 42 patients with chronic viral hepatitis (CVH) associated with 1-3 lineage cytopenia in the blood., Material and Methods: 42 patients with diagnostically complicated hematological picture suggestive of hemoblastosis were examined using standard tests, bone marrow puncture and trepanobiopsy, laparoscopy with biopsy of the liver and spleen, transcutaneous puncture biopsy of the liver under ultrasonic control, explorative laparotomy with splenectomy and liver biopsy and, on demand, laboratory tests for hemolysis, presence of antithrombocytic and antileukocytic antibodies, iron metabolism, karyological analysis of bone marrow cells was also made., Results: The majority of the patients were diagnosed to have chronic hepatitis C with low activity of hepatic inflammation and frequent (55%) absence of the diagnostic antibodies to hepatitis C virus in the serum. In 86% of cases blood cytopenia reflected uneffective hemopoiesis and in 14% of cases hemopoiesis hypoplasia was found., Conclusion: Uneffective hemopoiesis, high content of immune response cells-effectors in the bone marrow and high concentration of TNF in the serum indirectly evidence for a pathogenetic relationship of chronic HCV infection with cytopenic hematological syndromes.

Hemopoiesis and functional activity of monocytes were assessed in 30 patients with chronic myelomonocytic leukemia (CMML). Changes in haemogram in CMML are characterized by anemia, thrombocytopenia, normal or increased count of leukocytes with absolute monocytosis and increased count of young granulocytes. Bone marrow hemopoiesis is characterized by enhanced proliferation of cellular elements of granulocytopoiesis and monocytes, suppressed erythropoiesis and megakaryocytopoiesis. Dysplastic changes are most expressed in the erythrocytic stem cells. Studies of lysosomal enzymes showed their increased activity in monocytes of CMML patients.