[Treatment for recurrent hairy cell leukemia].

AIM: To give data on the frequency of recurrent hairy cell leukemia (HCL) and to characterize the immediate and late results of its treatment in this group of patients. MATERIALS AND METHODS: The data on the frequency of recurrences were analyzed in 165 patients with HCL after remission achieved by the purine analogue cladribin in the period 1995 to 2011. The treatment of recurrent HCL included splenectomy, interferon-a, cladribin, and rituximab. RESULTS: After a course of cladribin therapy, the total frequency of recurrent HCL was 22%. The high (47%) frequency of recurrences was found in young patients (less than 45 years) as compared to that (9%) in older patients. A combination of cladribin and rituximab showed a high efficacy in treating the early recurrence of HCL. CONCLUSION: The differences found in the frequency of recurrences give grounds to incorporate rituximab into the standard therapy regimen for HCL in young patients and in patients with early disease recurrence.

[Long-term results of treatment for T-cell lymphoblastic lymphomas].

AIM: To define the efficiency of the GMALL 2002 program for the treatment of patients with T-cell lymphoblastic lymphomas (T-LBL). SUBJECTS AND METHODS: Twenty-five patients with a verified diagnosis of T-LBL were examined. Male/female ratio was 19:6; median age was 33 (range 16-67) years. There was a preponderance of patients with the generalized stages of the diseases: 2, 5, and 18 with Stages II, III, and IV, respectively. Mediastinal lesion was found in 20 (80%) of the 25 patients. Their treatment was performed according to the GMALL 2002 program and similar CHOP courses. Analysis was made in 2 groups that were not different in their clinical and morphological characteristics. Group 1 consisted of 17 of the 25 patients treated according to the GMALL programs; Group 2 comprised 8 patients who had similar CHOP and other chemotherapy regimens. RESULTS: In Group 1, 15 (88%) patients achieved a complete clinical and hematological remission and 2 (12%) patients died in the first stages of the treatment. No relapses were noted. The median survival had not been achieved; 5-year overall survival was 88 +/- 8%. In Group 2, three patients were alive; 2 completed their treatment; 5 (63%) patients died from treatment failures. The median survival was 23 +/- 18%; 5-year overall survival was 45%. CONCLUSION: The findings suggest that the GMALL 2002 programs are highly effective in treating patients with T-LBL at the first stage of treatment.

Expression level of lipoprotein lipase and dystrophin genes predict survival in B-cell chronic lymphocytic leukemia.

Mutational status of immunoglobulin variable region genes (VH-genes) is known as the strongest predictor of long term prognosis in B-CLL. However, applications in the routine clinical practice are time consuming, and therefore some other predictions are required. In this study, we have compared prognostic values of real time PCR quantification of the expression levels of four genes previously shown to be differentially expressed in V(H)-unmutated and mutated B-CLL subtypes: ZAP-70, ZBTB20, DMD and LPL. The study included 134 B-CLL patients. Expression levels of LPL and DMD genes were significantly correlated to mutational status, while expression levels of of ZAP-70 gene correlated only in CD19+ selected cases (N = 40). No correlation was observed for ZBTB20 gene. Expression levels of LPL and DMD predicted overall survival in the entire cohort of patients. Prognostic values of LPL gene expression levels were significant even for CLL patients with stage A. Quantitative RT-PCR assays for measuring LPL gene expression are robust enough to be introduced into routine clinical practice.

[Cytogenetic disorders in chronic B-cell lymphoid leukemia and their relations with clinicobiological features and prognosis of the disease].

AIM: To study a relationship between cytogenetic disorders, clinicobiological characteristics and prognosis in chronic B-cell lymphoid leukemia (B-CLL). MATERIAL AND METHODS: Cytogenetic examination of blood, bone marrow and lymph node cells from 135 patients (90 males and 45 females aged 23-84 years) with chronic B-CLL was made. The patients were followed up from 1 month to 25 years. Before the cytogenetic examination specific therapy was not given. B-CLL was staged by K. Rai, forms--by A.L. Vorobyev and M.D. Brilliant. All the patients have undergone standard cytogenetic examination, FISH with multicolor probe to loci with possible frequent aberrations (del3q14, del11q23, del17p13, trisomia 12), determination of CD38 antigen expression on circulating tumor cells. Mutation status of the genes of immunoglobulins variable region (IgVH) was defined in 61 patients. RESULTS: Del13q14 was detected in 34 cases, del11q23--in 26, trisomia of chromosome 12--in 17 cases, del 17p13--in 8, absence of q-arm of chromosome 13--in 3 cases. 61 patients had no karyotype defects. Three prognostic groups of the patients were identified: favourable prognosis--patients without disorders of karyotype and one chromosomal aberration--del13q14; intermediate prognosis patients with dell1q23 and trisomia of chromosome 12; poor prognosis--patients with del17p13 and complex disorders of karyotype. CONCLUSION. Cytogenetic study help determine prognosis of B-CLL and detect patients in need of early therapy.

[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.

[Multi-media computer-based chart: modern tool of clinical record keeping]. / Komp'iuternaia multimediinaia istoriia bolezni--sovremennyi instrument vedeniia klinicheskikh protokolov.

AIM: To design the program of computer multimedia case history (MCH) for collection, storage and analysis of information about the patient including diagnostic images; to test MCH for application in telemedical consulting and control over valid conduction of the treatment protocol. MATERIAL AND METHODS: Brief representation of information is reached by integrated multilevel placement of the data on common time axis. Dynamics of the selected parameters is represented as normalized diagrams in the same system axes. Electron tables are filled either by hand or import of the data from individual electron file of all the information about the patient. Diagnostic images and conclusions are obtained from local computer bases of the diagnostic units. Inexpensive commonly used computers allows one to input digital micro- and macrophotos, x-ray images, etc. Monitor information is available from the universal computer net directly from the monitors Geolink-M. RESULTS: MCH was tested in the Hematological Research Center of RAMS. In cooperation with Bryansk diagnostic center N 1 telemedical consulting and some data bases were perfected. The MCH system joints routine activity of the clinic without any problems raising quality of the patients management, facilitating the access to therapeutic and diagnostic information and its analysis. On-line breaking the limits of the controlled parameters and protocols is detected automatically. These events are emphasized by "blocking questions" which must be worked out by the user. The information on the patient can be fully stored on CD-ROM in line with the MCH program providing organization of the data. CONCLUSION: The system is introduced which collects medical information from various sourses and builds up comprehensive representation of the data on the same time axis. The system provides control over implimintation of the protocols of the patients' management, gives a convenient access to medical information, ensures its reliable storage and availability in case of the patients transfer to other medical institutions, facilitates analysis of clinical cases, conduction of medical consulting.

[Morbidity from leukemia and non-Hodgkin's lymphoma in the juvenile population of various territories of Briansk district]. / Zabolevaemost' leikozami i nekhodzhkinskimi limfomami v detskoi populiatsii razlichnykh territorii Brianskoi oblasti.

Annual incidence of acute leukemia (AL) and non-Hodgkin lymphoma (NHL) per 100,000 residents aged 0-15 years has been compared for 6 South-West regions (supervision territory), 21 control regions (comparison territory) and Bryansk city. Childhood population of the supervision territory, radionuclide contaminated after the Chernobyl accident, was 58,600 residents, that of comparison territory and Bryansk city 158,600 and 98,900, respectively (1992). In 1986-1991 59 ALL cases (annual incidence 3.11 per 100,000), 7 ANLL cases (0.38) 2, 1 and 19 of unspecified leukemia, CML, NHL (1.00), respectively, have been registered. Incidence rate and age distribution for both AL and NHL were typical for childhood population of industrial countries. AL incidence was highest in Bryansk city (4.21), in supervision territory it was 4.1, in comparison regions 3.05. There was a statistically significant excess of AL incidence in 1986 among those aged 0-15 years in the supervision territory based on 8 cases (annual incidence 13, 7, a 95% confidence interval 6-27).

[Descriptive analysis of the excess of acute leukemia morbidity among children in Briansh district]. / Deskiptivnyi analiz ekstsessa zabolevaemosti detei ostrymi leikozami v Brianskoi oblasti.

12 cases of ALL, 2 cases of ANLL and 3 cases of NHL have been registered among children aged 0-15 living in 6 Bryansk territory regions exposed to radionuclide contamination after the Chernobyl accident. The study covers the period from 1986 to 1991. There was an excess of acute Leukemia incidence in 1986 as indicated by 7 ALL and 1 ANLL cases. For ALL relative risk was 4.49, p = 0.006. In 2 cases AL was diagnosed before the accident, 2 patients fell ill in June, 2 in July, 1 in August, we have no exact date for 1 patient. Relative risk has never exceeded 1.0 for all the analyzed hemoblastoses within the last 5 years. The Poisson probability of chance occurrence of 8 AL cases in supervision regions during one year is 0.0004. Sex distribution of the cases was atypical either: 7 from 8 patients were boys. Binomial probability is 0.056 under the standard sex ratio 6:5. No evidence was obtained that this high incidence of childhood leukemia extends to neighbour regions of the Gomel, Mogilev and Bryansk territories. The descriptive epidemiological analysis has confirmed the existence of childhood leukemia incidence excess in 1986, but failed to explain its cause. Analysis of incidence rates alone is not enough to confirm connection between leukemia hazard and Chernobyl accident.

[Epidemiologic registry of leukemia and other hemoblastoses in Briansk region as an instrument of investigation of consequences of the accident at the Chernobyl nuclear power plant]. / Epidemiologicheskii registr leikozov i drugikh gemoblastozov v Brianskoi oblasti kak instrument issledovaniia posledstvii avarii na chernobyl'skoi AES.

Beginning from 1986, at Hematological Research Centre (HRC) epidemiological monitoring has been performed on hemoblastoses in Bryansky district, which suffered from the Chernobyl accident more than any other area of Russia. The collection of personal information is organized about each case of disease from all possible sources, diagnosis verification, computer control, storage and analysis of materials. A specialized Register of Blood diseases is created, including demographical and ecological files. Retrospective period of monitoring 1979-1985, afteraccident period-from 1986. In the register 2832 cases were accumulated of hemoblastoses up to 1993. Regions are selected for monitoring with high levels of contamination by 137Cs (15 Ci/sq.km and more), and area for comparison--the other 21 regions of the district. The comparison did not reveal substantial differences. Further epidemiological analysis must be performed. Taking into account dose loads, special studies are initiated.