[Hairy cell leukemia in young patients].

AIM: To characterize clinical symptoms, course, immediate and long-term treatment results in young patients with hair cell leukemia (HCL). MATERIAL AND METHODS: The data on 41 HCL patients were analysed. The diagnosis was made by standard diagnostic protocol for HCL detection. RESULTS: The analysis of the age of 160 HCL patients studied demonstrated high (26%) incidence of HCL at young age. Young patients with HCL had special clinical manifestations and specific long-term outcomes of treatment with standard schemes. CONCLUSION: Differences in occurrence of recurrences after standard therapy make it necessary to consider young HCL patients as a separate group who need adjuvant treatment to prolong remission.

[Clonal chromosomal aberrations in patients with aplastic anemia at the disease onset and transformation].

AIM: To estimate detectability and characteristic features of chromosomal aberrations in bone marrow cells of patients with aplastic anemia (AA). MATERIAL AND METHODS: The trial covered 155 AA patients admitted to the Hematological Research Center in 1987-2002. Cytogenetic study by G-differential staining was performed in 58 patients with AA and 5 patients with AA transforming into myelodysplastic syndrome (MDS) or acute leukemia (AL). Cytogenetic and morphological specimens of the latter's bone marrow were studied retrospectively using fluorescent in situ hybridization (FISH) with DNA probes for detection of monosomia 7 and deletion 7q. RESULTS: Clonal chromosomal aberrations were detected in 4 out of 28 patients. Further examinations revealed no aberrations. Clonal diseases developed in 7 (4.5%) of 155 patients. In 2 patients the disease transformed into paroxysmal nocturnal hemoglobinuria, 5 (3.2%) patients developed variants of MDS and AL. Monosomia 7 or deletion 7q were diagnosed in 3 cases of MDS/AL. In retrospective study of bone marrow specimens of patients with transformation in MDS/AL with monosomia 7, FISH recognized a small elevation over control values in 2 cases. CONCLUSION: Stable clonal chromosomal aberrations are not characteristic of AA. Some AA patients with subsequent MDS/AL may have minor neoplastic clone in the disease onset.

[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.

[Acute lymphoblastic leukemias with aberrations of BCR-ABL genes].

AIM: To develop an original therapeutic strategy in Ph-positive acute lymphoblastic leukemia (ALL). MATERIAL AND METHODS: In November 2001 Hematological Research Center (HRC) initiated the study of chimeric BCR-ABL gene. During the first stage of the study (November 2001-July 2004), 18 primary ALL patients were recruited in HRC, from July 2004 to January 2005--16 patients in HRC, N.N. Burdenko Central Military Hospital, regional Samara hospital. The diagnosis of Ph-positive ALL was established in detection of translocation t(9;22) by standard cytogenetic test or fluorescent hibridization in situ with double signal (D-FISH), or by polymerase chain reaction with reverse transcription (RT-PCR). In detection of aberration of BCR-ABL gene the patients received stem hemopoietic cells, from June 2004 imatinib was added to chemotherapy in the period of induction and consolidation. RESULTS: Incidence rate of BCR-ABL-positive ALL by standard cytogenetic test and D-FISH makes up 20%, by RT-PCR--25%. Differences in chimeric transcripts detectability by different methods may be explained by different sensitivity of the methods. Complete hematological remissions were achieved in the majority of the patients (6 of 8) irrespective of imatinib administration. Achievement of molecular remission in BCR-ABL-positive ALL occurs also in standard chemotherapy but molecular remissions begin 2-4 months later than clinicohematological ones. CONCLUSION: In using imatinib combination with chemotherapy, molecular remission can be achieved simultaneously with hematological one. Long-term results will be analysed later.

[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.

[Morphological, morphometrical, and immunophenotypic characteristics of primary mediastinal B-cell lymphosarcoma]. / Morfologicheskie, morfometricheskie i immunofenotipicheskie kharakteristiki pervichnoi mediastinal'noi B-kletochnoi limfosarkomy.

AIM: To define histological, cytological, computer-morphometric and immunophenotypical features of primary mediastinal B-cell lymphosarcoma. MATERIAL AND METHOD: The study enrolled 43 patients with primary mediastinal B-cell lymphosarcoma (PMBCL) treated in Hematological Research Center from 1994 to 2002. The examination included morphological and immunophenotypical tests, computer morphometry of the cells by histological sections. RESULTS: PMBCL is represented by a composite population of cells of a giant, large and small size (nuclear areas 76.24 +/- 19.99, 37.77 +/- 8.0 and 17.12 +/- 4.34 mcm2. Three types were identified: giant-cell, large-cell and small-cell. A giant-cell type is represented by large and giant cells comprising, on the average, 44 and 31% of overall number of lymphoid cells. A large-cell type is primarily represented by large lymphoid cells (62% of the lymphoid population). Small-size type is represented by small cells (72% of cells). Frequent histological signs are diffuse sclerosis and focal necrosis. Tumor cells have B-cell nature. In the giant and large cell type more than 70% cells express PCNA, in the small cell type--less than 30%. Expression of activation marker CD30 is observed in 18% cases in the giant and large cell types. CONCLUSION: PMBCL is a morphologically heterogenous disease represented by combination of giant, large and small cells with immunophenotypically B-cell nature characterized in a giant cell and large cell type by prominent but in a small cell and large cell type by insignificant proliferative activity. CD30 expression is observed only in giant cell and large cell types.

[Diagnosis of pulmonary lesions in acute respiratory insufficiency in patients with depressed hemopoiesis]. / Porazheniia lëgkikh pri ostroi dykhatel'noi nedostatochnosti u bol'nykh s depressiiami krovetvoreniia.

AIM: To analyse causes of acute respiratory failure (ARF) and methods of diagnosis of pulmonary lesions in patients with depressed hemopoiesis (DH). MATERIAL AND METHODS: 50 patients with DH and ARF were examined according to the protocol including x-ray, computed tomography, fibrobronchoscopy with bronchoalveolar lavage, cytological, bacteriological, virusological studies of the lavage fluid, biopsy of the lung. The algorithm of the protocol is provided. RESULTS: Sensitivity of the lavage fluid in diagnosis of fungal, bacterial, pneumocystic and cytomegaloviral infections was 84, 78, 93 and 93%, respectively. The cytologic examination of the lavage fluid may detect lung infiltration with blood tumors. In complicated diagnostic cases lung biopsy verified pulmonary lesion but its conduction aggravated the patients' condition. ARF patients with DH, bacterial flora, fungi, cytomegalovirus and pneumocystic infection, pulmonary tumor involvement, pulmonary lesions in ATRA-syndrome, non-infectious lesions of the lungs after bone marrow transplantation were found in 38, 18, 40, 18, 8 and 4% of cases, respectively. CONCLUSION: DH patients with ARF should be examined by the protocol including both non-invasive and invasive diagnostic methods. Accurate diagnosis of ARF causes is the basic reserve in the treatment of such patients.

[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).

[Effectiveness of trans-retinoic acid in the treatment of acute promyelocytic leukemia: initial results of a multicenter study]. / Effektivnost' polnost'iu trans-retinoevoi kisloty v terapii ostrykh promielotsitarnykh leikozov: pervye rezul'taty mnogotsentrovogo issledovaniia.

AIM: Evaluation of trans-retinoic acid (ATRA) in combination with cytostatic drugs in treatment of acute promyelocytic leukemia (APL). MATERIALS AND METHODS: In a multicenter study APL was treated according to protocols APL 01.97 and APL 06.87 in 28 patients (14 males and 14 females, median age 36 years). RESULTS: Administration of ATRA in combination with standard program 7 + 3 (cytosine-arabinoside 100 mg/m2 twice a day v.v. day 1-7, daunorubicin 60 mg/m2 v.v. day 1-3) induced a complete remission in 25 patients (90%). Early lethality was 10% (3 patients died). Resistant APL was not registered. Retinoid syndrome was diagnosed in 15 patients, one patient died. 2-year overall and recurrence-free survival made up 72 and 82%, respectively. CONCLUSION: ATRA combination with cytosine-arabinoside and daunorubicin is a novel treatment of acute promyelocytic leukemia providing a high rate of complete remission and long-term survival.

[Clinical manifestations, diagnosis and course of Pneumocystis carinii pneumonia in patients with hematologic diseases]. / Klinicheskie proiavleniia, diagnostika i techenie pnevmotsistnoi pnevmonii u bol'nykh s zabolevaniiami sistemy krovi.

AIM: To characterize clinical, diagnostic and course features of pneumonia caused by Pneumocystis carinii (PC) in hematologic inpatients. MATERIALS AND METHODS: 27 patients with blood diseases were studied. 22 of them had acute respiratory insufficiency and 5 had unclear lung affection. The data from bronchoalveolar lavage (BAL), lung biopsy, serum tests for IgG, IgM anti-PC-antibodies were used for diagnosis of PC-pneumonia. RESULTS: PC-pneumonia was diagnosed in 8 of 27 patients. Clinical manifestations characteristic for PC-pneumonia were not found. In 5 patients the diagnosis was made on the evidence provided by BAL. Lymphocyte count in BAL was elevated to 27.7 +/- 8.7%. Open biopsy of the lung and transbronchial biopsy diagnosed PC-pneumonia in 2 and 1 patients, respectively. Previous BAL examinations failed to detect PC-pneumonia in 2 of them. In all the patients PC-pneumonia was associated with another infection (bacterial, cytomegaloviral). Histologically, the picture of the disease was determined by the severity of the lung affection or its complications. 5 of 8 patients failed treatment with trimethoprim-sulphamethoxazole and died. Marked respiratory insufficiency was registered at PC-pneumonia diagnosis in all the lethal cases. CONCLUSION: Clinical and x-ray pictures of PC-pneumonia in hemoblastosis patients are not specific. All such patients with symptoms of lung infection resistant to antibacterial and antifungal therapy should be examined for PC-pneumonia.

[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.

[Blood lymphocyte ultrastructure in chronic lymphoproliferative diseases]. / Osobennosti ul'trastruktury limfotsitov krovi pri khronicheskikh limfoproliferativnykh zabolevaniiakh.

The authors have found that in chronic B-cell lymphoid leukemia and splenic lymphocytoma the proportion of irregular nuclei diminishes, in some patients split nuclei emerged. The proportion of irregular nuclei in lymphocytoma is significantly higher than that in chronic leukemia. The above diseases are characterized by disordered position of mitochondria in relation to cell center and of this center against nuclear invaginations. Microvilli on the cell surface become less numerous. It is suggested that in chronic lymphoproliferative diseases cytoskeleton in tumor cells may undergo structural and functional alterations.