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1.
Leukemia ; 31(7): 1525-1531, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28218239

RESUMO

The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR4.5 (BCR-ABL1⩽0.0032% on the International Scale (BCR-ABL1IS)) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1IS⩽0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2-58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR4.5 by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/psicologia , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Qualidade de Vida
2.
Leukemia ; 30(9): 1853-60, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27133821

RESUMO

Dasatinib (DAS) and interferon-α have antileukemic and immunostimulatory effects and induce deep responses in chronic myeloid leukemia (CML). We assigned 40 newly diagnosed chronic-phase CML patients to receive DAS 100 mg o.d. followed by addition of pegylated interferon-α2b (PegIFN) after 3 months (M3). The starting dose of PegIFN was 15 µg/week and it increased to 25 µg/week at M6 until M15. The combination was well tolerated with manageable toxicity. Of the patients, 84% remained on PegIFN at M12 and 91% (DAS) and 73% (PegIFN) of assigned dose was given. Only one patient had a pleural effusion during first year, and three more during the second year. After introduction of PegIFN we observed a steep increase in response rates. Major molecular response was achieved in 10%, 57%, 84% and 89% of patients at M3, M6, M12 and M18, respectively. At M12, MR(4) was achieved by 46% and MR(4.5) by 27% of patients. No patients progressed to advanced phase. In conclusion, the combination treatment appeared safe with very promising efficacy. A randomized comparison of DAS±PegIFN is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Dasatinibe/administração & dosagem , Interferon-alfa/administração & dosagem , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Derrame Pleural , Proteínas Recombinantes/administração & dosagem , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
3.
Leukemia ; 8(9): 1585-8, 1994 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8090035

RESUMO

All-trans retinoic acid (ATRA) was used in a case of acute promyelocytic leukemia (APL) in late pregnancy. A very prompt maternal risk reduction was achieved with subsequent complete remission and spontaneous delivery of two live children in whom no fetal damage seems to have occurred.


Assuntos
Leucemia Promielocítica Aguda/tratamento farmacológico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Tretinoína/uso terapêutico , Adulto , Feminino , Fibrinogênio/metabolismo , Hemoglobinas/metabolismo , Humanos , Leucemia Promielocítica Aguda/sangue , Contagem de Leucócitos , Contagem de Plaquetas , Gravidez , Complicações Neoplásicas na Gravidez/sangue , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Indução de Remissão , Tempo de Trombina
4.
Leukemia ; 8 Suppl 2: S77-80, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7815844

RESUMO

All-trans retinoic acid (ATRA) was used in a case of acute promyelocytic leukemia (APL) in late pregnancy. A very prompt maternal risk reduction was achieved with subsequent complete remission and spontaneous delivery of two live children in whom no fetal damage seems to have occurred.


Assuntos
Leucemia Promielocítica Aguda/tratamento farmacológico , Complicações Neoplásicas na Gravidez/tratamento farmacológico , Tretinoína/uso terapêutico , Adulto , Feminino , Humanos , Leucemia Promielocítica Aguda/complicações , Gravidez , Indução de Remissão
5.
Neoplasia ; 1(6): 492-7, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10935496

RESUMO

We have investigated a single telomere expansion in a case of acute lymphoblastic B-cell leukemia (B-ALL), where half of the cells in the bone marrow sample appeared with a Philadelphia chromosome. Comparing telomere sizes in Philadelphia-positive versus -negative cells, we found generally shorter telomeres in the Philadelphia-positive cells, but with an expansion of the telomere on the long arm of one chromosome 11 homologue. This expansion was also found in a minority of Philadelphia-negative cells. The telomeres in these cells were of the same overall size as the telomeres in the Philadelphia-negative cells without the 11q expansion. Together, these findings suggest that the order of events was: 11q telomere expansion, Philadelphia translocation, overall telomere shortening. The expanded 11q telomere contained the standard telomeric (AGGGTT)(n) repeat, but also variant repeat sequences. The single telomere expansion suggests a non-telomerase mechanism behind the expansion which may also explain the presence of variant repeats in the expanded telomere. The present case illustrates that telomere changes may occur at only some chromosome ends in a subset of cells. To reveal such changes, telomere morphology should be studied with in situ methodology.


Assuntos
Linfoma de Burkitt/genética , Cromossomo Filadélfia , Telômero , Adulto , Cromossomos Humanos Par 11 , Humanos , Masculino , Sequências Repetitivas de Ácido Nucleico
6.
Drug Saf ; 5(1): 7-27, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2178634

RESUMO

The principal toxicity of standard induction regimens for acute non-lymphocytic leukemia (ANLL) [including cytarabine (ARA-C) 100 mg/m2 for 7 days plus an anthracycline] is myelotoxicity, leading to death in at least 25% of cases during induction in non-selected patients. The complete remission rate is less than 35% in patients over 65 years of age, due in part to an age-related increase of myelotoxicity. The other important adverse effect of standard-dose cytarabine is gastrointestinal toxicity, especially oral mucositis, diarrhoea, intestinal ulceration, ileus and subsequent Gram-negative septicaemia. Idiosyncratic reactions like exanthema, fever and elevation of hepatic enzymes are relatively frequent, but do not represent therapeutic problems. Intermittent high-dose cytarabine (3 g/m2 in 8 to 12 doses) is extremely myelosuppressive. Similarly, the gastrointestinal toxicity is formidable and dose-limiting. Severe, and sometimes irreversible, cerebellar/cerebral toxicity in 5 to 15% of courses of treatment limits the peak dose of cytarabine. The pathogenesis, prophylactic and therapeutic measures are unknown. These major toxicities are age-related and prohibitive to the use of high-dose cytarabine therapy in patients older than 55 to 60 years. Subacute noncardiogenic pulmonary oedema occurs in some patients, with an incidence of about 20%, and seems to have an intriguing coincidence with precedent streptococcal septicaemia; high-dose systemic steroids may be beneficial. Corneal toxicity is very frequent in high-dose cytarabine therapy but is always reversible. It is largely preventable with prophylactic steroid or 2-deoxycytidine eyedrops. Fever, exanthema and hepatic toxicity have an incidence similar to that in standard dosage. The maximum tolerable cumulated dose of cytarabine is significantly lower when the agent is administered as a continuous infusion, due to myelosuppression and gastrointestinal toxicity. Conversely, continuous infusion may be less neurotoxic. The antileukaemic effect of continuous infusion high-dose cytarabine is less well established. The only significant toxicity of low-dose cytarabine is myelosuppression. Given the generally poor condition of leukaemia patients, low-dose cytarabine therapy is well tolerated, although occasional cases of diarrhoea, reversible cerebellar symptoms, peritoneal and pericardial reactions, and ocular toxicity have been reported. Continuous infusion may be more toxic than the usual intermittent dosage. It is concluded that the toxicity of the standard induction regimen for ANLL is acceptable in patients younger than 60 to 65 years with no concurrent disease. Low dose cytarabine is tolerable for virtually all ANLL patients, but the overall therapeutic efficacy still needs to be defined and compared to standard therapy in the relevant age groups.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Citarabina/toxicidade , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade
7.
Ugeskr Laeger ; 156(43): 6380-4, 1994 Oct 24.
Artigo em Dinamarquês | MEDLINE | ID: mdl-7810014

RESUMO

We report the outcome of 95 patients older than 60 years with de novo acute non-lymphocytic leukaemia (ANLL), treated in two institutions during a 10 year period. Thirty-two patients, mean age 78 years, did not receive any chemotherapy, and their median survival was 38 days. Five patients in good clinical condition, aged 60-63 years, were treated conventionally with an anthracycline and cytarabine, and three patients obtained a complete remission (CR) lasting 73, 417, and 1050 days. Fifty-eight patients were treated with low-dose cytarabine (LDC) for remission-induction and maintenance. Eighteen patients obtained CR, yielding a remission rate of 31%. The median duration of remission was 380 days and median survival of the same group was 498 days. LDC is valuable in the treatment of ANLL in the elderly. Controlled studies are warranted to define the indications for LDC versus conventional therapy in the large grey zone of elderly patients.


Assuntos
Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Fatores Etários , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Acta Med Scand ; 221(4): 403-7, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3604756

RESUMO

A 26-year-old woman with extra-pulmonary Wegener's granulomatosis was treated with cyclophosphamide for 3.25 years, cumulated dose of 91 g. Six months before cessation of therapy discrete radiological signs of apical fibrosis appeared. The changes were progressive regardless of discontinuation of cyclophosphamide and led to severe restrictive ventilatory defect.


Assuntos
Ciclofosfamida/efeitos adversos , Fibrose Pulmonar/induzido quimicamente , Adulto , Feminino , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Fibrose Pulmonar/diagnóstico por imagem , Radiografia
13.
Acta Haematol ; 76(2-3): 127-9, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3101350

RESUMO

Low-dose cytosine arabinoside (ARA-C) induced complete remissions in 6 of 10 patients with acute non-lymphocytic leukaemia (ANLL) who were either refractory to combination chemotherapy with anthracyclines and conventional doses of ARA-C, or were in relapse. Three patients relapsed after 4, 19, and 20 months, whereas 3 patients are still in remission for 8-46 months. Low-dose ARA-C was rather non-toxic and may be preferable to more intensive and toxic regimens in the therapy of refractory and relapsing patients with ANLL.


Assuntos
Citarabina/administração & dosagem , Leucemia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Relação Dose-Resposta a Droga , Humanos
14.
Eur J Haematol ; 38(3): 284-7, 1987 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-3595815

RESUMO

5 heavily pretreated patients with chronic lymphocytic leukaemia or non-Hodgkin lymphoma resistant to alkylating agents were treated with low-dose cytosine arabinoside (ARA-C). 3 of the patients showed a clinical and laboratory improvement lasting from 8 to more than 20 months. Low dose ARA-C may be therapeutically effective in terminal stages of lymphoproliferative disorders.


Assuntos
Citarabina/uso terapêutico , Leucemia Linfoide/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Medula Óssea/patologia , Feminino , Humanos , Leucemia Linfoide/patologia , Contagem de Leucócitos/efeitos dos fármacos , Linfócitos/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade
15.
Scand J Haematol ; 37(1): 59-62, 1986 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-3094133

RESUMO

The concentration of xanthine and hypoxanthine was measured in 8 portions of SAGM red cell concentrates during 4 wk storage. The concentration of xanthine increased from 4.2 to 35.1 mumol/l and the concentration of hypoxanthine increased from 16.8 to 165.2 mumol/l (mean values). Previous studies have demonstrated several important effects of purine bases--among these a reduced cytotoxicity of purine antimetabolites. It is concluded that further studies are necessary to investigate the clinical role of purines in stored blood products.


Assuntos
Adenina , Preservação de Sangue , Glucose , Hipoxantinas/sangue , Manitol , Cloreto de Sódio , Xantinas/sangue , Humanos , Hipoxantina , Fatores de Tempo , Xantina
16.
Scand J Thorac Cardiovasc Surg ; 22(2): 189-91, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-3261452

RESUMO

In a 51-year-old man, coronary artery bypass surgery for severe angina pectoris was followed by protracted mediastinal infection. After recovery the patient had several haemoptyses. Angiography revealed aneurysm of a graft near its distal anastomosis. Upper left lobectomy and ligation of the graft were necessitated by bleeding from the aneurysm into a segmental bronchus. Angina pectoris recurred but was successfully treated with verapamil.


Assuntos
Dissecção Aórtica/etiologia , Ponte de Artéria Coronária , Hemoptise/etiologia , Complicações Pós-Operatórias/etiologia , Veia Safena/transplante , Humanos , Masculino , Pessoa de Meia-Idade
17.
Lancet ; 359(9319): 1751-2, 2002 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-12049868

RESUMO

Imatinib is a potent drug used in treatment of chronic myeloid leukaemia (CML). It acts by inhibition of the CML-specific p210 BCR-ABL tyrosine kinase, but also blocks other pathways such as platelet-derived growth factor (PDGF) and c-kit receptor signalling. Clinical trials have confirmed the efficacy of imatinib, which has toxic effects in cells that express BCR-ABL. Side-effects, although frequent, are generally mild and include superficial oedema and fluid retention. Here, we describe two patients with cerebral oedema, which in one patient was fatal. The pathophysiological mechanisms remain unknown, although the drug could act through inhibition of the PDGF receptor.


Assuntos
Edema Encefálico/induzido quimicamente , Inibidores Enzimáticos/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/efeitos adversos , Pirimidinas/efeitos adversos , Idoso , Benzamidas , Edema Encefálico/diagnóstico por imagem , Edema Encefálico/patologia , Evolução Fatal , Feminino , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
18.
Eur J Haematol ; 67(5-6): 302-8, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11872078

RESUMO

The activated tyrosine kinase, which arises as a result of the balanced t(9,22) translocation in chronic myeloid leukemia (CML), is thought to be essential for the development of the leukemic phenotype. Recently, designer drugs have been introduced which specifically inhibit such specific kinases. Among these, STI571 (Glivec) has entered clinical trials and shown promising activities in chronic phase (CP), accelerated phase (AP) and blast crisis (BC) as evidenced by significant hematological and cytogenetic responses in CML patients. To evaluate the effect of STI571 at the molecular level we have employed quantitative real-time PCR (RQ-PCR) to measure the amount of BCR-ABL fusion transcript in a series of 19 patients treated with STI571, either in CP(11) or in (AP)(8) of the disease for 3--9 months (median 6 months). Employing this method, which is able to detect at least one BCR-ABL+ cell in 500,000, in serial blood and bone marrow specimens we found decreases in transcript levels in 10/11 CP patients, but only in 1/8 of the AP patients. When present such decreases were gradual and became evident only after 3 months of STI571 treatment, and their kinetics in blood closely mirrored those seen in parallel marrow samples. Moreover, decreases were between 10- and 100-fold in 11/13 patients, with only two patients reaching residual disease levels below 10(-2) (a 900-fold decrease). Thus, no patient reached PCR negativity. We conclude that the RQ-PCR method is a highly suitable tool for following the effect of STI571 in CML and that further validation of the method, performed in a prospective manner, will contribute significantly to the elucidation of the proper role of STI571 in CML.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Benzamidas , Biomarcadores Tumorais , Feminino , Proteínas de Fusão bcr-abl/sangue , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/antagonistas & inibidores , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e Especificidade , Transcrição Gênica
19.
Eur J Haematol ; 52(4): 236-9, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8005235

RESUMO

Thirteen patients with de novo acute non-lymphocytic leukaemia (ANLL) refractory to standard chemotherapy for remission induction and 12 patients with ANLL in relapse were treated with low-dose cytosine arabinoside (LD ara-C) 10 mg/m2 subcutaneously every 12 hours for 21 days. Five of 13 patients (38%) and 6 of 12 patients (50%), respectively, obtained a complete remission (CR). Of these, 7 patients subsequently relapsed after 2-76 months, while 4 patients remain in CR after 7-131 months. Compared to standard intensive regimens treatment with LD ara-C was rather non-toxic, requiring platelet transfusions and antibiotics in only 6 and 13 cases, respectively. Three patients (12%) died during induction therapy with LD ara-C; 2 had a cerebral haemorrhage and 1 developed anuria following a staphylococcal septicaemia. In conclusion, therapy with LD ara-C may be preferable to more intensive and toxic regimens in the treatment of patients with relapsed or refractory ANLL.


Assuntos
Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Acta Obstet Gynecol Scand ; 71(8): 605-9, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1336919

RESUMO

Lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) have been reported to be associated with fetal loss. OBJECTIVE. Our aim was to estimate the incidence of LA and to examine the correlation between LA and ACA in pregnant women. To investigate the clinical significance of LA and ACA in an obstetric population. STUDY DESIGN. A prospective, cross sectional study of 2856 consecutive women admitted to a department of obstetrics and gynecology for delivery or due to pregnancy complications during an 11 month period. METHODS. Activated partial thromboplastin time (APTT) was determined in all patients. LA and ACA were determined if APTT > or = 35 sec. For reference ACA was determined in a group of randomly selected patients with APTT < 35 sec. The results were analyzed in relation to the obstetrical records. RESULTS. Overall incidence of APTT > or = 35 sec.: 7.0%, significantly more frequent in patients with early spontaneous abortion (18.6%) and intrauterine growth retardation (17.5%). Incidence of LA 0.07%. The patients had undetectable ACA and no clinical condition related to LA. Incidence of ACA class IgM (IgM-ACA) in patients with APTT > or = 35: 20.4%, significantly higher than in the reference group (9.6%). Uncomplicated pregnancy in 84% of patients with IgM-ACA. No cases of ACA class IgG (IgG-ACA) in patients with APTT > or = 35 but two cases in the reference group (one normal pregnancy, one spontaneous abortion). CONCLUSION. LA is a rare manifestation with uncertain significance in otherwise healthy pregnant women. IgM-ACA in low titer occurs relatively frequently during normal pregnancy.


Assuntos
Anticorpos Anticardiolipina/sangue , Inibidor de Coagulação do Lúpus/sangue , Gravidez/imunologia , Adolescente , Adulto , Anticorpos Anticardiolipina/imunologia , Estudos Transversais , Feminino , Humanos , Imunoglobulina M/análise , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Gravidez/sangue , Complicações na Gravidez/sangue , Complicações na Gravidez/imunologia , Resultado da Gravidez , Estudos Prospectivos
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