[Toxicity of different treatment protocols for acute myeloid leukemias in adults: the results of four Russian multicenter studies].

Aim: To comparatively analyze the toxicity of 4 treatment protocols in patients with acute myeloid leukemia (AML), which were used in the Russian multicenter center in 1992 to 2009.

Materials And Methods: The information obtained in 4 Russian multicenter studies conducted in 33 hematology departments of 26 cities and towns of the Russian Federation in 1992 to 2009 was analyzed. Randomization was made in 243 patients with AML (median age 38 years) in 1992-1995, 396 patients (median age 39 years) in 1995-1999, 392 patients (median age 39 years) in 2001-2006, and 137 patients (median age 40 years) in 2006-2009.

[Study of bone marrow microvessel density is one of the diagnostic approaches in patients with Ph-negative chronic myeloproliferative diseases].

Aim: To define an association of bone marrow microvessel density (MVD) with histological properties (the magnitude of fibrosis and quantification of megakaryocytes (MGKC)) in patients with Ph-negative chronic myeloproliferative diseases (CMPD).

Subjects And Methods: MVD was analyzed in 93 patients with different forms of CMPD, by estimating histological parameters. True polycythemia (TP) was present in 28 patients; 20 patients had essential thrombocythemia (ET), 36 had subleukemic myelosis, out them 6 were in a prefibrotic stage, and 9 with diagnosed post-TP (ET) myelofibrosis.

[Dasatinib treatment of imatinib-resistant and imatinib-intolerant patients with chronic myeloid leukemia in a chronic phase].

Aim: To analyse resistance to imatinib therapy, efficacy and safety of dasatinib.

Material And Methods: A total of 18 patients with chronic myeloid leukemia (CML) in a chronic stage received dasatinib for 9-30 months (median 30 months) to September 2008.

Results: Lethal outcomes during dasatinib treatment were absent.

[Trisomy of chromosome 8 in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia treated with inhibitors of BCR-ABL tyrosine kinases].

Aim: To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK).

Material And Methods: A total of 386 patients with CML (chronic phase--288, acceleration phase--77) received imatinib (400-800 mg/day). Because of resistance and/or intolerance some patients were switched to ITK II (nilotinib, dasatinib, bozutinib).

Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up.

Dasatinib is the most potent BCR-ABL inhibitor, with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Studies have demonstrated the benefits of dasatinib 70 mg twice daily in patients with accelerated-phase chronic myeloid leukemia intolerant or resistant to imatinib. A phase 3 study compared the efficacy and safety of dasatinib 140 mg once daily with the current twice-daily regimen.

Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia.

Purpose: Dasatinib is a BCR-ABL inhibitor, 325-fold more potent than imatinib against unmutated BCR-ABL in vitro. Phase II studies have demonstrated efficacy and safety with dasatinib 70 mg twice daily in chronic-phase (CP) chronic myelogenous leukemia (CML) after imatinib treatment failure. In phase I, responses occurred with once-daily administration despite only intermittent BCR-ABL inhibition.

Early and late hemopoietic precursor cells in patients with chronic myeloproliferative diseases.

We evaluated the content of early and late cobblestone area-forming cells, immediate progeny of hemopoietic stem cells, and committed precursor cells in the bone marrow and peripheral blood of patients with chronic myeloproliferative diseases and healthy donors. In patients with essential thrombocythemia, the number of late cobblestone area-forming cells in the peripheral blood decreased, while other parameters did not differ from those in healthy donors. In patients with idiopathic myelofibrosis, we found a decreased number of late and early cobblestone area-forming cells in the bone marrow and late cobblestone area-forming cells in the peripheral blood, while the count of early cobblestone area-forming cells in the peripheral blood increased.

[Hyperhomocysteinemia--one of the factors underlying thrombotic complications in patients with chronic myeloproliferative diseases].

Aim: To assess incidence of hyperhomocysteinemia (HHC) in patients with chronic myeloproliferative diseases (CMPD) and to analyse possible correlation between an elevated concentration of plasma homocystein (HC) and thrombotic complications.

Material And Methods: The trial enrolled 61 patients: 39 CMPD patients with thrombotic complications and free of them, 22 nonhematological patients with thrombosis. The control group consisted of 40 healthy donors.

[Prognosis factors in imatinib mesilate therapy in patients with a chronic phase of Ph-positive chronic myeloid leukemia: data from a multicenter non-randomized trial in Russia].

Aim: To reveal prognostically significant factors affecting efficacy of glivek therapy in untreated (duration of the disease < or = 6 months) and pretreated (duration of the disease > 6 months) patients with chronic myeloid leukemia (CML) in a chronic phase.

Material And Methods: A total of 338 patients (64 untreated and 274 pretreated) with a chronic-phase CML on glivek therapy entered the trial.

Results: Five-year survival on glivek was high (89, 98 and 88% in untreated and pretreated patients, respectively).

Application of PRV-1 mRNA expression level and JAK2V617F mutation for the differentiating between polycytemia vera and secondary erythrocytosis and assessment of treatment by interferon or hydroxyurea.

Increased PRV-1 mRNA expression and the presence of Jak2(V617F) mutation in peripheral blood granulocytes are specific markers for chronic myeloproliferative disorders (MPD), which facilitate the differential diagnosis between polycythemia vera (PV) and secondary erythrocytosis (SE) and may be helpful for monitoring treatment efficacy in MPD patients. We evaluated the presence of the Jak2V617F mutation and increased PRV-1 mRNA expression along with previously established markers - erythropoietin (EPO) independent colony formation (EEC) and erythropoietin level for diagnosis of PV and assessment of treatment efficiency. Increased PRV-1 expression was found in 37 out of 46 patients diagnosed with PV (80%), in 4 out of 15 patients diagnosed with essential thrombocythemia (ET) (27%) and in 4 out of 8 patients with chronic idiopathic myelofibrosis (CIMF) (50%), and increased PRV-1 expression plus EEC formation was observed in 19 of 36 examined MPD patients indicating the superiority of PVSG and WHO bone marrow criteria for the diagnosis of ET, PV and CIMF.

[The results of a multicenter randomized trial on the treatment of acute myeloid leukemia of adults].

Aim: Systematization of the results of 20-year multicenter randomized trial of the efficacy of treatment of acute myeloid leukemia (AML) of adults; presentation of the design of the study of the strategy of consolidation and maintenance therapy after high-dose consolidation initiated in 2007.

Material And Methods: Treatment outcomes on the protocol AML-01.01 are presented for 354 AML patients from 29 hematological centers located in 22 towns of Russia and 2 towns of Ukraine.

[Monitoring of minimal residual disease in patients with chronic myeloleukemia: clinical value of real-time polymerase chain reaction].

Aim: To quantitatively determine minimal residual disease (MRD) by real-time polymerase chain reaction (PCR) in patients with a chronic phase (CP) of chronic myeloid leukemia (CML).

Materials And Methods: A molecular response was analyzed in 53 CML CP patients with incomplete and complete cptogenetic response (ICR and CCR) during imatinib therapy (median follow-up 36 months). BCR-ABL gene type p210 expression was quantitatively determined by real-time PCR under the TaqMan technology (an ICycler IQ device).

Phase II, randomized, multicenter, comparative study of peginterferon-alpha-2a (40 kD) (Pegasys) versus interferon alpha-2a (Roferon-A) in patients with treatment-naïve, chronic-phase chronic myelogenous leukemia.

The efficacy and safety of peginterferon-alpha-2a (40 kD) (PEG-IFNalpha-2a), 450 microg once weekly, versus IFNalpha-2a, 9 MIU once daily, for 12 months, was evaluated in a Phase II study in IFN-naïve patients with chronic-phase, Philadelphia-chromosome-positive CML. At the end of the treatment, complete hematological response was observed in 66.2% (47/71) and 45.

Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial.

Therapeutic options for chronic myelogenous leukemia (CML) resistant to 400 to 600 mg imatinib are limited. Escalating imatinib doses may overcome resistance. Dasatinib, a significantly more potent inhibitor of BCR-ABL, is safe and effective in this population.

[Chronic myeloproliferative diseases and pregnancy].

Aim: To analyse the course of pregnancy in chronic myeloproliferative diseases (CMPD) with hyperthrombocytosis, primarily, essential thrombocytemia.

Material And Methods: The analysis of thrombogenic risk factors covered literature data and 8 cases observed by the authors.

Results: Six pregnant women received long-term treatment with preparations of interferon-alpha in a dose 9-20 million IU a week (both before and during pregnancy).

Defective adhesion and homing of hemopoietic precursors from the bone marrow of patients with myelodysplasia to stromal cells of normal bone marrow cultures.

Hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome were characterized by lower adhesion to normal stromal sublayer compared to bone marrow precursors from healthy donors, while adhesion to fibroblast monolayer and fibronectin was similar in bone marrow cells from patients and donors. In vitro experiments showed that the percentage of adherent hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome in normal stromal sublayer and fibroblasts was lower compared to healthy donors. The decrease in adhesive activity of hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome probably contributes to impairment of cell-cell interactions in the bone marrow of these patients.

[Invasive pulmonary aspergillesis].

Aim: To evaluate the results of therapy of invasive pulmonary aspergillesis (IPA) in one medical center from 2000 to 2005.

Material And Methods: Diagnosis of IPA was made according to the International criteria. Incidence of verified IPA was 2%, probable--84%, possible--14%.

[Cytogenetic response as a marker of efficacy of chronic myeloid leukemia therapy with a BCR-ABL thyrosine kinase inhibitor glivek].

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).

[Chromosomal aberrations in myelodysplastic syndrome].

Aim: To analyse incidence rate of chromosomal aberrations in myelodysplastic syndromes (MDS), specification of clinicomorphological features of some cytogenetic variants.

Material And Methods: Chromosomal analysis by the method of G-differential staining of chromosomes was made in 209 patients with different variants of MDS. RESULTS; Clonal chromosomal aberrations occured in 60.

[Prediction of interferon therapy efficacy in chronic myeloid leukemia according to data of histomorphological study].

Aim: To investigate factors determining prognosis and efficacy of induction therapy including interferon-alpha-2b (intron-A, Schering Plough) in patients at an early chronic stage of Ph-positive chronic myeloid leukemia (CML) as shown by histomorphological examination.

Material And Methods: The analysis covered 52 CML patients treated at an early chronic phase with intron-A in a standard daily dose 5 IU/m2 in combination with low-dose cytosinearabinoside (10 mg/m2, s.c.

[Molecular-cytogenetic monitoring of different regimens of treatment in patients with chronic myeloid leukemia].

Aim: To conduct molecular-cytogenetic monitoring of bone marrow cells in different regimens of chronic myeloid leukemia (CML) treatment.

Material And Methods: A total of 651 samples of bone marrow from 319 CML patients were studied. 229 patients received polychemotherapy and 90 patients--interferon-alpha.