RESUMO
AIM: To validate the utility of hepatic resection combined with complementary radiofrequency ablation (RFA) compared with resection alone for patients with multiple hepatocellular carcinoma (HCC), and to compare these results with those of a previous report. MATERIALS AND METHODS: A total of 78 HCC patients with multiple (≤5) tumours who were initially treated with hepatic resection only (Resection group) or with combined hepatic resection and RFA (Combination group) were included. Overall and disease-free survival were analysed. RESULTS: There were 21 women and 57 men with a median age of 72.5 (64.3-76.8) years. Fifty-three patients were treated with resection alone and 25 received combination therapy. The 3-, 5-, and 7-year cumulative overall survival rates were 81.2%, 68.2%, and 57.1%, respectively, in the Resection group, and 81.3%, 59.6%, and 42.4%%, respectively, in the Combination group (hazard ratio [HR], 1.462; 95% confidence interval [CI], 0.682-3.136; p=0.329). The 1-, 3-, and 5-year cumulative disease-free survival rates were 61.4%, 45.7%, and 39.8%, respectively, in the Resection group, and 53.1%, 18.6%, and 0%, respectively, in the Combination group (HR, 2.080; 95% CI, 1.157-3.737; p=0.014). The overall survival rate was not significantly different between the Resection and Combination groups in patients within the up-to-seven HCC criteria (n=56; HR, 2.101; 95% CI, 0.805-5.486; p=0.130) or those beyond these criteria (n=22; HR, 0.804; 95% CI, 0.197-3.286; p=0.761). CONCLUSIONS: The combination of hepatic resection and RFA therapy may be an effective strategy for HCC patients with multiple tumours.
Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Neoplasias Hepáticas/cirurgia , Idoso , Terapia Combinada , Feminino , Humanos , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
We compared the background characteristics of patients with chronic hepatitis C who achieved eradication of hepatitis C virus (HCV), that is sustained virologic response (SVR), with interferon (IFN)-based versus IFN-free antiviral therapy in Japan. In addition, we used a previously reported risk assessment model to compare the incidence of hepatocellular carcinoma (HCC) after SVR by treatment type. Pretreatment characteristics of 1533 patients who achieved SVR with IFN-based therapy and 1086 patients with IFN-free therapy from five institutions across Japan were compared. The risk of HCC after SVR was assessed based on pretreatment characteristics, and the incidence of HCC after SVR was estimated in both groups. Age and serum alpha-fetoprotein levels were higher, platelet count was lower, and liver fibrosis was more advanced in patients who achieved SVR with IFN-free therapy compared with IFN-based therapy. The incidence of HCC after SVR in the IFN-free group was estimated to be more than twofold higher than in the IFN-based therapy group (7.29% vs. 3.09%, and 6.23% vs. 3.01% when excluding patients who have underwent curative treatment for HCC). There are large differences in pretreatment characteristics between patients who achieved SVR with IFN-based and IFN-free therapies in Japan, which are associated with differential risk of HCC after SVR. These differences can influence the incidence of HCC after SVR and should be taken into consideration when comparing IFN-based and IFN-free therapies in terms of hepatocarcinogenesis suppression with HCV eradication.
Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Neoplasias Hepáticas/epidemiologia , Resposta Viral Sustentada , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hepatite C Crônica/patologia , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Medição de RiscoRESUMO
BACKGROUND: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. MATERIALS AND METHODS: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. RESULTS: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. CONCLUSIONS: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Humanos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. PATIENTS AND METHODS: We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. RESULTS: Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin-bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). CONCLUSION: NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia , Prognóstico , Quinolinas , Estudos RetrospectivosRESUMO
BACKGROUND: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. PATIENTS AND METHODS: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. RESULTS: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group. CONCLUSIONS: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC.
Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia , Prognóstico , QuinolinasRESUMO
We initially conducted a multicenter, randomized trial (n=43), and subsequently a questionnaire study (n=209) of participating hospitals, to evaluate whether infused fresh frozen plasma (FFP) could prevent the occurrence of hepatic veno-occlusive disease (VOD) after stem cell transplantation (SCT). Forty-three patients were divided into two groups: 23 receiving FFP infusions and 20 not receiving it. VOD developed in three patients not receiving FFP. Plasma von Willebrand factor (VWF) antigen levels were lower at days 0, 7 and 28 after SCT in patients receiving FFP than in those not receiving it, whereas plasma ADAMTS13 activity (ADAMTS13:AC) did not differ between them. Plasma VWF multimer (VWFM) was demonstrated to be defective in the high approximately intermediate VWFM during the early post-SCT phase, but there was a significant increase in high VWFM just before VOD onset. This suggests that a relative enzyme-to-substrate (ADAMTS13/high-VWFM) imbalance is involved in the pathogenesis of VOD. To strengthen this hypothesis, the incidence of VOD was apparently lower in patients receiving FFP infusions than in those not receiving it (0/23 vs 3/20) in the randomized trial. Further, the results combined with the subsequent questionnaire study (0/36 vs 11/173) clearly showed the incidence to be statistically significant (0/59 vs 14/193, P=0.033).
Assuntos
Proteínas ADAM/sangue , Hepatopatia Veno-Oclusiva/prevenção & controle , Plasma , Transplante de Células-Tronco , Fator de von Willebrand/análise , Proteína ADAMTS13 , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Hepatopatia Veno-Oclusiva/sangue , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/patologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Plasma/enzimologiaAssuntos
Fístula Brônquica/terapia , Fístula Esofágica/terapia , Neoplasias Esofágicas/complicações , Adesivos Teciduais/uso terapêutico , Idoso , Fístula Brônquica/etiologia , Broncoscopia , Cianoacrilatos/uso terapêutico , Fístula Esofágica/etiologia , Estenose Esofágica/etiologia , Humanos , MasculinoRESUMO
Fifty-five hematopoietic cell lines, including 19 T-, 16 B-, 5 pre-B-, 5 non-T non-B-, 1 erythroid, and 9 myeloid-monocytoid cells, were screened for production of human hematopoietic survival and stem cell growth factor (SCGF) by enzyme immunoassay using anti-SCGF monoclonal antibody. The KPB-M15 myeloid cell line constitutionally secreted a considerable quantity of SCGF, while other T- or myeloid-monocytoid cell lines did not secrete SCGF. Other biomaterials investigated were fetal calf, horse, and human serum; granulocyte-macrophage colony-stimulating factor and erythropoietin preparations; human placental conditioned medium; lectin (phytohemagglutinin, concanavalin A, and pokeweed mitogen); and mixed leukocyte reaction-stimulated leukocyte-conditioned medium. SCGF was detected only in human placental conditioned medium. SCGF produced by the KPB-M15 cells was a protein with a molecular weight of 20,000. The molecule, highly purified by immunoadsorbent affinity chromatography, retained SCGF activity in vitro, e.g., erythroid burst-promoting activity and granulocyte-macrophage-colony potentiation. With the availability of purified SCGF, it is now possible to study in detail the mechanisms regulating hematopoietic stem cells.
Assuntos
Anticorpos Monoclonais/imunologia , Fatores Estimuladores de Colônias/análise , Substâncias de Crescimento/análise , Células-Tronco Hematopoéticas/efeitos dos fármacos , Leucemia Mieloide/metabolismo , Placenta/análise , Linhagem Celular , Cromatografia de Afinidade , Substâncias de Crescimento/isolamento & purificação , Substâncias de Crescimento/farmacologia , Fatores de Crescimento de Células Hematopoéticas , Humanos , Técnicas Imunoenzimáticas , Interleucina-3/análise , Peso MolecularRESUMO
In vivo effect of an immunostimulant, OK-432, on hematopoietic spleen colonies (CFU-S) was investigated in irradiated JCL/ICR mice. Administration of OK-432 i.p. at various times before and/or after irradiation resulted in a significant increase in endogenous CFU-S. This increase was further characterized microscopically by an increase in the number of megakaryocytic colonies. Transplantable exogenous CFU-S also increased when normal bone marrow cells were transplanted into irradiated recipient mice previously given OK-432 i.p. Treatment with OK-432 gave rise to an earlier recovery of granulocyte and, particularly, platelet counts in the peripheral blood after irradiation. All these findings indicate that an increase in CFU-S is associated with activated hematopoietic microenvironment by OK-432.
Assuntos
Vacinas Bacterianas/administração & dosagem , Produtos Biológicos/administração & dosagem , Células-Tronco Hematopoéticas , Picibanil/administração & dosagem , Baço/citologia , Animais , Transplante de Medula Óssea , Ensaio de Unidades Formadoras de Colônias , Feminino , Granulócitos , Injeções Intraperitoneais , Contagem de Leucócitos , Camundongos , Contagem de PlaquetasRESUMO
PURPOSE: We conducted a multicenter study of differentiation therapy with all-trans retinoic acid (ATRA) followed by intensive chemotherapy in patients with newly diagnosed acute promyelocytic leukemia (APL) and analyzed the prognostic factors for predicting complete remission (CR), event-free survival (EFS), and disease-free survival (DFS). PATIENTS AND METHODS: All patients received ATRA until CR. If patients had an initial leukocyte count greater than 3.0 x 10(9)/L, they received daunorubicin (DNR) and behenoyl cytarabine (BHAC). During therapy, if patients showed blast and promyelocyte counts greater than 1.0 x 10(9)/L, they received additional DNR and BHAC. After achieving CR, patients received three courses of consolidation and six courses of maintenance/intensification chemotherapy. RESULTS: Of 198 registered, 196 were assessable (age range, 15 to 86 years; median, 46) and 173 (88%) achieved CR. Multivariate analysis showed that no or minor purpura at diagnosis (P = .0046) and age less than 30 years (P = .0076) were favorable factors for achievement of CR. Predicted 4-year overall survival and EFS rates were 74% and 54%, respectively, and the 4-year predicted DFS rate for 173 CR patients was 62%. Multivariate analysis showed that age less than 30 years (P = .0003) and initial leukocyte count less than 10 x 10(9)/L (P = .0296) were prognostic factors for longer EFS, and initial leukocyte count less than 10.0 x 10(9)/L was a sole significant prognostic factor for longer DFS (P = .0001). CONCLUSION: Our results show that age, hemorrhagic diathesis, and initial leukocyte count are prognostic factors for APL treated with ATRA followed by intensive chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Transplante de Medula Óssea , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Leucemia Promielocítica Aguda/mortalidade , Leucemia Promielocítica Aguda/patologia , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Resultado do TratamentoRESUMO
PURPOSE: We analyzed complete remission (CR), disease-free survival (DFS), and event-free survival (EFS) rates in two groups of patients treated with either N4-behenoyl-1-beta-D-arabinosylcytosine (BHAC) or cytarabine, and analyzed DFS with or without ubenimex, a biologic response modifier. PATIENTS AND METHODS: Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either BHAC or cytarabine as remission-induction combination chemotherapy and two courses of consolidation therapy. After maintenance/intensification therapy, patients in CR were randomized to receive either ubenimex and no drug. RESULTS: Of 341 patients registered, 326 were assessable. The age of assessable patients ranged from 15 to 82 years (median, 48). The overall CR rate was 77%: 72% in the BHAC group and 81% in the cytarabine group, and there was a significant difference between the two groups (P = .035, chi 2 test). The predicted 55-month EFS rate of all patients was 30%: 23% in the BHAC group and 35% in the cytarabine group, with a significant difference between groups (P = .0253). The predicted 55-month DFS rate of all CR patients was 38% and that of CR patients less than 50 years of age was 47%. There was no significant difference in DFS between the ubenimex group and the group that did not receive ubenimex. CONCLUSION: Analyses of our clinical trial showed that the use of BHAC in remission-induction therapy and in consolidation therapy resulted in poorer CR and EFS rates in adult AML patients compared with the use of cytarabine at the doses and schedules tested. Immunotherapy with ubenimex after the end of all chemotherapy did not improve DFS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Distribuição de Qui-Quadrado , Citarabina/administração & dosagem , Citarabina/análogos & derivados , Daunorrubicina/administração & dosagem , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucina/administração & dosagem , Leucina/análogos & derivados , Leucemia Mieloide/mortalidade , Modelos Logísticos , Masculino , Mercaptopurina/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Prednisolona/administração & dosagem , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Resultado do TratamentoRESUMO
The purging efficacy of positive selection of autologous CD34+ PBSC with a clinical scale method of magnetic-activated cell sorting system (CliniMACS) was investigated in 48 patients with non-Hodgkin's lymphoma (NHL). The median purity and recovery rate of the CD34+ cells post-selection were 93.3% (range 32.6-99.3) and 72.2% (range 20.5-309.8), respectively. The real-time PCR method to detect the patient-specific monoclonal immunoglobulin heavy chain gene rearrangement (minimal residual tumor; MRT) and CD19 and CD20 positivities were used for the detection of contaminating NHL cells before and after CD34+ selection. After selection, the median (range) depletion rate of MRT was 2.53 (1.52-4.78) log, and that of CD19+ cell and CD20+ cell was 2.46 (0.74-3.64) log and 2.32 (0.40-4.01) log, respectively. In 41 patients, high-dose chemotherapy was performed, followed by the transplantation of the isolated CD34+ cells. Rapid neutrophil recovery as well as platelet recovery was seen with a median time to reach 0.5 x 10(9)/l neutrophils of 10 days (range 8-13) and 20 x 10(9)/l platelets of 14 days (range 10-34), respectively. The present study demonstrated that CliniMACS is a highly effective positive selection method and a high purging efficacy could be obtained without compromising the hematopoietic reconstitution capacity of the graft in NHL patients undergoing high-dose chemotherapy.
Assuntos
Antígenos CD34 , Sobrevivência de Enxerto , Separação Imunomagnética , Linfoma não Hodgkin/terapia , Células Neoplásicas Circulantes/patologia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adulto , Antineoplásicos/uso terapêutico , Células Clonais , Feminino , Rearranjo Gênico , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Transplante AutólogoRESUMO
We treated 70 acute promyelocytic leukemia (APL) patients with daily oral 45 mg/m2 all-trans-retinoic acid (ATRA) in two multi-institutional prospective studies. Of 64 evaluable patients, 21 were refractory to initial induction chemotherapy; 10 were refractory to salvage chemotherapy; 17, five, and four were in the first, second and, third relapse, respectively; and seven were previously untreated due to old age. In the first study with ATRA from China, 18 out of 22 (82%) evaluable patients achieved complete remission (CR). Initial peripheral leukemia cell counts were significantly less in the CR cases (p < 0.01); < 100/microliters in 17 out of 18 CR cases, and > or = 200/microliters in all failure cases. In the second study with ATRA from Hoffmann-La Roche, if initial leukemia cell counts were more than 200/microliters, chemotherapy was first given and then ATRA was started. Of 42 evaluable patients, 36 (86%) achieved CR. Morphological evidence of differentiation was noted in all CR cases. Patients achieving CR received standard consolidation and maintenance chemotherapies, and the 20-month predicted disease-free survival rate is 76% for cases achieving their first CR with ATRA. Toxicities attributable to ATRA were minimal and included cheilitis, xerosis, dermatitis, gastrointestinal disorders, bone pain, liver damage, and high serum triglyceridemia.
Assuntos
Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Criança , Feminino , Humanos , Japão , Leucemia Promielocítica Aguda/mortalidade , Leucemia Promielocítica Aguda/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Taxa de Sobrevida , Tretinoína/efeitos adversosRESUMO
We asked 2 questions in this study. First was the additional effect of VCR in induction therapy, and the second was the duration of maintenance therapy. Adult AML were treated by an individualized response-oriented induction therapy with behenoyl Ara-C 200 mg/m2 daily + 6MP 70 mg/m2 daily + prednisolone 40 mg/m2 on days 1-4 + DNA 40 mg/m2 on days 1-3 and additionally on days 7, 8, 11, 12 (for M3, DNR 50 mg/m2 daily) (BHAC-DMP) until bone marrow became severely hypoplastic with less than 5% of blasts. Patients were randomized to BHAC-DMP or BHAC-DMP + VCR 0.35 mg/m2 on days 1-4. After obtaining CR, 3 courses of intensive consolidation therapy were given together with I.T. MTX+Ara-C+PSL. Maintenance intensification therapy was randomized to either 4 or 12 courses given every 2 months. Patients of age greater than or equal to 60 received about 2/3 reduced doses. From June 1987 to Sept. 1989, 265 consecutive adult AML were registered from 19 institutions and 258 were evaluable. Age ranged from 15 to 79 (med., 48). Out of 258, 200 (77.5%) achieved CR (80% in 209 of age less than 60 and 65% in 49 of age greater than or equal to 60). Unexpectedly, addition of VCR reduced the high CR rate of BHAC-DMP significantly (84% to 70%, p = 0.007). At the median follow-up of 37 mo., overall survival is 37%, and event-free survival (EVS) 27%. Survival, continuing CR and disease-free survival (DFS) rates of 200 CR cases are 45%, 40% and 35%, respectively. Patients received 12 courses of maintenance therapy showed better DFS (P = 0.0555). The VCR group had significantly worse EFS. By multivariate analysis, significant prognostic factors for the achievement of CR were age less than 60, PS 0-2 and no addition of VCR. Significant factors for longer DFS were induction of CR by one course, FAB M3 or M5 and age less than 50. The present multi-institutional study confirmed the high CR rates of the response-oriented individualized therapy reported from several centers in Japan, but failed to support an additional effect of VCR reported from one center.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Citarabina/administração & dosagem , Citarabina/análogos & derivados , Daunorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Japão , Leucemia Mieloide/mortalidade , Masculino , Mercaptopurina/administração & dosagem , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Indução de Remissão , Vincristina/administração & dosagemRESUMO
The effect of graft-versus-host disease (GVHD) on relapse incidence and survival has been analyzed in several studies, but previous studies included heterogeneous patients. Therefore, we analyzed the data of 2114 patients who received unmanipulated bone marrow graft from an HLA-identical sibling donor with a GVHD prophylaxis using cyclosporin A and methotrexate. Among the 1843 patients who survived without relapse at 60 days after transplantation, 435 (24%) developed grade II-IV acute GVHD. Among the 1566 patients who survived without relapse at 150 days after transplantation, 705 (47%) developed chronic GVHD. The incidence of relapse was significantly lower in patients who developed acute or chronic GVHD, but disease-free survival (DFS) was significantly inferior in patients who developed acute GVHD. A benefit of 'mild' GVHD was only seen in high-risk patients who developed grade I acute GVHD. The strongest association between GVHD and a decreased incidence of relapse was observed in patients with standard-risk acute myelogenous leukemia/myelodysplastic syndrome. In conclusion, the therapeutic window between decreased relapse and increased transplant-related mortality due to the development of GVHD appeared to be very narrow.
Assuntos
Transplante de Medula Óssea , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/complicações , Metotrexato/uso terapêutico , Adulto , Idoso , Transplante de Medula Óssea/mortalidade , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Efeito Enxerto vs Leucemia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
Granulocyte-macrophage progenitor cells (CFUc) in the bone marrow cells from mice before, and 12 hours to 7 days after intraperitoneal administration of vinblastine (VLB; 4 mg/kg) were serially investigated until day 14 of culture. The number of CFUc rose to peak levels on days 7 and 4 of culture in the whole bone marrow cells obtained before and two to four days after VLB treatment, respectively. A small peak found on day 11 of culture was marked up to 2 days after VLB treatment when fresh medium containing colony-stimulating factor was added on day 7. Each CFUc in the bone marrow cells fractionated by velocity sedimentation, counted on days 4, 7 and 11 of culture, showed distinct subpopulations of varying cell size. There was a correlation between the amount of each CFUc with cellularity and cytodifferential before and after the VLB treatment. Recruitment of stem cells through three CFUc subpopulations in the CFUc compartment is accentuated during convalescence following VLB-induced myelosuppression.
Assuntos
Células-Tronco Hematopoéticas/efeitos dos fármacos , Vimblastina/farmacologia , Animais , Células da Medula Óssea , Separação Celular , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Meios de Cultura , Feminino , Técnicas In Vitro , Camundongos , Fatores de TempoRESUMO
A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.
Assuntos
Fatores Estimuladores de Colônias/uso terapêutico , Leucemia/tratamento farmacológico , Doença Aguda , Adulto , Antineoplásicos/uso terapêutico , Transplante de Medula Óssea , Fatores Estimuladores de Colônias/efeitos adversos , Avaliação de Medicamentos , Feminino , Fator Estimulador de Colônias de Granulócitos , Humanos , Infecções/tratamento farmacológico , Leucemia/patologia , Leucemia/terapia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Contagem de Leucócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Proteínas RecombinantesRESUMO
In the cytoplasm of peripheral blood lymphocytes in 3 of 13 patients with myotonic dystrophy, myelin-like structures were observed electronmicroscopically. Some were connected to the cytoplasmic membranes, and some were surrounded by a limiting membrane possessing acid phosphatase activity. These findings suggest an aberration of cytoplasmic membranes in lymphocytes. Similar structures had appeared in lymphocytes of normal rats that became myotonic with 20, 25-diazacholesterol. These findings suggest that a primary genetic defect in human myotonic dystrophy, which participates in the formation of myelin-like structures in lymphocytes, might be also responsible for the occurrence of a myotonic phenomenon.
Assuntos
Linfócitos/patologia , Distrofias Musculares/patologia , Distrofia Muscular Animal/patologia , Adolescente , Adulto , Animais , Azacosterol/farmacologia , Feminino , Humanos , Corpos de Inclusão/ultraestrutura , Linfócitos/efeitos dos fármacos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Distrofia Muscular Animal/induzido quimicamente , Proteínas da Mielina/metabolismo , Ratos , Ratos EndogâmicosRESUMO
A novel Philadelphia (Ph1) chromosome positive cell line, designated KYO-1, was established from the peripheral blood of a patient with chronic myelogenous leukemia (CML) in blastic crisis. Although this line had a unique capacity to differentiate spontaneously along the erythroid and monocytoid lineages as evidenced by cytochemical analysis for the first several months, the capacity was gradually lost after repeated passages. The results suggest that KYO-1 is an undifferentiated myeloid cell line. This cell line provides a useful source for studying differentiation and proliferation of pluripotent stem cells from CML in blastic crisis.
Assuntos
Cromossomos Humanos 21-22 e Y , Leucemia Mieloide/genética , Adulto , Diferenciação Celular , Linhagem Celular , Histocitoquímica , Humanos , Leucemia Mieloide/imunologia , Leucemia Mieloide/patologia , MasculinoRESUMO
A new water-soluble nitrosourea derivative, methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), was found to be useful for the treatment of chronic myelogenous leukemia (CML) in the chronic phase. To compare the efficacy of MCNU with that of busulfan, patients were randomized. In the 40 patients administered MCNU, the median time to the achievement of a complete remission (CR) was 50 days. This value was shorter than that observed in 37 patients administered busulfan (126 days, p less than 0.05). There were no differences in the rate of CR achieved, mortality, median time to the onset of blast crisis (BC), BC rate, or survival rate during the observation period. The overall incidence of side effects was higher for MCNU (31%) than for busulfan (15%), but the symptoms were mild, transient and tolerable for most patients. These results suggest that MCNU is a safe and valuable addition to the therapeutic repertoire for the control of CML.