[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). Incidence of transformation in the acceleration phase and blast crisis was low both in untreated and pretreated patients (1.6 and 11%, respectively) and correlated with the rate of a complete cytogenetic response (CCR). Untreated patients had no factors affecting treatment efficacy negatively, CCR probability was 96%. Blastemia, thrombocytosis and splenomegaly reduced CCR probability significantly in pretreated patients. Slow reduction of the tumor mass, late achievement of a complete hematological response and a cytogenetic response decreased probability of CCR. CONCLUSION: Glivek is a drug of choice for patients with chronic-phase CML. High probability of CCR both in untreated and pretreated patients lowers the risk of the disease transformation into the phase of acceleration/blast crisis and raises overall survival in both groups.

[The effect of the secretory products of mononuclear phagocytes from patients in a control group and from patients suffering from acute nonlymphoblastic leukemias on the cells of the U-937 monoblastic line]. / Vliianie sekretornykh produktov mononuklearnykh fagotsitov patsientov kontrol'noi gruppy i stradaiushchikh ostrymi nelimfoblastnymi leikozami patsientov na kletki monoblastnoi linii U-937.

Effects of AML and normal mononuclear phagocyte conditioned media (CM) on the proliferation and differentiation of monoblastic human cell line U-937 have been studied. The normal mononuclear phagocyte CM inhibited proliferation and weakly stimulated differentiation of U-937 cells, whereas AML CM exerted no effect. Activation of both normal and AML macrophages with phorbol ether (TPA) was followed by enhancement of CM effect. TPA treatment corrected defects of secretory activity of AML mononuclear phagocytes. A possible role of different monokines in the regulation of proliferation and differentiation of leukaemic cells is discussed.

[The use of interferon-alfa (reaferon) in patients with chronic myeloleukemia]. / Primenenie interferona-al'fa (reaferona) u bol'nykh khronicheskim mieloleikozom.

Data on long-term interferon-alpha (reaferon) therapy in 6 patients with CML (5 in chronic phase, 1 in acceleration phase) are presented. Clinicohematological remission was achieved in all the patients in a chronic phase irrespective of their group of risk. Cytogenetic improvement occurred only in one patient from a low-risk group. Reaferon had no effect in the patient in the acceleration phase. Tumor necrosis factor neither influenced viability of mononuclear bone marrow cells of patients before treatment nor suppressed proliferation. Dose independent reduction of cell viability was revealed in a patient in remission after reaferon therapy. There were no cases of apoptosis induction. Mechanisms of CML pathogenesis and interferon action in CML chronic phase are discussed.

[Effect of phorbol ester on the proliferation and differentiation of blast cells from leukemia patients and blast secretion of biologically active products]. / Vliianie forbolovogo éfira na proliferatsiiu i differentsirovku blastnykh kletok bol'nykh leikozami i sekretsiiu blastami biologicheski aktivnykh produktov.

The influence of tetra phorbol diesther (TPA) on primary blast cells of patients with acute leukemia and blastic crises of chronic myelogenous leukemia and the influence of the condition medium (CM) of the primary and TPA-treated blast cells on the proliferation of HL-60 cell line has been studied. The level of interferon-alpha (IFN-alpha) in CM was tested. TPA inhibited proliferation and induced macrophage-like differentiation of primary AML blast cells and these changes were accompanied by modulation of IFN-alpha expression in CM. The effect of blast CM on proliferation of HL-60 was both inhibitory and stimulating and depended on the time of treatment and individual characteristics of patients. It has been shown that the level of IFN-alpha in CM was not correlated with antiproliferative effect of CM. The role of individual differences in capability of primary blast cells to be induced by differentiated agents and the nature of these differences are discussed.

[Regulation of fibroblast-like cell proliferation in human bone marrow]. / Reguliatsiia proliferatsii fibroblastopodobnykh kletok kostnogo mozga cheloveka.

The influence of growth factors (GF) and some other biological active molecules on the human bone marrow fibroblast (HBMF) proliferation was studied in the monolayer system. The proliferation of HBMF, like other connective tissue cells, was serum- and GF-dependent. GF tested (EGF, FGF, insulin) produced both positive and negative effects on HBMF proliferation. It was also shown that phorbol ester, which activates protein kinase C, usually inhibited HBMF proliferation. It has been proposed that this feature of HBMF is the cause of GF bifunctional action. It has been suggested that the ability of GF to inhibit HBMF proliferation in some cases permits one to maintain cellular homeostasis in GF rich human bone marrow. HBMF of different hematological patients were characterized by individual differences in GF sensitivity. This may be secondary to the bone marrow cellular composition. For example, HBMF obtained from the bone marrow rich in total cells or megakaryocytes were more responsive to proliferation stimulating effect of GF.