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1.
Ter Arkh ; 89(12): 86-96, 2017.
Article in Russian | MEDLINE | ID: mdl-29411766

ABSTRACT

AIM: To assess the results of following up patients with chronic myeloid leukemia (CML) and a deep molecular response (MR) without tyrosine kinase inhibitor (TKI) therapy. SUBJECTS AND METHODS: The reasons for TKI discontinuation in 70 patients with CML and a deep MR of more than 1 year's duration were adverse events, pregnancy, and patients' decision. Information was collected retrospectively and prospectively in 2008-2016. RESULTS: The median follow-up after TKI therapy discontinuation was 23 months (2 to 100 months). At 6, 12 and 24 months after TKI therapy discontinuation, the cumulative incidence of major MR (MMR) loss was 28, 41 and 48%, respectively; the survival rates without TKI therapy were 69, 50, and 39%, respectively. MMR loss was noted in 28 (88%) patients at 12 months; it was not seen without TKI therapy at 2-year follow-up. Deaths due to CML progression were absent. The Sokal risk group was a reliable factor influencing MMR loss (p ≤ 0.05). The cumulative recovery rate for deep MR after resumption of TKI use was 73 and 100% at 12 and 24 months, respectively, with a median follow-up of 24 months (1 to 116 months). Deep MR recovered at a later time when the therapy was resumed more than 30 days after MMR loss. CONCLUSION: Safe follow-up is possible in about 50% of the patients with CML and stable deep MRs without TKI therapy. The introduction of this approach into clinical practice requires regular molecular genetic monitoring and organizational activities. Biological factors in maintaining remission after TKI discontinuation need to be separately studied.


Subject(s)
Dasatinib , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Pyrimidines , Withholding Treatment/statistics & numerical data , Adult , Aftercare/methods , Aftercare/statistics & numerical data , Dasatinib/administration & dosage , Dasatinib/adverse effects , Disease Progression , Female , Humans , Imatinib Mesylate/administration & dosage , Imatinib Mesylate/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Male , Middle Aged , Molecular Imaging/methods , Outcome and Process Assessment, Health Care , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Risk Assessment , Russia
2.
Ter Arkh ; 88(1): 89-95, 2016.
Article in Russian | MEDLINE | ID: mdl-26978616

ABSTRACT

Patients with myeloproliferative diseases (MPD) are noted to be at high risk for portal thromboses. This problem gives rise to disability if it is untimely treated or resistant to therapy. The paper gives the experience of the Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation, in using antithrombin III in MPD patients (3 patients with primary myelofibrosis, 3 with essential thrombocythemia) and acute and subacute portal vein thromboses resistant to therapy with direct anticoagulants. In all 5 cases, the use of antithrombin III in combination with low-molecular-weight heparin showed a positive clinical effect as rapid relief of pain syndrome and comparatively early (3-week to 1.5-2-month) recanalization of thrombosed vessels. Three clinical cases are described in detail.


Subject(s)
Antithrombin III/administration & dosage , Budd-Chiari Syndrome , Heparin, Low-Molecular-Weight/administration & dosage , Primary Myelofibrosis , Thrombocythemia, Essential , Adult , Blood Coagulation/drug effects , Blood Coagulation Tests/methods , Budd-Chiari Syndrome/blood , Budd-Chiari Syndrome/diagnosis , Budd-Chiari Syndrome/etiology , Budd-Chiari Syndrome/physiopathology , Budd-Chiari Syndrome/therapy , Drug Monitoring/methods , Female , Fibrinolytic Agents/administration & dosage , Humans , Portal System/diagnostic imaging , Portal System/physiopathology , Primary Myelofibrosis/blood , Primary Myelofibrosis/complications , Primary Myelofibrosis/diagnosis , Primary Myelofibrosis/physiopathology , Primary Myelofibrosis/therapy , Thrombocythemia, Essential/blood , Thrombocythemia, Essential/complications , Thrombocythemia, Essential/diagnosis , Thrombocythemia, Essential/physiopathology , Thrombocythemia, Essential/therapy , Treatment Outcome , Ultrasonography , Vascular Patency/drug effects
3.
Ter Arkh ; 86(7): 37-44, 2014.
Article in Russian | MEDLINE | ID: mdl-25314776

ABSTRACT

AIM: To determine the clinical features of multiple primary tumors (MPT) in patients with hemoblastoses, to develop treatment policy for synchronous and metachronous tumors, and to determine the impact of chemotherapy for one disease on the course and prognosis of another one. SUBJECTS AND METHODS: The investigation included 20 patients with multiple primary synchronous and metachronous myeloid and lymphoid tumors, who had been followed up at the Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation. The distribution of patients by nosological entities was as follows: 17 (85%) patients with myeloproliferative diseases (MPDs) concurrent with lymphoproliferative diseases (LPDs) and 3 (15%) with two types of MPD. A special group comprised 3 patients who successively developed 3 malignant diseases: cancer/B-cell chronic lymphocytic leukemia (B-CLL)/Ph-positive chronic myeloid leukemia (Ph+CML); cancer/polycythemia vera (PCV)/B-CLL; cancer/essential thrombocythemia (ETC)/multiple myeloma (MM). RESULTS: The Outpatient Department of the Hematology Research Center, Ministry of Health of the Russian Federation, followed up 20 patients with synchronous and metachronous tumors in 1996 to 2013. The patients' age was 42 to 82 years (64 years). The female/male ratio was 1:1.2. Metachronous tumors were 1.5-fold higher than synchronous ones. The time to detection of secondary hemoblastosis averaged 3.3 years; the longest interval was 14 years; the mean coexistence of 2 tumors was 4.8 years (1-11 years). The total length of the follow-up was 8 years (1-19 years). Among them, there were 17 (85%) patients with 2 chronic hematologic tumors with a myeloid or lymphoid phenotype; 3 (15%) of the 20 patients had 3 malignant diseases (cancer/ B-CLL)/Ph+CML, cancer/PCV/B-CLL, cancer/ETC/MM. In the group of 17 patients, 13 (76%) were diagnosed as having Ph-negative MPDs (PCV in 4 patients, primary myelofibrosis in 4, ETC in 4, undifferentiated MPD in1) and 4 (24%) patients had Ph+CML. This patient group was found to have the following LPDs: CLL in 5 (30%), hairy cell leukemia in 1 (5%), paraproteinemic hemoblastoses in 11 (65%). MPD preceded LPD in 8 (47%) patients; the development interval between two tumors averaged 6 years (1 to 14 years). LPD preceded MPD in 3 (18%) patients; the interval averaged 5 years (2 to 17 years). MPD and LPD appeared synchronously in 6 (35%) patients. CONCLUSION: The fact that 2 malignancies or more may occur in one patient determines the need for a careful follow-up of patients with blood system diseases. The activity of one hematologic disease or another is a leading criterion for choosing a therapeutic tactic.


Subject(s)
Hematologic Neoplasms/diagnosis , Hematologic Neoplasms/etiology , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/etiology , Neoplasms, Second Primary/diagnosis , Neoplasms, Second Primary/etiology , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/epidemiology , Humans , Male , Medical Records , Middle Aged , Neoplasms, Multiple Primary/drug therapy , Neoplasms, Multiple Primary/epidemiology , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/epidemiology , Retrospective Studies
4.
Ter Arkh ; 86(12): 127-34, 2014.
Article in Russian | MEDLINE | ID: mdl-25804054

ABSTRACT

The term mastocytosis (MC) encompasses a group of rare diseases characterized by the tumorous proliferation of clonal mast cells and the infiltration of one or several organs. The clinical picture of MC is extremely diverse from skin lesions that can spontaneously regress to the aggressive disease forms associated with organ dysfunction and short survival. Nowadays, the 2008 WHO classification identifies 7 MC subtypes. The disease is diagnosed on the basis of its clinical manifestations and detection of tumorous mast cell infiltrations via morphological, immunohistochemical, immunophenotypic, genetic, and molecular examinations. Abnormal mast cells are characterized by the atypical morphology and pathological expression of CD25 and CD2 antigens. Enhanced serum tryptase activity is a common sign in all MC subtypes. More than 90% of the patients have D816V KIT mutations in the mast cells. This paper reviews the literature. Three cases are described as a clinical example in patients with different MC subtypes.


Subject(s)
Mastocytosis , Adult , Female , Humans , Mastocytosis/complications , Mastocytosis/diagnosis , Mastocytosis/therapy
5.
Klin Lab Diagn ; (7): 24-8, 2012 Jul.
Article in Russian | MEDLINE | ID: mdl-22988798

ABSTRACT

The mutation V617F of gene JAK2 is detected in 95% of patients with genuine polycythemia, in 50% of patients with essential thrombocytemia and idiopathic myelofibrosis. The mutation V617F can be applied as a molecular marker of response to treatment in patients with chronic myeloproliferative diseases associated with this mutation. The technique of quantitative evaluation of V617F (sensitivity up to 0.01%) using polymerase chain reaction is described. This method can be applied to assess the minimal residual disease in patients with chronic myeloproliferative diseases.


Subject(s)
Chronic Disease , Janus Kinase 2/blood , Mutation , Myeloproliferative Disorders/blood , Adolescent , Adult , Aged , Aged, 80 and over , Cell Line , Child , Evaluation Studies as Topic , Humans , Janus Kinase 2/genetics , Middle Aged , Myeloproliferative Disorders/genetics , Polycythemia/blood , Polycythemia/genetics , Primary Myelofibrosis/blood , Primary Myelofibrosis/genetics , Thrombocythemia, Essential/blood , Thrombocythemia, Essential/genetics
6.
Ter Arkh ; 81(7): 29-36, 2009.
Article in Russian | MEDLINE | ID: mdl-19708570

ABSTRACT

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.


Subject(s)
Bone Marrow Cells/drug effects , Chromosomes, Human, Pair 8/genetics , Fusion Proteins, bcr-abl/antagonists & inhibitors , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Philadelphia Chromosome/drug effects , Protein Kinase Inhibitors/therapeutic use , Trisomy , Adult , Benzamides , Bone Marrow Cells/enzymology , Bone Marrow Cells/pathology , Drug Administration Schedule , Female , Humans , Imatinib Mesylate , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Middle Aged , Piperazines/administration & dosage , Piperazines/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , Time Factors
7.
Ter Arkh ; 79(8): 17-22, 2007.
Article in Russian | MEDLINE | ID: mdl-17926465

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Myeloid, Chronic-Phase/drug therapy , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Adolescent , Adult , Aged , Benzamides , Blast Crisis/epidemiology , Blast Crisis/pathology , Disease Progression , Female , Follow-Up Studies , Hematopoiesis/drug effects , Humans , Imatinib Mesylate , Incidence , Leukemia, Myeloid, Chronic-Phase/mortality , Leukemia, Myeloid, Chronic-Phase/pathology , Leukocyte Count , Male , Middle Aged , Prognosis , Protein-Tyrosine Kinases/antagonists & inhibitors , Risk Factors , Russia/epidemiology , Survival Rate/trends , Time Factors
8.
Bull Exp Biol Med ; 144(2): 181-4, 2007 Aug.
Article in English | MEDLINE | ID: mdl-18399275

ABSTRACT

We evaluated the content of early and late cobblestone area-forming cells, immediate progeny of hemopoietic stem cells, and committed precursor cells in the bone marrow and peripheral blood of patients with chronic myeloproliferative diseases and healthy donors. In patients with essential thrombocythemia, the number of late cobblestone area-forming cells in the peripheral blood decreased, while other parameters did not differ from those in healthy donors. In patients with idiopathic myelofibrosis, we found a decreased number of late and early cobblestone area-forming cells in the bone marrow and late cobblestone area-forming cells in the peripheral blood, while the count of early cobblestone area-forming cells in the peripheral blood increased. In patients with chronic myeloid leukemia, the number of early cobblestone area-forming cells in the bone marrow decreased, but the count of late and early cobblestone area-forming cells in the peripheral blood increased. The number of endogenous committed precursor cells in the peripheral blood increased in all groups of patients with chronic myeloproliferative diseases and, particularly, in patients with idiopathic myelofibrosis and chronic myeloid leukemia. Functional characteristics of immediate descendants of hemopoietic stem cells probably reflect the level of damage and attest to the existence of various mechanisms underlying the defect of the hemopoietic stem cell during chronic myeloproliferative diseases.


Subject(s)
Hematopoietic Stem Cells/pathology , Myeloproliferative Disorders/pathology , Blood Cells/pathology , Bone Marrow Cells/pathology , Case-Control Studies , Chronic Disease , Colony-Forming Units Assay , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Myeloproliferative Disorders/blood , Primary Myelofibrosis/blood , Primary Myelofibrosis/pathology , Thrombocythemia, Essential/blood , Thrombocythemia, Essential/pathology
9.
Gematol Transfuziol ; 38(7): 17-20, 1993.
Article in Russian | MEDLINE | ID: mdl-8307282

ABSTRACT

Ultrasonic and radionuclide investigations of the lymph nodes have been performed in 342 patients with malignant lymphoproliferative diseases. A comparative analysis of the data obtained by sonography and indirect lymphoscintigraphy has specified diagnostic spectrum of these procedures. The accuracy and specificity of sonography and broad-scale visualization secured by it dictate primary usage of the procedure as a screening test in initial examinations and as a control sensitive estimator of the on-going treatment efficacy. Indirect lymphoscintigraphy is recommended as an adjuvant to echography for detailing topics and nature of the lymph node lesion and to assess the process above the diaphragm. Frequency and regimen of the examinations should be based on clinical demands.


Subject(s)
Lymph Nodes/diagnostic imaging , Lymphoproliferative Disorders/diagnostic imaging , Adolescent , Adult , Aged , Humans , Male , Middle Aged , Radionuclide Imaging , Ultrasonography
15.
Antibiotiki ; 22(8): 756-8, 1977 Aug.
Article in Russian | MEDLINE | ID: mdl-334058

ABSTRACT

The data on the clinical trials of karminomycin, a new antitumor antibiotic are presented. The drug was used in the treatment of 46 adult patients with leukemia. Karminomycin was used in primary inducing therapy and treatment of relapses. The results of the trials showed that karminomycin had a definite therapeutic activity in treatment of acute myeloblast leukemia at various stages of the process. A rapid effect of the antibiotic provided its use in emergency cases with rapidly progressing variants of the disease.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Carubicin/administration & dosage , Leukemia, Lymphoid/drug therapy , Leukemia, Myeloid, Acute/drug therapy , Adult , Bone Marrow/drug effects , Clinical Trials as Topic , Daunorubicin/therapeutic use , Drug Evaluation , Drug Tolerance , Humans , Time Factors
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