[Detection of minimal residual disease in patients with acute myeloid leukemia]. / Vyiavlenie minimal'noi ostatochnoi bolezni u bol'nykh ostrymi mieloidnymi leikozami.

AIM: Detection of minimal residual disease (MRD) in patients with acute myeloid leukemia (AML) and the study of its correlations with duration of recurrence-free interval. MATERIAL AND METHODS: Bone marrow samples obtained from 37 AML patients before treatment were studied at two-color flow cytometry. The panel of monoclonal antibodies to T- and B-cell, myeloid antigens was used. The residual cells were estimated in 20 patients in remission. RESULTS: 78% cases were diagnosed to have an anomalous immunophenotype including coexpression of lymphoid and myeloid antigens, asynchronous expression of myeloid antigens. In the first remission the residual cells were detected in 20 patients due to aberrant antigen expression. The presence of MRD was stated if bone marrow contained more than 0.12% leukemic cells. The duration of the first remission and MRD correlated. 8 patients with MRD had remission for 3 to 6 months (median 4.7 months). 12 patients free of MRD were in remission for more than 6 months (for 8 to 26 months, median 19.7 months). The threshold level of the residual cells (0.12%) was confirmed statistically using the three-parameter probability model. CONCLUSION: This study confirms feasibility of using flow cytometry for detection of residual cells. MRD and duration of the first remission correlate. Long-term observation of large groups of AML patients will try the validity of the above statistical model.

[Effectiveness of cyclosporin A in the treatment of adult patients with aplastic anemia]. / Effektivnost' tsiklosporina A v lechenii vzroslykh bol'nykh aplasticheskoi anemiei.

AIM: To evaluate the efficacy of cyclosporin A (CyA) at different stages of immunosuppressive therapy (IST) in patients with aplastic anemia (AA). MATERIALS AND METHODS: The efficacy of CyA was studied in 56 patients with AA. The agent was orally given in an initial dose of 10 mg/kg as solution or capsules. Its daily dose during a treatment course varies with the serum CyA levels and clinical tolerance. CyA was used in 17 patients at the first stage of treatment, in 8 with recurrent AA, and in 31 after ineffective previous therapy (antilymphocytic globulin therapy--ALGT, splenectomy). Erythropoiesis was evaluated by the count of erythrokaryocytes and by relative erythroid hyperplasia of the bone marrow and by using erythrokaryocytic PAS reaction, by calculating the total count of sideroblasts and ringed sideroblasts. RESULTS: A positive response was obtained in 41% of the patients with AA. Its pattern depended on the severity of AA, on CyA use regimens, and treatment duration: when treatment with CyA lasted 6-12 months, its efficacy considerably increased (positive responses in severe AA and mild AA being in 64 and 94%, respectively). It has been found that high (over 6%) baseline bone marrow ringed sideroblasts in patients with AA may be regarded as a poor predictor in the context of the efficacy of this agent. CONCLUSION: CyA is recommended for combined IST in patients with AA at the second stage of treatment (after antilymphocytic globulin administration) in order to perform long-term (12-month) immunosuppression by choosing the optimum dose on an individual basis and by continuously monitoring the quality of a response.

[Results of clinical trials in the treatment of acute myeloid leukemia in adults during a 7-year period]. / Rezul'taty provodimykh v techenie 7 let klinicheskikh issledovanii po lecheniiu ostrykh mieloidnykh leikozov vzroslykh.

AIM: Comparison of effectiveness of induction regimens varying in intensity and maintenance variants in patients with acute myeloid leukemia (AML) included in a randomised multicenter trial. MATERIALS AND METHODS: Clinical trial 1 enrolled 185 AML patients. Vepesid-free induction was used in 85 patients (group 1), induction with vepesid--in 99 patients (group 2). 223 AML patients entered trial 2. Of them 37 patients were treated for 3 years 7 + 3 with daunorubicin in the dose 45 mg/m2 in the induction phase (group 1), 85 and 101 patients received 7 + 3 with daunorubicin for a year in the dose 45 mg/m2 and 60 mg/m2, respectively, (group 2 and 3). RESULTS: For group 1 in trial 1 the remission rate, early lethality, resistance were, respectively, 60, 20 and 20%, respectively. For group 2 in trial 1--66, 22 and 12%, respectively. 5-year recurrence-free survival reached 32 and 37% for group 1 and 2, respectively. For trial 2 relevant figures made up 75.5, 16.2, 8.1% for group 1; 60, 17.6 and 22.4% for group 2; 63, 20.8 and 16% for group 3, respectively. The 3.5-year recurrence-free survival in groups 1, 2 and 3, was 16, 46 and 50%, respectively. For both trials, the differences between the groups were insignificant. CONCLUSION: The results evidence that the treatment can be shorter (not 3 but 1 year or even 6 months), the induction more intensive (the dose of anthracycline antibiotics can be elevated up to 60 mg/m2 without a rise in early lethality).

[Fevers of unknown origin: new aspects of an old problem]. / Likhoradki neiasnoi étiologii: novye aspekty staroi problemy.

Fever is an important component of immune response of the organism to various stimulating effects (trauma, infection, inflammation). This complex process comprises activation of monocytes/ macrophages, their synthesis and secretion of proinflammatory cytokines and realization of multiple biological effects of cytokines including growth stimulation and differentiation of hemopoietic cells. Recently, there has appeared a trend to growing number of cases with uncommon hyperthermia and 2-3 germ cytopenia in the blood. Activation of the macrophage system and hyperproduction of proinflammatory cytokines can be viewed not only as an essential mechanism of hemopoiesis stimulation but also as a potential cause of hemodepression. The paper analyzes the relations between high functional activity of the macrophage system and development of cytopenia in patients with persistent fever. Functional activity of the macrophage system was studied on the model of patients with tumors or reactive proliferations of monocytes-macrophages as the latter are the main sources of IL-1-cytokine--a mediator of human fever. To prove the suggested correlation and its significance, a correlation analysis was made of 29 clinical and laboratory parameters in 184 patients and 100 controls.

[The treatment of aplastic anemia with antilymphocyte globulin]. / Lechenie aplasticheskoi anemii antilimfotsitarnym globulinom.

Made in Russia antilymphocytic globulin (ALG) was given to 43 patients with aplastic anemia (AA). 56% of the patients responded, 30% reached a complete or partial remission. 5-year actuarial survival of ALG-treated patients was 52% (44 and 60% for severe and non-severe forms). The data on ALG efficacy suggest its benefits in first-line therapy of both severe and non-severe AA as well as in management of patients resistant to other methods of immunosuppressive treatment.

[Lymphocytoma of the spleen--a separate nosological form requiring a specific management procedure]. / Limfotsitoma selezenki--otdel'naia nozologicheskaia forma, trebuiushchaia spetsificheskoi taktiki vedeniia.

The paper presents new findings in favor of recognition of splenic lymphocytoma (SLC). This disease was characterized by A. I. Vorob'ev and M. D. Brilliant in 1982 in terms of detailed clinicomorphological features, prognosis and optimal treatment policy. The study included 52 patients (mean age 53 years) of which 36 were females and 16 males. They were followed up for 5.7 years, on the average. SLC manifested clinically by splenomegaly with minimally enlarged lymph nodes, morphologically by nodular lymphocytic proliferates in the spleen, bone marrow and liver, diffuse or diffuse-nodular proliferation in the lymph node. Peripheral blood contained middle-size lymphoid cells with round nuclei. SLC immunophenotype exhibits moderate or marked expression of CD22 and membrane immunoglobulins, the absence of CD5, CD23 and EM receptor, combination of CR1-/ CR2+. Paraprotein secretion was recorded in 49% of cases. There were frequent autoimmune reactions, especially against erythroid cells and platelets (42%). Optimal therapeutic policy is expectation and eventual splenectomy producing a persistent clinical effect in 94% of patients. In progressive disease long-term therapy with cyclophosphamide is recommended. Thus, SLC is a mature-cell lymphatic tumor growing as a rule in the spleen. Its prognosis in valid therapy is favourable.

[The clinico-hematological indices of the participants in the cleanup of the aftermath of the Chernobyl accident]. / Kliniko-gematologicheskie pokazateli uchastnikov likvidatsii posledstvii Chernobyl'skoi avarii.

Clinicohematological investigations and cytogenetic analysis of blood lymphocytes were made 5-7 years after the Chernobyl accident in 201 liquidators who had worked in the radionuclide-contaminated zone. Among the somatic diseases found in the examinees statistically more prevalent were cardiovascular and gastrointestinal affections, asthenic syndrome, thyroid disorders. Hemograms presented a rise in hemoglobin, red cell and eosinophil content, a drop in the number of neutrophils. A tendency to erythrocytosis was observed in 20.3% of the wreckers. Dicenters and rings were abundant in the lymphocytes of 69% of the cytogenetically examined examinees 5-7 years after the exposure to radiation.

[Acute respiratory insufficiency in hemoblastoses: evaluation of treatment effectiveness by survival rate]. / Ostraia dykhatel'naia nedostatochnost' pri gemoblastozakh: otsenka éffektivnosti terapii po vyzhivaemosti.

Acute respiratory failure (ARF) is a typical complication of chemotherapy for hematologic malignancies. Despite the effective correction of gas exchange by mechanical ventilation, the mortality in this population is expected to be extremely high due to unavoidable fatal infection of immunocompromised host and the poor prognosis of primary malignancy. However, modern specific treatment of leukemia and lymphoma has made these conditions curable in many cases, and even severe myelotoxic neutropenia does not always lead to uniformly fatal outcome. We studied survival in 113 cases of ARF retrospectively selected according to the uniform criteria of this syndrome. No selection was made as to the diagnosis, stage, and response to the treatment of the underlying disease. The group consisted of 51% male and 49% female patients aged 34, on an average; 69% of these with acute leukemia, 22% with malignant lymphoma, and 9% with other conditions. Sixty-five (58%) patients were subjected to mechanical ventilation (MV). Forty-two were treated after a Protocol on intensive care of ARF which contained standard requirements to management of patients. Another group of 71 patients admitted to intensive care units before this Protocol was introduced were historical controls. Total survival was 19.5%. In the MV group survival was 15% with 10 cases of cure, ARF developing during severe neutropenia in 3 out of these 10 cases. The results became evidently better after the Protocol was introduced, improving from 16 to 27%. The primary disease dramatically influenced the results: long-term survival was significantly poorer in patients with relapses and resistant to chemotherapy, with 100% mortality within 8 months after discharge. A conclusion is drawn that intensive care of ARF including MV is justified in patients with hematologic malignancies, except cases when primary malignancy is not properly treated or resistant to specific chemotherapy.

[Phenotypic variability and correlation between skinfold thickness and arterial pressure level]. / Fenotipicheskaia izmenhivost' i vzaimosviaz' tolshchiny kozhnoi skladki i urovnia arterial'nogo davleniia.

Contribution of genetic and environmental factors in phenotypic variability of blood pressure level and skinfold thickness, and phenotypic correlation between these characters was calculated on the basis of familial correlations. It was shown that genetic determinant explains considerable portion of blood pressure level and skinfold thickness variability. Among common environmental effects, the factors affecting one generation are important with regard to variability of these characters. Maternal effect is expressed in the variability of systolic and diastolic blood pressure. Correlation between blood pressure level and triceps skinfold thickness is determined by genetic factors, whereas that between blood pressure level and subscapular skinfold thickness is mediated by environmental factors. The results obtained may be applied in populational prevention of cardiovascular disease.

[The role of genetic and environmental factors in phenotypic variability of arterial pressure and body weight and their interconnection (a family study)]. / Rol' geneticheskikh i sredovykh faktorov i fenotipicheskoi izmenchivosti arterial'nogo davleniia i massy tela i v ikh vzaimosviazi.

Contribution of genetic and environmental factors into phenotypic variability of blood pressure and body mass as well as into phenotypic correlation between these traits was defined. It was shown that additive genetic determinant is responsible for considerable level of blood pressure and body mass variability. Those common environmental factors are of importance which operate within the limits of one generation. Maternal effect of systolic and diastolic blood pressure variability is negligible. The correlation between systolic and diastolic blood pressure is determined both by environmental and genetic factors, whereas that between blood pressure and body mass is mediated by only environmental factors. The contribution of environmental factors into correlation between blood pressure and body mass lessens with age. The results obtained may be applied in development of population and individual programmes for preventing cardiovascular diseases.

[Role of genetic and environmental factors in the determination of body weight and skinfold thickness in children having different blood pressure (a familial study)]. / Rol' geneticheskikh i sredovykh faktorov v determinatsii massy tela i tolshchiny kozhnykh skladok u detei s raznym urovnem arterial'nogo davleniia (semeinoe issledovanie).

Based on intrafamilial correlations, a component genetic analysis was used to evaluate the contribution made by genetic and environmental factors to variance in body weight and skin fold thickness in children who had various blood pressure. In children with initially elevated and normal blood pressures, the phenotypic variation in the body weight and adipopexia is largely determined by genetic factors, whereas in those with initially lower blood pressure, the phenotypic variation in the above parameters is greatly affected by environmental factors, mainly by those of occasional nature. The findings provide evidence for a differential approach to the primary prevention of hyper- and hypotension in children and adolescents.

Factors determining arterial blood pressure in childhood.

As part of a programme designed to determine precursors of arterial hypertension and atherosclerosis in children and adolescents, a cross-sectional study involving the groups of families whose children had different baseline arterial pressure levels was conducted. An association between the level of arterial pressure in the children and the blood pressure levels and prevalence of cardiovascular diseases in their first-degree relatives was found. The most informative signs for decreased and increased arterial blood pressure levels in children were identified. The findings should be taken into account when selecting groups of children who require close medical surveillance.

[Role of genetic and environmental factors in determination of arterial blood pressure level]. / Rol' geneticheskikh i sredovykh faktorov v determinatsii urovnia arterial'nogo davleniia.

Three groups of families with different initial levels of arterial pressure in proband children were examined. The relationship was established between the levels of arterial pressure in children and those in their relatives of the first degree of kinship. Based on intrafamilial correlations, the phenotypic dispersion of systolic and diastolic arterial pressure was analyzed. It has been shown that as compared to the genetic factors, the environmental factors play a greater role in arterial pressure variability.