RESUMO
BACKGROUND: Withdrawal syndrome (WS) a musculoskeletal pain after discontinuation of tyrosine kinase inhibitors (TKI) in patients with chronic myeloid leukemia (CML) has been described in the treatment-free remission (TFR) studies. The pathophysiological mechanisms and predisposing factors of WS have not been well established. AIM: Our aim was to evaluate clinical features and factors associated with WS in the Russian cohort of CML patients who discontinued TKI therapy. MATERIALS AND METHODS: WS was evaluated in total of 183 CML patients with chronic phase and sustained deep molecular response (DMR). WS was defined as a musculoskeletal pain newly observed after TKI cessation or as a worsening of previously observed symptoms. RESULTS: DMR loss free survival at 36 months was 49% and 43% in prospective and retrospective groups respectively (p=0.96) with mеdian (Me) time of observation 33 months (range 1136). WS was observed in 49 (27%) patients: grade 12 was in 45 (92%) patients, grade 3 in 4 (8%) patients. Me time to WS occurrence was 2 months (range 17), Ðе duration of WS was 5 months (range 135). WS was resolved in 14 of 15 patients with molecular relapse after 13 months of TKI re-initiation and was decreased in 1 patient. WS was completely resolved in 31 of 34 patients who continued remained in TFR and decreased in 3 patients. WS was resolved spontaneously or with nonsteroidal anti-inflammatory drugs in 14 (45%) and 17 (55%) patients accordingly. Older age (p0.0001), longer duration of TKI therapy (p0.0001) and presence of locomotion system diseases (p=0.022) were observed in patients with WS. No WS was observed in pregnant patients (Ñ0.001). Survival without DMR loss at 12 months after TKI stop was 66 and 42% in patients with and without WS accordingly (Ñ=0.095). CONCLUSION: The rate of WS was 27% that is in a good concordance with the data of the other TFR studies. A longer period of TKI exposure, older age and the history of locomotion system diseases were associated with the development of the WS. We found for the first time that WS was not observed in patients with pregnancy. There was no association of WS development and the rate of molecular relapses.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Dor Musculoesquelética , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Dor Musculoesquelética/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Recidiva , Anti-Inflamatórios/uso terapêuticoRESUMO
Myeloproliferative disease associated with FGFR1 rearrangement (8p11), which is included in the 2008 WHO Classification of Myeloid Neoplasms, is a rare and extremely aggressive abnormality. The paper describes a clinical case of a 39-year-old female patient who was detected to have leukocytosis (as high as 47.2·109/l), absolute eosinophilia (as high as 3.1·109/l), and enlarged peripheral lymph nodes during her visit to a doctor. The bone marrow (BM) showed the changes typically encountered in myeloproliferative disease with eosinophilia. The patient was found to have t(8;13)(p11;q12) translocation associated with the rearrangement of the FGFR1 gene located at the 8p11 locus. Molecular and cytogenetic examinations failed to reveal BCR-ABL chimeric transcript, Jak2 V617F mutation, and deletions and translocations involving PDGFRA (4q12) and PDGFRB (5q32-33). The similar changes in the karyotype were also found in the lymph node cells. The undertaken treatment with hydroxyurea and the tyrosine kinase inhibitor dasatinib turned out to be ineffective. The patient underwent allogeneic BM transplantation from a HLA-identical sibling. Graft rejection occurred 6 months later. Allogeneic BM transplantation from the same donor (100% donor chimerism; FGFR1/8Ñ11 translocation was not detected), which was complicated by the development of chronic graft-versus-host reaction, was performed again in March 2015. The patient is being followed up and continues to receive immunosuppressive therapy.
Assuntos
Eosinofilia , Leucocitose , Linfadenopatia , Transtornos Mieloproliferativos , Adulto , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 8/genética , Eosinofilia/complicações , Eosinofilia/diagnóstico , Eosinofilia/genética , Eosinofilia/terapia , Feminino , Humanos , Leucocitose/diagnóstico , Leucocitose/etiologia , Leucocitose/genética , Leucocitose/terapia , Linfadenopatia/diagnóstico , Linfadenopatia/etiologia , Linfadenopatia/genética , Linfadenopatia/terapia , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/terapia , Translocação GenéticaRESUMO
AIM: To evaluate the effect of pathogen-inactivated platelet concentrates (PIPC) on posttransfusion platelet increments, hemorrhagic syndrome relief, and transfusion intervals. SUBJECTS AND METHODS: This prospective study included 29 hemoblastosis patients (13 women, 16 men), median age 38 years (20-66 years). Pathogens were inactivated by the photodynamic method using the Intecept system. Each patient received two PC transfusions: one PIPC transfusion and one control one. Posttransfusion platelet increments one hour and one day after PC transfusion, the course of hemorrhagic syndrome, and the time to next platelet transfusion were analyzed. RESULTS: Pathogen inactivation with amotosalen and ultraviolet irradiation reduced posttransfusion platelet increments in recipients by 24% after one hour and by 29% after one day after PIPC transfusion versus control ones. CONCLUSION: The clinical efficiency of transfusions of amotosalen-induced PIPC was comparable with that of untreated platelet concentrates. Despite a reduction in post-transfusion platelet increment with the use of PIPC, this caused no significant increase in the frequency of transfusions.
Assuntos
Furocumarinas/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Transfusão de Plaquetas/métodos , Trombocitopenia/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia/instrumentação , Transfusão de Plaquetas/instrumentação , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To make differential diagnosis of thymic hyperplasia and mediastinal tumor after chemotherapy (CT) in patients with Hodgkin's disease (HD). MATERIAL AND METHODS: The examination of 182 HD patients aged 16-71 years (median 28 years) included chest x-ray computed tomography (XCT) at baseline, during treatment, each 3 months, ultrasound investigation of the chest and abdominal cavity. All the patients received 6-8 courses of the treatment according to the program BEACOPP-14 followed by radiotherapy on the residual tumor in 137 patients, or not followed in 45patients. RESULTS: Soft tissue tumor in the anterior mediastinum was detected in 14 (31%) from 45 unirradiated patients (age 19-31 years, median 24 years) 1 to 10 months (median 3.5 months) after chemotherapy. The analysis of the data of ultrasound investigation and tomography identified a mediastinal lesion as thymic hyperplasia. The patients are now in remission with follow-up median 21 months (13-36 months). No recurrence was registered. CONCLUSION: Young HD patients with unirradiated mediastinum develop thymic hyperplasia in 31% cases within one year after chemotherapy. In view of this, detection of the lesion in the anterior mediastinum after CT demands complex examination for differential diagnosis of thymic hyperplasia with tumor recurrence to avoid unwanted intensification of the treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Neoplasias do Mediastino/diagnóstico , Hiperplasia do Timo/diagnóstico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Diagnóstico Diferencial , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/complicações , Humanos , Masculino , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/etiologia , Pessoa de Meia-Idade , Radiografia , Hiperplasia do Timo/diagnóstico por imagem , Hiperplasia do Timo/etiologia , Ultrassonografia , Adulto JovemRESUMO
AIM: To study prognostic factors in previously untreated patients receiving FC regimen (fludarabine plus cyclophosphamide). MATERIAL AND METHODS: We conducted a retrospective analysis of B-CLL patients observed in Hematology Research Center of Russia (Moscow) and Faculty Therapy Clinic of St. Petersburg State Medical University (St. Petersburg). All patients received FC regimen as a first line treatment (fludarabine 50 mg plus cyclophosphamide 250 mg/m2 for 3 days intravenously, repeated every 28 days). RESULTS: 54 patients were included into the study. The median age was 57.5 yrs (range 40-78 yrs). There were 38 males and 16 females. Before the treatment 22% patients had Binet stage A, 41%--stage B and 37%--stage C. 62% patients had unmutated subtype of B-CLL and 38% mutated subtype. 12 patients (22%) received less than 4 cycles of chemotherapy. In 8 patients (15%) there were significant delays between cycles (more than 2 months). In the whole cohort the median overall survival calculated from the time of treatment initiation was 57.4 months, the median progression free survival--24 months, and the median relapse free survival--27 moths. Mutational status of immunoglobulin variable region genes significantly influenced survival. In patients with unmutated subtype the median progression free survival was 23.6 months, while in patients with mutated subset it was not reached: 75% survival at 22.7 months (p = 0.027). Difference in progression free survival by stages (A versus B+C, A+B versus C) was not significant. CONCLUSION: Our data show that mutational status of immunoglobulin variable region genes remains a significant prognostic factor in patients receiving combined therapy with cyclophosphamide and fludarabine.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
AIM: To study possibilities of cure of hemoblastosis patients in the setting of day hospital (DH). MATERIAL AND METHODS: The experience with 5-year activity of the first in Russia hematological DH is analyzed. Managerial, clinical, economic and social aspects of DH activity are considered. RESULTS: Basing on the experience of the DH activity, indications for hospitalization of patients with hematological malignancy (HM) to DH, the model of management of hematological DH, the diseases which can be treated in hematological DH are specified. Cost-effect efficacy of establishment of hematological day hospitals is validated. CONCLUSION: Hematological DH is a modern, cost effective form of rendering special medical assistance in outpatient setting providing examination and treatment of hematological patients without loss of quality of diagnosis, treatment and life.
Assuntos
Assistência Ambulatorial/métodos , Hematologia/métodos , Ambulatório Hospitalar , Assistência Ambulatorial/economia , Análise Custo-Benefício , Neoplasias Hematológicas/terapia , Hematologia/economia , Humanos , Ambulatório Hospitalar/economiaRESUMO
AIM: To analyse overall recurrence-free survival of lymphogranulomatosis (LGM) patients given polychemotherapy (PCT) MOPP (mustargen-caryolisin, vincristine, natulan, prednisolone) - ABVD (adriamycin, bleomycin, vinblastin, dacarbasin) in combination with radiotherapy (RT) for 10 years. MATERIAL AND METHODS: The trial included 211 LGM patients admitted to Hematological Research Center in 1990-1996 from other hospitals without random selection. The patients were examined by the standard program including biopsy of the affected organ or lymph node, bilateral trephine biopsy. Splenectomy was performed in 17 patients, 83 patients received PCT in other hospitals, 128 untreated patients received MOPP-ABVD therapy (3 courses of MOPP and 3 courses of ABVD). Forty one patients had defects in PCT, 16 of them rejected PCT and RT. The latter was performed 4 weeks after the 6th course, contraceptives were not prescribed to women. At LGM stage II-III RT was performed by the subradical program (no radiation to ilioinguinal lymph nodes) in doses 40-44 Gy on the foci and 32-36 Gy preventively, on massive and residual foci after PCT - 5-10 Gy additionally. RESULTS: Ten-year overall and recurrence-free survival in the untreated group reached 83 and 80%, respectively, for pretreated patients - 46 and 36%, respectively. Causes of death of 26 patients were LGM progression, infection (tuberculosis, as a rule), secondary tumors and acute myeloblastic leukemia (AML). After remission 25 women gave birth to a healthy child and 12 healthy children were born to 9 males. CONCLUSION: MOPP-ABVD plus radiotherapy program according to subradical and radical variants was in the past effective but invalidating rescue therapy. Present-day programs consider the histological variant, stage and prognostic factors allowing an individual therapeutic approach with step-by-step reduction of RT in the treatment of LGM patients. Involvement of the bone marrow in primary patients had no influence on the treatment results. This refers this affection not to a generalized stage IV, but to stage III along with involvement of the lymph nodes and the spleen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Idoso , Biópsia , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/patologia , Humanos , Masculino , Mecloretamina/administração & dosagem , Mecloretamina/uso terapêutico , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisona/uso terapêutico , Procarbazina/administração & dosagem , Procarbazina/uso terapêutico , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vincristina/administração & dosagem , Vincristina/uso terapêuticoRESUMO
The data on the myelogram, peripheral blood and the proteinogram of 30 donors infected with human immunodeficiency virus are provided. The donors were observed for 6 months in the Department of Hematology and Blood Transfusion of the Mukhimbili hospital (Dar-es-Salaam, Tanzania). It is concluded that the above-enumerated parameters should be controlled over time, which is likely to be instrumental in the diagnosis of a qualitatively new condition of the patients--a stage of human immunodeficiency infection transformation to AIDS.
Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Doadores de Sangue , Síndrome da Imunodeficiência Adquirida/sangue , Adulto , Proteínas Sanguíneas/análise , Exame de Medula Óssea , Anticorpos Anti-HIV/análise , Soropositividade para HIV/sangue , Soropositividade para HIV/diagnóstico , Humanos , Masculino , TanzâniaRESUMO
AIM: To investigate whether plasma replacement (PR) can raise efficiency of drug therapy of ischemic heart disease (IHD). MATERIAL AND METHODS: A 30-60% replacement of circulating plasma for salt or dextran using PF-05 unit has been performed in 324 patients 35-79 years of age with recurrent myocardial infarction and angina pectoris. A total of 520 PR procedures were performed. Biochemical, acid-base, coagulative, viscosity, microcirculatory blood parameters were taken, ECG and stress tests were made. RESULTS: PR resulted in a significant reduction in packed cell volume, total protein, fibrinogen, low density lipoproteins, total cholesterol and led to diminution of blood viscosity, acceleration of capillary blood flow, improvement of O2/CO2. Lowering of fibrinogen levels, number of platelets and their aggregation, enhancement of fibrinolytic blood activity created conditions for moderate controlled hypocoagulation. As shown by stress tests, two weeks after PR 60% of anginal patients of functional class IV can be transferred to class III. CONCLUSION: Because PR is beneficial by many parameters, it lessens the requirement in pharmacological support of patients with complicated IHD.
Assuntos
Angina Pectoris/terapia , Dextranos , Infarto do Miocárdio/terapia , Substitutos do Plasma , Adulto , Idoso , Angina Pectoris/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangueRESUMO
A total of 142 patients with anemias diagnosed at the Mukhimbili Hospital (Tanzania) were investigated on the basis of the analysis of the peripheral blood and marrow puncture.
Assuntos
Anemia/diagnóstico , Humanos , TanzâniaRESUMO
Analysis of the characteristic changes in the activity of the tetrade of lymphocyte dehydrogenases (malate, lactate, succinate and mitochondrial alpha-glycerophosphate dehydrogenase) in patients suffering from chronic lymphoid leukemia is regarded by the authors of the paper as one of the sources of information permitting one to forecast the course of the disease under study.
Assuntos
Leucemia Linfocítica Crônica de Células B/sangue , Linfócitos/enzimologia , Oxirredutases/sangue , Adulto , Idoso , Glicerolfosfato Desidrogenase/sangue , Humanos , L-Lactato Desidrogenase/sangue , Malato Desidrogenase/sangue , Pessoa de Meia-Idade , Prognóstico , Succinato Desidrogenase/sangueRESUMO
The time of NMR-spin-lattice relaxation of 65 serum samples from acute leukemia patients and those with chronic myelo- and lymphoproliferative diseases was measured. The patients studied demonstrated greater values of the parameter which proved dissimilar at various stages of the disease in the same patients.
Assuntos
Doenças Hematológicas/sangue , Espectroscopia de Ressonância Magnética/métodos , HumanosRESUMO
Iron metabolites were measured in liver homogenates and leukocytes of patients with hereditary hemochromatosis (HHC), chronic viral hepatitis, and secondary iron overloading. Iron and ferritin levels in the liver are increased HHC, while in hepatitis only ferritin level is increased. In the leukocytes ferritin concentrations are increased both in HHC and secondary iron loading and less so in viral hepatitis. The leukocytic ferritin level decreased after a course of bleeding sessions and during maintenance therapy for HHC, which can serve as a diagnostically significant sign for evaluating the treatment efficiency.