[Incidence of chronic myeloid leukemia in 6 regions of Russia according to the data of the 2009-2012 population-based study].

AIM: To assess the main epidemiological characteristics of chronic myeloid leukemia (CML) in the Russian Federation. SUBJECTS AND METHODS: A planned epidemiological prospective study was conducted in 2009-2012 in 6 Russian regions with the total number of 10.1 million inhabitants, which notified all new CML cases. RESULTS: The unstandardized (unnormalized, baseline) recorded incidence of CML in the examined regions was 0.58 per 100,000 annually. Its standardized (normalized) incidence was 0.70 for the WHO standard population and 0.72 for the European standard population. The regional variations in the incidence were 0.44 to 0.69. The structural analysis of the incidence in the age strata indicated that the overall morbidity was less due to the decreased rate of registration in old age groups. The morbidity rates in patients aged less than 60 years were nearly similar to the European rates; those in patients aged over 70 years were almost 10 times lower. The lower rate of detection and screening diagnosis of CML in pensioners in primary health care is discussed. CONCLUSION: The data obtained in this study may serve as the starting point for monitoring the CML epidemiological situation.

[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). This study included 8 CML patients (7 in a chronic phase, 1 in acceleration phase) treated with BCR-ABL ITK inhibitors of the first (imatinib) and the second line (ITK-II). The standard cytogenetic examination, on demand--investigation of the interphase nuclei with FISH, in some cases morphological, cytochemical and histological examinations of the bone marrow were made. RESULTS: The existence of a Ph-negative clone with trisomy of chromosome 8 had no negative effect on the course of the disease. The patients showed a stable hematological and cytogenetic response and no need in changing treatment policy. In long-term follow-up Ph-negative clone with trisomy of the chromosome 8 persisted without a clear trend to rise in most patients. CONCLUSION: Detection of a Ph-negative clone with chromosome 8 trisomy at early stages suggests parallel existence of Ph-positive and Ph-negative clones. None of the patients had myelodisplasia.

[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. To September 2008, 16 (89%) patients were alive, 2 (11%) patients died of the disease progression after dasatinib discontinuation. A complete clinicohematological response was observed in all the patients. Major cytogenetic, complete cytogenetic, major molecular, complete molecular responses were achieved in 12 (67%), 10 (55%), 7 (39%) and 5 (28%) patients, respectively. Hematological and non-hematological toxicity occurred in 9 (50%) patients. Now 12 (67%) patients continue dasatinib treatment, in 6 (33%) patients the drug was discontinued. CONCLUSION: The results from trials in Russian Hematological Research Center are the same as in the international study. Dasatinib is effective and well tolerated therapeutic option for imatinib-resistant patients with a chronic phase of CML.

[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.

[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 60.8%. The following aberrations were found most frequently: deletion of the long arm of the chromosome 5 (del(5q)) - 34.6%, trisomy of chromosome 8 (14.1%), monosomy of chromosome 7 (13.4%), aberrations 3q21q26 (12.6%), aberrations of a long arm of X-chromosome (4.7%), the absence of Y-chromosome (3.1%). Complex aberrations of karyotype were found in 13.5% cases. Chromosomal aberrations determined not only clinical and morphological features but also the prognosis of the disease. CONCLUSION: Cytogenetic examination is an essential component of MDS patients examination. It allows more precise classification of MDS variant and prognostification of the disease course.

[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.

[Therapeutic efficacy of imatinib mesylate (glivec) in chronic phase of myeloid leukemia]. / Effektivnost' terapii imatiniba mezilatom (glivekom) v khronicheskoi faze mieloleikoza.

AIM: To evaluate efficacy and tolerance of glivek in chronic myeloid leukemia (CML) in patients who failed interferon-alpha (If-a) preparations. MATERIAL AND METHODS: 79 patients in a chronic phase of Ph + CML with hematological and cytogenetic resistance or intolerance of If-a. The response to glivec was assessed by achievement of a complete hematological remission and the cytogenetic effect (the degree of reduction of cell clone Ph+ in bone marrow). Tolerance and safety of the drug was studied by monthly standard clinicohematological tests. RESULTS: Not only a hematological remission (92.4%), but also partial (46.8%) or complete (27.8%) elimination of BCR-ABL +/- cells were achieved after 12 months of the treatment. Glivec was well tolerated. Hematological toxicity primarily as neutropenia and thrombocytopenia were observed in 54.4 and 42% patients, respectively. Neutropenia of the third degree which made impossible to continue the treatment was observed in 29.1% patients; throbocytopenia of the third degree was registered in 16.5% patients. Among most frequent non-hematological side effects there were moderate edema, nausea, leg muscle convulsions, weight gain, arthralgias, skin eruption. All the complications were transient, were managed in all cases with only a short-time discontinuation of glivec therapy. CONCLUSION: High activity of glivec at early stages of CML allows using this drug as a first-line therapy in patients with CML.

[T-cell tumors with aplastic syndromes]. / T-kletochnye opukholi, protekaiushchie s aplasticheskimi sindromami.

AIM: To detect and verify the existence of a specific form of T-cell tumor accompanied by isolated lesions of bone marrow and aplastic syndromes. MATERIAL AND METHODS: Four patients with aplastic syndromes were examined using clinical, histological, cytological, cytogenetic, and immunophenotypic methods. RESULTS: Four cases of T-cell tumors of bone marrow with clinical and morphological manifestations of aplastic syndrome and scanty proliferation activity in bone marrow alone were diagnosed. The proliferation activity in bone marrow was observed as formation of small clusters composed of small-size lymphoid cells with dense nucleus. Dynamic monitoring of two patients revealed a trend toward an increase in the lymphoproliferation base against the remaining clinical picture of aplastic syndrome. The T-cell immunophenotype characterized by disappearance of some markers or decrease in their density, was observed only in some blood and bone marrow lymphocytes. The most significant changes of immunophenotype were observed in one of the patients (CD2+CD3-CD4-CD5-CD7-CD8-CD16-CD56-CD45RO++). The same patient had pronounced cytogenetic changes (47XY+Y[8], 47, XY, del(1)(p10) [23], 46 XY [3]) and resistance to routine therapy, including cyclosporin. In one patient the process transformed into lymphosarcoma. CONCLUSION: The results obtained in four patients allow their clinicomorphological characteristics to be regarded as particular forms of T-cell tumors accompanied by bone marrow damage and aplastic syndrome.

[Clinical significance of erythrocyte ferritin in refractory anemia and chronic myeloid leukemia]. / Klinicheskoe znachenie ferritina éritrotsitov pri refrakternykh anemiiakh i khronicheskom mieloleikoze.

AIM: To find out if the RBC ferritin elevation can serve as an additional criterion of inefficient erythropoiesis during progression of chronic myeloid leukemia (CML) and in various types of refractory anemia. MATERIAL AND METHODS: The study group consisted of 56 MDS patients and 73 patients at various stages of CML. 20 healthy donors and 105 patients with verified inefficient erythropoiesis (20--with B12 deficiency before and after the treatment, 85--with beta-thalassemia) were the controls. A ferritin level was measured by radioimmunoassay in RBC hemolysates. RESULTS: The RBC ferritin level in all types of refractory anemia was elevated throughout the disease course, increasing with the development of transfusion dependency. The CML progression was also accompanied by RBC ferritin level elevation associated with abnormal erythroid cell accumulation and elevation of intracellular PAS-positive substance (p < 0.05). CONCLUSION: RBC ferritin level elevation can be considered as an additional biochemical criterion of inefficient erythropoiesis that may be useful in differentiation of anemias, adequate therapy selection and follow-up of erythropoiesis.

[The prognostic criteria in the primary myelodysplastic syndrome]. / Prognosticheskie kriterii pri pervichnom mielodisplasticheskom sindrome.

Basing on computer processing of 126 primary clinical and laboratory parameters obtained from 92 patients with myelodysplasia and using multifactorial regression analysis, the authors have developed prognostic models of life span and probability of transformation into acute leukemia. The model of life span enabled recognition of 3 prognostic groups of myelodysplasia patients: of high (median 10 months), moderate (median 22 months) and low (median 35 months) risk. This makes it possible to prognosticate the disease and assume optimal therapeutic policy.