[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.

[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). 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.

[Determinaton of intracellular immunoglobulins by means of immunofluorescence. 1. The standardization of monospecific luminescent antisera against human G-, A- and M-class immunoglobulins in bone marrow preparations from patients with paraproteinemic hemoblastosis]. / Opredelenie vnutrikletochnykh immunoglobulinov metodom immunofliuorestsentsii. Soobshchenie 1. Standartizatsiia monospetsificheskikh liuminestsiruiushchikh antisyvorotok protiv immunoglobulinov cheloveka G-, A-, i M-klassov na preparatakh kostnogo mozga bol'nykh paraproteinemicheskimi gemoblastozami.

To assess the specificity and the activity of fluorescent antisera against human G-, A-, M-classes the authors used in the capacity of a substrate, containing specific antigen preparations, bone marrow cells of patients with paraproteinemic hemoblastosis. The method of making the preparations used permitted sufficiently objective assessment of the activity and specificity of the mentioned monospecific fluorescent conjugates. As revealed, the bone marrow preparations could be stored at -70 degrees C for over one year.

[Determination of the subclasses of monoclonal human immunoglobulins G and of the light chain type with the aid of specific antisera]. / Opredelenie subklassov monoklonal'nykh IgG cheloveka i tipa legkikh tsepeí s pomoshch'iu spetsificheskikh antisyvorotok.

Sera of 86 patients suffering from G-myeloma were studied for the purpose of determination of subclasses of monoclone IgG. Investigations were carried out by means of antisera to subclasses IgG by the double diffusion method in gel after Ouchterlony. The following distribution of myeloma Ig was revealed: G1--70%, G2--17%, G3--11%,and G4--2%. In typing of the light igG chains by the method of immunoelectrophoresis, using antisera to the light chains of immunoglobulins of the chi and lambda type it was found that IgG1 chi was encountered more frequently than IgG1 lambda (3:1 ratio). The amount of the sera with the IgG2, IgG3, and IgG4 was insufficient for the reliable conclusion of their distribution by the type of light chains.

[A modern therapeutic strategy in Ph-positive chronic myeloleukemia]. / Strategiia sovremennoi terapii Ph-pozitivnogo khronicheskogo mieloleikoza.

The aim of this paper was to show the validity of programmed treatment of chronic myeloid leukemia (CML) patients regarding the risk group. In a group of low CML risk monochemotherapy (myelosan or hydroxyurea) was applied. In a group of moderate or high CML risk cytostatic therapy was performed in two variants: as monotherapy and polychemotherapy. Of 112 patients with CML, 50 received cytostatics plus long-term course of interferon-alpha. The combined treatment was well tolerated.

[Osmotic activity of plasma in plasmapheresis in patients with multiple myeloma]. / Osmoticheskaia aktivnost' plazmy pri plazmafereze u bol'nykh mnozhestvennoi mielomoi.

AIM: To control safety and efficiency of therapeutic plasmapheresis (PA) by osmolality, colloido-osmotic pressure (COP), total protein concentration before and after the procedure in patients with paraproteinemic hemoblastosis. MATERIAL AND METHODS: 20 patients with multiple myeloma have undergone 42 PA procedures conducted by two techniques: continuous flow centrifugation on blood fractioners or intermittent centrifugation of blood in plastic containers. The removed plasma volume averaged 1/3 (group 1) or 2/3 of the plasma volume (group 2). The removed protein reached 62-197 g. Isotonic sodium chloride solution and/or reopolyglucin (20-60 g) replaced the removed plasm. Total protein concentration was measured colorimetrically in biuretic reaction, plasma osmolality--cryoscopically and COP--on Knauer osmometer. RESULTS: PA leads to a short decline in osmolality (97.0-99.1%), of total protein concentration (82.8-78.6%) and of COD (79.2% in replacement with saline and 90.2% in replacement with dextran). During recovery after the procedure plasma osmotic activity and protein concentration return to the baseline. CONCLUSION: In elimination of 1/3 of plasma volume and crystalloid infusion, hemodilution promotes release of abnormal proteins from the tissues into the circulation and thereafter removal them from the organism. In removal of 1/2 and more of plasma volume, COP demans correction made by administration of colloids, e.g. solution of low molecular dextran. There is a potential danger of COD lowering several hours after PA due to different speed of dextran elimination and mobilization of protein reserve.

[The monitoring of protein-volemic indices during plasmapheresis in patients with paraproteinemic hemoblastoses]. / Monitoring belkovo-volemicheskikh pokazatelei pri plazmafereze u bol'nykh paraproteinemicheskimi gemoblastozami.

We studied quantitative characteristics of plasma protein before, during and after 133 plasmapheresis (PA) procedures in patients with multiple myeloma and Waldenstrom's macroglobulinemia. A value of removed plasma volume (RPV) was calculated as a part plasma volume (PV) before PA with consideration of quantity and consequence of replacement solution. In the case when we removed 30% of calculated PV we replaced it only with electrolyte solutions. In the case of 50% PV removing, the replacement was a combination of low molecular weight dextran and electrolyte solutions (1:2) or 5% albumin and electrolyte solutions. The results support correlation between a level of total protein and RPV, kind of replacement solutions. We recommend two regression equations for efficient and safety planning RPV and for prediction of protein level after PA. This simple and fast method can be used for prognosis of critic PA parameters, to decrease a risk of side effects and for optimal use of albumin replacement solutions.

[Interferon alfa-2b treatment of adult patients during early chronic phase of Ph1-positive chronic myeloid leukemia (initial report on a cooperative study, protocol CML-MIG-97)]. / Terapiia bol'nykh v rannei khronicheskoi faze Ph'-polozhitel'nogo khronicheskogo mieloleikoza vzroslykh preparatami interferona-alfa-2b (pervoe soobshchenie po rezul'tatam kooperirovannogo issledovaniia po protokolu KhML MIG-97).

AIM: Evaluation of clinical effectiveness of two regimens of induction therapy of an early chronic stage of Ph'-positive chronic myeloid leukemia including interferon-alpha 2b (intron-A, "Schering Plough") in a cooperative randomised trial on the protocol CML MIG-97. MATERIALS AND METHODS: 42 patients with chronic myeloid leukemia were treated either with intron-A in standard doses (5 IU/m2/day) alone or in combination with monthly 10-day courses of low-dose cytosine-arabinoside (10 mg/m2/twice a day). The effect was assessed by the international criteria of a complete and partial hematologic remission and the cytogenetic response. RESULTS: Intron-A therapy in standard doses produced a pronounced cytogenetic response in 28.6% of the patients. In low-dose interferon-alpha-2b (reaferon and intron-A, 1-3 IU/m2/day) in combination with various regimens of chemotherapy only minimal cytogenetic response was achieved. CONCLUSION: A pronounced cytogenetic response in early chronic stage of CML to standard doses of intron A holds promise in prolongation of CML patients survival and design of new effective therapy programs.

[Prediction of interferon therapy efficacy in chronic myeloid leukemia according to data of histomorphological study]. / Prognozirovanie éffektivnosti interferonoterapii pri khronicheskom mieloleikoze po dannym gistomorfologicheskogo issledovaniia.

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. , daily for 10 days of each month). The treatment efficacy was assessed by the international criteria of complete and partial hematological remission and cytogenetic response. The cytogenetic study employed the direct method, even and G-differential staining, fluorescent hybridization in situ (FISH). The sections were stained with hematoxilin-eosine by Gomori, van Gieson. Histological samples were examined with histomorphometry. Immunohistochemical examination was made on paraffin sections using a panel of monoclonal antibodies CD3, CD4, CD8, CD20, NK, PCNA, Ki-67 (Dako, Denmark). RESULTS: Repeated assessment of histomorphological parameters such as erythroid lineage, degree of myelofibrosis and reduction of leukemic population indicate the treatment efficacy. Estimation of the level of leukemic population proliferation in trephine biopsies from CML patients with monoclonal antibodies PCNA and Ki-67 before the treatment is prognostically significant as it further correlates with the cytogenetic response (r = 0.821, p = 0.000000). CONCLUSION: It is valid to study histomorphological picture of CML to prognosticate and assess treatment efficacy with standard doses of interferon-alpha with high probability.

[Dynamics of clinico-immunologic indices in patients with endocrine ophthalmopathy undergoing treatment with the preparation parlodel]. / Dinamika kliniko-immunologicheskikh pokazatelei u bol'nykh s éndokrinnoi oftal'mopatiei pri lechenii preparatom parlodel.

The immune status and the time course of ophthalmological indices were studied in 54 patients with endocrine ophthalmopathy during bromocriptine therapy. Twelve weeks after the onset of therapy indices of the immune status returned to normal in parallel with the regression of ophthalmological symptoms. In the control group (20 patients with endocrine ophthalmopathy who did not receive bromocriptine) significant improvement of the clinicoimmunological status was unnoticed. An increase in the number of T-lymphocytes, a decrease in the number of B-lymphocytes, an increase in the level of IgG, and a decrease in the levels of IgA and IgM were observed during bromocriptine therapy. The time of the immunity indices could serve as a criterion of bromocriptine therapeutic efficacy in patients with endocrine ophthalmopathy.