RESUMO
The introduction of tyrosine kinase inhibitors (TKI) in the treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) has revolutionized the outcome, but the prognosis of the disease is still based on prognostic systems that were developed in the era of conventional chemotherapy and interferon (IFN)-alfa. A new prognostic score including only two variables, spleen size and basophils, was developed for the prediction of complete cytogenetic response (CCyR) and progression-free survival (PFS). The score was based on a large series of patients who were enrolled in prospective multicenter studies of first-line imatinib treatment. The prognostic value of the EUTOS (European Treatment and Outcome Study for CML) score has now been tested in an independent, multicenter, multinational series of 1288 patients who were treated first-line with imatinib outside prospective studies. It was found that also in these patients, the EUTOS prognostic score was predictive for CCyR, PFS and overall survival (OS). In addition, the prognostic value of the score was reported to be significant in seven of the eight other independent studies of almost 2000 patients that were performed in Europe, the Americas and Asia. The EUTOS risk score is a valid tool for the prediction of the therapeutic effects of TKI, particularly imatinib.
Assuntos
Benzamidas/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Proteínas Tirosina Quinases/antagonistas & inibidores , Taxa de Sobrevida , Estudos de Validação como Assunto , Adulto JovemAssuntos
Transplante de Medula Óssea/métodos , Síndrome Hipereosinofílica/terapia , Proteínas de Fusão Oncogênica/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética , Adulto , Seguimentos , Humanos , Masculino , RNA Mensageiro/análise , Transplante HomólogoRESUMO
Imatinib mesylate is a very effective treatment in patients with Philadelphia (Ph)-positive chronic myeloid leukaemia (CML). However, in patients with advanced phase CML, it is still unclear whether, in the presence of myelosuppression, therapy with imatinib should be continued. It has been reported that intermittent filgrastim treatment may overcome imatinib-associated neutropenia and allow improved delivery of imatinib. Such combined sequential treatment is theoretically attractive as it may lead to better disease response. Here, we report a patient with blastic phase CML who developed severe and prolonged myelosuppression during imatinib treatment. Despite cessation of imatinib and 2 months of filgrastim therapy neither recurrence of Ph-positive or Ph-negative cells occurred. We conclude that filgrastim treatment may not always reverse imatinib-associated neutropenia therefore the decision of continued imatinib therapy in patients with advanced CML should be taken with caution.
Assuntos
Antineoplásicos/efeitos adversos , Crise Blástica/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Neutropenia/tratamento farmacológico , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , Benzamidas , Feminino , Filgrastim , Humanos , Mesilato de Imatinib , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Proteínas RecombinantesRESUMO
It is unknown whether imatinib prior to myeloablative haematopoietic stem cell transplantation (HSCT) increases transplant-related toxicity. Among the side effects induced by imatinib, myelosuppression and liver injury might worsen HSCT outcomes. We retrospectively analysed engraftment, liver toxicity, acute graft-versus-host disease (aGVHD) incidence and 100-day mortality in 30 patients with BCR/ABL-positive leukaemias who received imatinib before HSCT and compared results of 48 age-matched controls who did not receive preceding imatinib. Both neutrophil and platelet engraftment occurred more rapidly among imatinib patients but the differences adjusted for Gratwohl scale were not statistically significant (P = 0.18 and 0.22, respectively). The adjusted hazards of having liver function tests (LFTs) >1.5 normal increased and the adjusted durations of elevated LFTs were not significantly different. The estimated adjusted difference in mean peak bilirubin values was also not significantly different (P = 0.48). However, the adjusted hazard of increased creatinine >1.5 normal was significantly higher in the imatinib group (HR = 4.09, P = 0.02). The adjusted odds of grades II-IV aGVHD were similar in both groups (OR = 0.86, P = 0.78), and while the adjusted odds of 100-day mortality were lower among imatinib patients, the difference was not significant (OR = 0.65, P = 0.60). These data do not provide any evidence that imatinib preceding HSCT increases acute transplant-related toxicities.
Assuntos
Antineoplásicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Transplante Homólogo , Adolescente , Adulto , Benzamidas , Bilirrubina/sangue , Plaquetas/metabolismo , Creatinina/sangue , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Quimeras de Transplante , Condicionamento Pré-Transplante/métodosRESUMO
STI571 shows clinical activity in the treatment of chronic myelogenous leukemia, Philadelphia positive acute lymphoblastic leukemia and gastrointestinal stromal tumors. Resistance of normal progenitor cells to STI571 is essential when determining the optimal therapeutic window for patients with cancer without bone marrow involvement, and for patients with chronic myeloid leukemia who achieved complete cytogenetic remission. The effect of graded concentrations of STI571 on the clonogenic potential of normal fresh bone marrow hematopoetic progenitor cells from 13 normal individuals was analyzed. It was shown that lower concentrations of STI571 (0.1 and 0.5 microM/l) may increase colony numbers, whereas higher concentrations (>1 microM/l) may reduce normal colony formation.
Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Células-Tronco Hematopoéticas/citologia , Piperazinas/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/farmacologia , Benzamidas , Ensaio de Unidades Formadoras de Colônias , Humanos , Mesilato de Imatinib , Púrpura Trombocitopênica Idiopática/enzimologiaRESUMO
Large Granular Lymphocyte (LGL) Leukaemia is uncommon proliferative disorder of LGL lymphocytes. Classification, clinical features and treatment of LGL leukaemia are described.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Linfoide/tratamento farmacológico , Leucemia Linfoide/etiologia , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/etiologia , Tumores de Células GigantesRESUMO
PCR amplification of highly polymorphic variable number of tandem repeat (VNTR) sequences could be particularly useful in documentation of engraftment and characterization of chimerism following allogeneic bone marrow transplantation (BMT). We have monitored a 31-year old male patient treated with allogeneic BMT for chronic myeloid leukaemia. The recipient's DNA samples were obtained before the transplant and on day 28, 100 and 150 after BMT. The donor's DNA (patient's sister) was also obtained as a reference. ACT B2 locus on chromosome 6 was chosen for the analysis. In addition a deletion polymorphism locus within the pseudoautosomal region of chromosome X and Y (amelogenin gene) was also analysed. On day 28 after BMT both donor and recipient specific alleles were detected in the recipient's sample. However, on day 100 and 150 the recipient specific alleles were no longer detectable. The aforementioned pattern was observed for both markers analysed. The disappearance of recipient specific alleles correlated with clinical symptoms of chronic graft-versus host disease.
Assuntos
Transplante de Medula Óssea/fisiologia , Adulto , Sequência de Bases , Cromossomos Humanos Par 6/genética , DNA/análise , Feminino , Marcadores Genéticos , Doença Enxerto-Hospedeiro/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/cirurgia , Masculino , Repetições Minissatélites , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Quimeras de Transplante/genética , Cromossomo X/genética , Cromossomo Y/genéticaRESUMO
Retrospective estimate was performed of the results of treatment of 67 patients aged from 18 to 80 years with diagnosed idiopathic thrombocytopenia, treated in the Haematological Outpatient Clinic in the years 1980-1992. In the treatment adrenocortical hormones (prednisone) were used in dose 1 mg/kg body weight daily for at least six weeks, and in cases refractory to treatment or disease recurrence the patients were referred for splenectomy or cytostatic immunosuppression was used. In highest per cent permanent remissions were achieved in the patients subjected to splenectomy as compared with other methods of treatment.