RESUMO
The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has been shown to be active on acute myeloid leukemia (AML) and refractory anemia with excess of blasts (RAEB). Thirty-one elderly AML/RAEB patients (AML n=25; RAEB n=6) with a high rate of comorbidity were entered in a phase II study with low-dose cytarabine (Ara-C) and VPA. Fitness was evaluated by means of the Comprehensive Geriatric Assessment (CGA), including the Cumulative Illness Rating Scale (CIRS) score, the self-sufficiency scores of Activity of Daily Living (ADL) and Instrumental Activity of Daily Living (IADL). Eight patients obtained a lasting complete remission and 3 other patients obtained hematologic improvement for a total response rate of 35%. Five of 11 responding patients were relapsed or resistant after a previous treatment with Ara-C. Seven of 11 responding patients were assessed as frail at enrollment and/or had IADL impairment. Grades 3 and 4 toxicities were mainly hematological. Low-dose Ara-C and VPA is a relatively non-toxic combination with good therapeutic activity in elderly patients with AML/RAEB. This therapeutic approach represents an alternative treatment for patients who cannot undergo standard induction therapy.
Assuntos
Anemia Refratária com Excesso de Blastos/tratamento farmacológico , Citarabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Ácido Valproico/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anemia Refratária com Excesso de Blastos/genética , Anemia Refratária com Excesso de Blastos/patologia , Anticonvulsivantes/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Indução de Remissão , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Attempts to increase dose intensity have been hampered by hematologic toxicity. To address this issue, we designed a study to determine whether the reinfusion of PBPC significantly reduces the toxicity of multicyclic dose-intensive chemotherapy. Thirty refractory patients, median age 63, received CY 3 g/m2 plus melphalan 60 mg/m2 followed by PBPC and G-CSF (CM regimen). CY (at day 0) and G-CSF were used to mobilize PBPC harvested by a single leukapheresis at day 10. Melphalan was infused at day 11. PBPC were kept unprocessed at 4 degrees C for 48 h and reinfused at day 12. This regimen was repeated three times every 6 months. Outcomes were compared with those of 30 similar patients treated with melphalan 30 mg/m2 followed by G-CSF only, and repeated every 2 months for a total of six cycles. In patients receiving CY plus melphalan followed by PBPC reinfusion, the median duration of neutropenia (ANC < 500/microliters) and thrombocytopenia (platelets < 2500 microliters) was only 5 and 2 days respectively, and did not increase after the subsequent courses. Hematologic toxicity was quite similar to that observed after melphalan 30 mg/m2 plus G-CSF. The CM regimen was followed by 30% complete remission and 86% response > 50%, melphalan 30 mg/m2 by no complete remissions and 38% response > 50%. Patients receiving CM regimen showed a longer progression-free survival (22 vs 10 months, P < 0.01). The dose intensity of melphalan can be doubled by reinfusing PBPC without increasing toxicity. The combination of CY and melphalan followed by PBPC improves response rate and outcome when compared to low-dose melphalan.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Humanos , Infusões Intravenosas , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-IdadeRESUMO
An in vitro synergism between different inducers of AML cell differentiation has been previously observed. Therefore, we treated 53 myelodysplastic (MDS) patients with a low dose combination of cis-retinoic acid (cRA, 20-40 mg/day) and 1,25 alpha (OH)2 cholecalciferol [(OH)2D3, 1-1.5 micrograms/day] +/- intermittent 6-thioguanine (30 mg/m2/day). The latter was reserved for patients with bone marrow (BM) blast excess (> or = 5%). The treatment was well tolerated, without major toxicity. Among 25 patients with BM blasts less than 5%, we observed one complete, eight partial and four minor responses (response rate 52%) with a median response duration of 8 months (2 +/- 24). Median survival, which did not correlate with response, is projected at 76 months. Thirty-one patients with BM blast excess (> or = 5%), including three of the previous group who progressed to refractory anemia with excess of blasts (RAEB), were treated with the three-drug protocol. One complete, 12 partial and six minor responses were obtained (response rate 61%) with a median response duration of 6 months (2-29+). A significant difference in survival (P < 0.005) was observed between the 19 responders (median 25 months) and the 12 non-responders (median 9 months). A reduction in the transfusion need was observed in 41% of the transfusion-dependent patients with blast excess and in 53% of those without blast excess. Therefore, combined differentiating therapy seems more effective than previously reported single agent treatments and should be considered for a larger randomized study to assess its actual impact on survival of MDS patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Crise Blástica , Transfusão de Sangue , Transplante de Medula Óssea , Colecalciferol/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Indução de Remissão , Análise de Sobrevida , Tioguanina/administração & dosagem , Tretinoína/administração & dosagemRESUMO
BACKGROUND: Hodgkin's disease (HD) after the age of 65 years is uncommon and there are no published data on chemotherapy regimens devised for elderly HD patients. PATIENTS AND METHODS: From 1990 to 1993, 25 elderly HD patients were treated with the CVP/CEB regimen: chlorambucil 6 mg/sqm p.o. days 1 through 7, vinblastine 6 mg/sqm i.v. on day 1, procarbazine 100 mg/sqm p.o. days 1 through 7, prednisone 30 mg/sqm p.o. days 1 through 7, cyclophosphamide 500 mg./sqm i.v. day 15, etoposide 70 mg/sqm i.v. day 15, bleomycin 10 mg/sqm i.v. day 15. Each course was repeated every 4 weeks. Stage I and II patients were treated with 3 courses followed by involved field radiotherapy, while more advanced stage patients received 6 courses and radiotherapy was limited to bulky areas. The results of the CVP/CEB regimen are retrospectively compared to those of 74 elderly patients treated between 1982 and 1989 and subdivided into the following 2 groups: 32 patients treated according to the same therapy used at that time in younger patients, and 42 patients given alternative low aggressivity or palliative treatment. RESULTS: CVP/CEB is a well-tolerated regimen, with only 1 (4%) toxic death and 2 (8%) protocol violations/interruptions. The CVP/CEB complete remission rate (73%) compares favorably with our previous groups of patients, mainly because of the lower toxic death rate. However, the CVP/CEB relapse-free survival rate is lower than that of patients treated with more aggressive conventional regimens (47% vs. 77%, p < 0.02). The CVP/CEB overall survival and event-free survival rates are 55% and 32%, respectively, and they are not statistically different from those of patients treated before 1990. CONCLUSIONS: CVP/CEB is a well-tolerated low toxicity regimen with a high CR rate. The relapse rate is high and event-free survival is comparable to that of patients treated conventionally. Our results suggest the need for individualized treatment criteria for older patients with HD.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Bleomicina/uso terapêutico , Carboplatina/uso terapêutico , Ciclofosfamida/uso terapêutico , Etoposídeo/uso terapêutico , Humanos , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
BACKGROUND: This study was aimed to investigate the effect of long-term treatment with high-protease pancreatic extract on the recurrent abdominal pain of patients with chronic pancreatitis. METHODS: Twenty-six patients with a firm diagnosis of chronic pancreatitis and a pattern of recurrent pain were recruited and randomly assigned to treatment with pancreatic extract (Pancrex-Duo capsules, each containing 34,375 USP units of protease in enteric-coated microspheres) or placebo, at a dose of four capsules four times daily, for 4 months. At the end of the first period patients were switched to the other medication for the next 4 months. Four patients did not complete the study because of unbearable recurring pain or inadequate compliance with treatment. The other 22 patients daily recorded the presence, intensity, and duration of pain and the consumption of analgesics, for 8 months. RESULTS: No difference was found when intraindividual records during placebo and extract treatment periods were compared. Conversely, in the second 4 months of follow-up, regardless of the treatment given in the first period, there was a significant reduction in the cumulative pain score (median, 95; range, 0-1005, versus 134; 0-972; p < 0.05), in the number of days (8; 0-132, versus 13; 0-126; p < 0.02) and hours (54; 0-680, versus 80; 0-602; p < 0.05) of pain, and in the analgesic consumption score (0; 0-22, versus 12; 0-44; p = 0.02). CONCLUSIONS: Chronic supplementation with pancreatic extract is not beneficial in the management of recurrent pain in patients with chronic pancreatitis.
Assuntos
Dor Abdominal/terapia , Extratos Pancreáticos/uso terapêutico , Pancreatite/complicações , Dor Abdominal/etiologia , Adulto , Idoso , Análise de Variância , Colecistocinina/sangue , Doença Crônica , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Extratos Pancreáticos/administração & dosagem , Pancreatite/sangue , Recidiva , Fatores de TempoRESUMO
The Authors reviewed the postmortem findings of 36,671 autopsies performed from 1929 to 1982 in the hospitals of Torino with emergency ward. Two hundred and sixty-five cases of Aortic Dissection (A.D.) were found, and studied in relation to their frequency by sex and age, pathology, and antemortem diagnosis. The main outcome of this survey was the increasing frequency of the lesion in the autopsy population during the last 36 years considered, from 1/759 necropsies in 1947-1952, to 1/52 in 1977-1982. These data are discussed in relation to the hypothesis of a possible actual increase of A.D..
Assuntos
Aneurisma Aórtico/epidemiologia , Dissecção Aórtica/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Dissecção Aórtica/patologia , Aneurisma Aórtico/patologia , Autopsia , Criança , Pré-Escolar , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
Liver biopsies were performed on 60 patients by means of percutaneous needle biopsy, and immediately after that procedure, during laparoscopy from the right and left liver lobes. The histological diagnoses obtained by examining the percutaneous biopsies were found to overlap with the final one that was based on an evaluation of all three liver biopsies. Moreover, highly significant correlation was found to exist between the scores of histological parameters of inflammation, fibrosis, necrosis, and steatosis.
Assuntos
Biópsia por Agulha/métodos , Laparoscopia , Hepatopatias/diagnóstico , Fígado/patologia , Adulto , Doença Crônica , Feminino , Humanos , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
"Laparobiopsies" were taken from the right and left liver lobe of 57 patients. Despite some minor discrepancies, the histologic diagnoses "overlapped" in most cases. Moreover, a highly significant correlation was detected between the scores of histologic parameters (inflammation, fibrosis, necrosis and steatosis) evaluated in the two series of biopsies.
Assuntos
Biópsia por Agulha , Laparoscopia , Hepatopatias/diagnóstico , Fígado/patologia , Adulto , Feminino , Humanos , Hepatopatias/patologia , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosAssuntos
Compostos Bicíclicos com Pontes/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Doenças Funcionais do Colo/tratamento farmacológico , Ácidos Cicloexanocarboxílicos , Endoscopia , Parassimpatolíticos/uso terapêutico , Adulto , Idoso , Doenças Funcionais do Colo/diagnóstico , Endoscopia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Vômito/tratamento farmacológicoRESUMO
Five out of seven patients with erosive lichen planus were found to have cirrhotic liver complications. In 2 patients active chronic hepatitis was proven by means of laparoscopy and liver biopsy.