RESUMO
This study evaluated the efficacy and safety of salvage chemotherapy with gemcitabine, carboplatin, dexamethasone, and rituximab (GCD ± R) for Japanese patients with relapsed or refractory non-Hodgkin lymphoma (NHL). A multicenter, phase II trial of GCD ± R administered every 3 weeks for up to 6 cycles was conducted. Rituximab was administered as a therapeutic strategy for CD20-positive lymphoma. The primary endpoint was the complete response (CR) rate. Secondary endpoints included the overall response (OR) rate, overall survival (OS), progression-free survival (PFS), toxicity, and success rate of peripheral blood stem cell collection for eligible transplant patients. A total of 25 patients (median age 66 years) were evaluated, with a median follow-up period of 66.7 months. CR and OR rates were 28% and 52%, respectively. Median PFS and OS were 8.7 and 32.2 months, respectively. The major toxicity was myelosuppression, but the regimen was generally well-tolerated, with a low incidence of febrile neutropenia (20%) and no treatment-related deaths. Of the 6 patients who were eligible for autologous stem cell transplantation and underwent peripheral blood stem cell mobilization, the required number of CD34-positive cells was collected in 5 (83%). All 6 proceeded to transplantation and achieved successful engraftment without recurrence. The present results suggest that GCD ± R may be effective and well-tolerated in Japanese patients with relapsed or refractory NHL. However, further investigation is needed to confirm these results.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin , Humanos , Idoso , Rituximab/efeitos adversos , Gencitabina , Carboplatina/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/patologia , Transplante Autólogo , Linfoma não Hodgkin/tratamento farmacológico , Dexametasona/efeitos adversos , Terapia de Salvação/métodosRESUMO
Oral mucositis is a common and distressing complication in patients receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). We reported previously in a single-center retrospective analysis that zinc-L-carnosine (polaprezinc [PZ]) reduced the incidence of oral mucositis associated with HSCT. To verify the accuracy of the prophylactic effect of PZ against oral mucositis, we carried out a multi-institutional prospective randomized controlled study. Patients were randomly allocated to either the prevention group, in which PZ lozenge treatment was started before chemotherapy, or the control group, in which administration of PZ lozenges was initiated immediately after the onset of Grade 2 oral mucositis. Oral mucositis was evaluated daily from the start of chemotherapy to 35 days after transplantation. A total of 91 patients were enrolled, and 88 patients (47 in the control group and 41 in the prevention group) were eligible for data analysis. The incidence of Grade ≥2 but not Grade ≥3 oral mucositis was significantly reduced in the prevention group compared to the control group (44.7% in control group vs 22.0% in the prevention group, P = .025). There were no significant differences in the incidence rates of other adverse events or the rate of engraftment (95.6% vs 97.2%, P = .693) between the two groups. These findings suggest that PZ lozenge is effective for prophylaxis against Grade ≥2 oral mucositis associated with chemotherapy in patients undergoing HSCT without any influence on the HSCT outcome.
Assuntos
Antiulcerosos/administração & dosagem , Antineoplásicos/efeitos adversos , Carnosina/análogos & derivados , Compostos Organometálicos/administração & dosagem , Estomatite/induzido quimicamente , Estomatite/tratamento farmacológico , Adolescente , Adulto , Idoso , Carnosina/administração & dosagem , Feminino , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Adulto Jovem , Compostos de Zinco/administração & dosagemRESUMO
Pirarubicin (tetrahydropyranyl adriamycin [THP]) is an anthracyclin with less cardiotoxicity than doxorubicin (DOX). We previously reported the efficacy and safety of R-THP-COP consisting of rituximab (R), THP, cyclophosphamide (CPA), vincristine (VCR), and prednisolone (PSL) for diffuse large B cell lymphoma (DLBCL) in phase 2 studies. Here, we prospectively compared the efficacy and safety of the R-THP-COP and standard R-CHOP regimen (consisting of R, CPA, DOX, VCR, and PSL) in a noninferiority phase 3 trial. This prospective, randomized phase 3 study included patients younger than 70 years of age with previously untreated DLBCL. The regimen consisted of R (day 1), DOX, or THP (day 3), CPA (day 3), VCR (day 3), and PSL for 5 days every 3 weeks for 6 to 8 cycles. Between July 5, 2006 and June 11, 2013, 81 patients were randomly assigned to the treatment groups (R-CHOP group, 40 patients; R-THP-COP group, 41 patients). R-THP-COP was noninferior to R-CHOP, as assessed by the primary endpoint of complete response rate (85% vs 85% respectively). With a median follow-up of 75.2 months, the 5-year overall survival was 87% in the R-CHOP group and 82% in the R-THP-COP group (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.31-2.49; P = .82). The 5-year progression-free survival was 74% in the R-CHOP group and 79% in the R-THP-COP group (HR: 1.37, 95% CI: 0.56-3.55; P = .49). No grade 3 cardiac side effects were observed in either group. No serious late adverse reactions were observed in either group, with the exception of therapy-related acute myeloid leukemia in the R-THP-COP group. These data indicate that R-THP-COP is noninferior to R-CHOP with regard to clinical response, and has an acceptable safety profile. Thus, this regimen may be an alternative therapy to R-CHOP.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Rituximab , Taxa de Sobrevida , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
We have reported the efficacy of the salvage chemotherapy P-IMVP16/CBDCA for patients with diffuse large B cell lymphoma (DLBCL) who had previously received CHOP before the availability of rituximab (R). Here, we confirmed the efficacy of R combined with P-IMVP16/CBDCA as a salvage chemotherapy for patients with DLBCL, who had previously received R-CHOP. We retrospectively analysed 59 patients with relapse or refractory DLBCL (38 male patients and 21 female patients) presenting between June 2004 and June 2013. The patients received R 375 mg/m2 on day 1, methylprednisolone 1000 mg/body for 3 days (from day 3 to day 5), ifosfamide 1000 mg/m2 for 5 days (from day 3 to day 7), methotrexate 30 mg/m2 on day 5 and day 12, etoposide 80 mg/m2 for 3 days (from day 3 to day 5), and carboplatin 300 mg/m2 on day 3 every 21 days. Patients aged 70 years or older were given 75% of the standard dose. The overall response rate (complete response + partial response) was 64.4%. The 2-year overall survival rate was 55.3%. The 2-year progression free survival rate was 34.7%. The 2-year overall survival rate was 61.5% for the relapse patients, and 15.6% for the refractory patients (p < 0.0001). One patient died because of sepsis related to the treatment regimen. Non-hematological adverse effects were mild and tolerable. The R-P-IMVP-16/CBDCA regimen displayed a significant activity in relapsed DLBCL, with acceptable toxicity, and should be considered a candidate for salvage chemotherapy. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Ciclofosfamida , Doxorrubicina , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Ifosfamida/efeitos adversos , Ifosfamida/uso terapêutico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona , Prognóstico , Recidiva , Retratamento , Estudos Retrospectivos , Rituximab , Terapia de Salvação , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , VincristinaRESUMO
The CHOP regimen consisting of cyclophosphamide, doxorubicin (DOX), vincristine and prednisolone has been the most used regimen for peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Pirarubicin [tetrahydropyranyladriamycin (THP)], a derivative of DOX, is an anthracycline with reportedly less cardiotoxicity than DOX. Here, we confirmed the efficacy of THP-COP using THP instead of DOX in the treatment of PTCL-NOS. The study protocol employed a retrospective, consecutive entry design. We retrospectively analysed 56 patients with PTCL-NOS who had received THP-COP or CHOP. These regimens were performed every 21 days. Twenty-nine patients received THP-COP, and 27 received CHOP. There were no significant differences in known prognostic factors, including in the International Prognostic Index (IPI) and the prognostic index for T-cell lymphoma (PIT), between the two groups. Complete remission rates in patients with THP-COP and CHOP were 52% in both groups; the 3-year overall survival (OS) rates were 67% and 52% (p = 0.074), and the 3-year progression-free survival (PFS) rates were 51% and 29% (p = 0.070), respectively. In patients with low IPI (low or low-intermediate), THP-COP had significantly better 3-year OS (100% vs. 64%; p < 0.001) and 3-year PFS (75% vs. 33%; p < 0.05) than CHOP. Similar differences between THP-COP and CHOP were observed in patients with a low PIT (groups 1 or 2). Our study showed that THP-COP produced results equivalent to CHOP regarding efficacy and safety in patients with PTCL-NOS. In patients with low IPI or PIT, THP-COP resulted in significantly better prognosis. Copyright © 2015 John Wiley & Sons, Ltd.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células T Periférico/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Humanos , Linfoma de Células T Periférico/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Vincristina/administração & dosagemRESUMO
BACKGROUND: Serum soluble tumor necrosis factor receptor 2 (sTNFR2) concentration predicted the clinical outcome of patients with aggressive non-Hodgkin's lymphoma including diffuse large B-cell lymphoma (DLBCL) treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) in our previous study. However, after rituximab (R) was introduced in clinical practice, R-CHOP replaced CHOP as the standard therapy for DLBCL. PATIENTS AND METHODS: In this study, we re-evaluated the prognostic significance of serum sTNFR2 in 154 patients with DLBCL treated with R-CHOP. RESULTS: Five-yr overall survival (5-yr OS) rates with sTNFR2 ≥20 ng/mL and <20 ng/mL were 29.2% and 83.3% (P < 0.0001), respectively, and the corresponding 5-yr progression-free survival (5-yr PFS) rates were 26.9% and 76.4% (P < 0.0001), respectively. A multivariate analysis revealed that serum sTNFR2 and complete remission (CR) were independent prognostic factors for both OS (CR: P < 0.0001, sTNFR2: P = 0.0001) and PFS (CR: P < 0.0001, sTNFR2: P = 0.0001). The prognosis of patients with poor risk groups according to the revised International Prognostic Index who also had high serum sTNFR2 was especially poor. CONCLUSION: Serum sTNFR2 might be a powerful prognostic factor for patients with DLBCL in the rituximab era.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Idoso , Anticorpos Monoclonais Murinos/uso terapêutico , Biomarcadores Tumorais/genética , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Esquema de Medicação , Feminino , Expressão Gênica , Humanos , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prednisona/uso terapêutico , Prognóstico , Estudos Prospectivos , Receptores Tipo II do Fator de Necrose Tumoral/genética , Rituximab , Análise de Sobrevida , Vincristina/uso terapêuticoRESUMO
We compared the predictive ability of the International Prognostic Index (IPI), a frequently used prognostic model for peripheral T-cell lymphoma (PTCL), with that of a type-specific prognostic model, the Prognostic Index for PTCL-U (PIT). We retrospectively analyzed 113 patients diagnosed with PTCL. The median age was 67 years (range, 16-88 years), 75 patients (66%) were male, and the most common disease type was PTCL, not otherwise specified (69%). With a median follow-up of 6.8 years (interquartile range, 2.7-9.9 years), 5-year survival rates for the four groups in IPI were 85%, 62%, 49%, and 13%, respectively. Similarly, 5-year survival rates for the four groups in PIT were 83%, 64%, 49%, and 19%, respectively. The area under the receiving operating characteristic curve for predicting mortality from PIT (0.725) was not significantly different from that from the IPI (0.685, P = 0.134). Multivariable analysis showed that performance status ≥ 2 (P < 0.0001) and extranodal lesions ≥ 2 (P = 0.029) were significantly associated with lower overall survival. The present study found no significant difference in prognostic ability between the IPI and PIT for PTCL, and both models appear useful as predictive models.
Assuntos
Linfoma de Células T Periférico , Humanos , Masculino , Idoso , Feminino , Prognóstico , Linfoma de Células T Periférico/patologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The controlling nutritional status (CONUT) score is a simplified nutritional index calculated from serum albumin, total cholesterol, and total lymphocyte count. This study evaluated the prognostic impact of the CONUT score on overall survival (OS) in patients with peripheral T-cell lymphoma (PTCL). A multicenter, retrospective cohort study including 99 patients with PTCL was conducted. The CONUT score was significantly higher in the non-survivor group (median 5, range 0-12) than in the survivor group (median 3, range 0-11; p = 0.026). The CONUT score was an independent prognostic factor in a multivariable Cox proportional hazards model (hazard ratio 1.119, 95% confidence interval 1.021-1.227, p = 0.017). No significant effect-modification by the International Prognostic Index (IPI) was observed, and the CONUT score affected the prognosis of PTCL regardless of the IPI (P for interaction = 0.208). In conclusion, the CONUT score is an independent prognostic factor for PTCL irrespective of IPI category.
Assuntos
Linfoma de Células T Periférico , Estado Nutricional , Humanos , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/terapia , Avaliação Nutricional , Prognóstico , Estudos RetrospectivosRESUMO
This phase II clinical trial aimed to evaluate the efficacy and safety of the combination therapy of bendamustine, cytarabine, and rituximab (BRAC) in patients with relapsed or refractory follicular lymphoma (FL) or mantle cell lymphoma (MCL). Thirteen patients were enrolled and received a median of 4 cycles (range 2-6) of BRAC. The complete response rate was 61.5%, and the overall response rate was 84.6%; the 2-year overall survival was 76.9%, and the 2-year progression-free survival was 69.2%. Although all patients received G-CSF prophylaxis, grade 3 or higher neutropenia was observed in all cycles, and the incidence of febrile neutropenia was 20%. Grade 4 thrombocytopenia was observed in 92.5% of all cycles, and platelet transfusion was performed in 94%. Although hematological toxicity was relatively high, BRAC therapy was effective for relapsed and refractory FL or MCL. Further studies are needed to determine the optimal dose of BRAC therapy.Trial registration The UMIN Clinical Trials Registry, UMIN000009797. Registered 17 January 2013, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000011103.
RESUMO
BACKGROUND: We have previously reported that serum interleukin-18 (IL-18) concentration predicted the clinical outcome of patients with aggressive non-Hodgkin's lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). When rituximab (R) was added to this regimen, the prognosis of diffuse large B-cell lymphoma (DLBCL) was markedly improved. PATIENTS AND METHODS: In this study, we re-evaluated the prognostic significance of serum IL-18 in 227 DLBCL patients. Seventy-three patients received CHOP before R-era, and 154 patients received rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) recently. RESULT: Four-year overall survival (4-yr OS) rates for patients in CHOP group with IL-18 ≥720 pg/mL and <720 pg/mL were 8.2% and 67.3% (P<0.0001), respectively, and 4-yr OS rates with IL-18 ≥590 and <590 pg/mL in R-CHOP group were 53.4% and 77.8% (P=0.0008), respectively. Multivariate analysis revealed that serum IL-18 correlated most significantly with OS and progression-free survival (PFS) in both groups (OS: P<0.0001, PFS: P<0.0001, in CHOP group; OS: P=0.0147, PFS: P=0.0084 in R-CHOP group). The high serum IL-18 patients with poor prognostic group in revised IPI or with non-germinal center B-cell phenotype had a very poor prognosis. CONCLUSION: Serum IL-18 might be a powerful prognostic factor for DLBCL in R-era.
Assuntos
Interleucina-18/sangue , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Prognóstico , Rituximab , Análise de Sobrevida , Vincristina/uso terapêutico , Adulto JovemRESUMO
Peripheral T-cell lymphoma (PTCL) with a follicular growth pattern is very rare. Herein, a case of follicular variant of PTCL in a 50-year-old man who complained of tonsillar and generalized lymph node swelling is reported. The resected tonsil revealed a vague nodular growth pattern of atypical cells, medium to large in size, with abundant pale cytoplasm. The lymphoma cells were CD3(+) CD4(+) CD5(+) CD8(-) CD10(+) CD56(-) CD57(-) BCL6(+) PD-1(+) CXCL13(+) and were associated with a meshwork of CD21(+) follicular dendritic cells. Molecular studies revealed clonal rearrangement of the T-cell receptor gamma chain gene but not of the immunoglobulin gene. Cytogenetic analysis disclosed a complex abnormality in 18 of 20 cells with the exclusion of t(5; 9). These findings suggest that the present case is a follicular variant of PTCL derived from follicular T-helper cells.
Assuntos
Linfoma Folicular/genética , Linfoma Folicular/patologia , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patologia , Antígenos CD/metabolismo , Células Dendríticas Foliculares/imunologia , Diagnóstico Diferencial , Rearranjo Gênico da Cadeia gama dos Receptores de Antígenos dos Linfócitos T/genética , Humanos , Imuno-Histoquímica , Linfonodos/patologia , Linfoma Folicular/imunologia , Linfoma Folicular/metabolismo , Linfoma de Células T Periférico/metabolismo , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons/métodos , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: The aim of this study was to assess the prognostic factors of peripheral T-cell lymphoma, unspecified (PTCL-U). PATIENTS AND METHODS: We retrospectively analyzed 30 cases fulfilling the criteria of PTCL-U defined by the World Health Organization classification. The patients were treated with 6-8 cycles of a CHOP or THP (pirarubicin)-COP regimen. RESULTS: A high serum sIL-2R level (> or =2,000 U/ml) at onset was associated with a low complete remission rate. Patients with high sIL-2R had significantly lower survival rates (5 year, 15.1%) than those with low sIL-2R (<2,000 U/ml) (100%) (P < 0.005). Factors associated with worse overall survival in a univariate analysis were high sIL-2R (P < 0.005), high age (>60 years) (P < 0.05), poor performance status (P < 0.01) and poor international prognostic index (P < 0.05). No correlation was observed between sIL-2R and other markers. Multivariate analysis showed that only sIL-2R was a prognostic factor for overall survival (P < 0.01). CONCLUSION: The results suggest that a high serum sIL-2R level predicts a poor prognosis in PTCL-U.
Assuntos
Linfoma de Células T Periférico/sangue , Receptores de Interleucina-2/sangue , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Feminino , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Recent advances in the treatment of hematological malignancies often induce febrile neutropenia (FN) due to severe myelosuppression. The aim of this study was to evaluate the safety and efficacy of biapenem in such FN. METHODS: Candidate patients were admitted to our hospital and were treat of their hematological malignancy from February 2005 to March 2006. They gave written informed consent to enter this study in advance. When the diagnosis of FN was established among them, those patients received intravenous biapenem 0.6 g every 12 hours. This trail was approved by our institutional review board. RESULTS: A total of 54 consecutive patients were registered and 49 patients were evaluable for response. The median age was 61. The underlying diseases were acute lymphocytic leukemia in 6 cases, acute myelocytic leukemia in 21, multiple myeloma in 3, and non-Hodgkin's lymphoma in 19. The response rate was 78% (excellent response: 51%, good response: 27%, minor response: 6%, no response: 16%). In patients with neutrophil counts under 500/microl, the response rate was 73%. Infectious death or other serious adverse events were not observed. CONCLUSION: Biapenem is effective and safe for treating FN.
Assuntos
Anti-Infecciosos/uso terapêutico , Leucemia Mieloide Aguda/complicações , Linfoma não Hodgkin/complicações , Mieloma Múltiplo/complicações , Neutropenia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Tienamicinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/administração & dosagem , Feminino , Febre/tratamento farmacológico , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Tienamicinas/administração & dosagemRESUMO
PURPOSE: To evaluate the efficacy and safety of a novel low dose chemotherapy as a remission induction regimen for elderly de novo AML patients ineligible for intensive chemotherapy. METHOD: Fifty consecutive patients, aged 60 to 85, with untreated de novo AML were enrolled. Patients with poor PS or defined non-hematological complications were given continuous drip infusion of low dose cytarabine (Ara-C), 20 mg/body and etoposide (VP-16), 50 mg/body for 10 days (AV group). Patients without those comorbidities were given intensive induction therapy (S group). After achieving complete remission (CR), S group patients and those with improved PS in AV group received consolidation chemotherapy with intensive regimen (S-S or AV-S group), and other patients received AV regimen repeatedly (AV-AV group). RESULTS: Eighteen (64%; 95% confidence interval (CI), 0.47-0.82) of 28 patients in AV group and 16 (73%; 95% CI, 0.54-0.91) of 22 patients in S group achieved CR, respectively. The 1-year OS rates of the patients in the AV-AV group (n = 9), AV-S group (n = 9), and S-S group (n = 16) were 22, 81, and 78%, respectively. Although the sample size was small, no significant difference was observed for the 1-year OS rate between the AV-S and S-S groups. Regimen related death were 4 patients in S group, while no patient in AV group. CONCLUSION: Therapeutic strategy consisting of remission induction using AV regimen and consolidation using intensive regimen after improving PS is beneficial in the management of elderly AML patients who have difficulty in tolerating for intensive induction chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Resultado do TratamentoRESUMO
PURPOSE: The aim of the present study was to assess the prognostic significance of serum soluble interleukin-2 receptor (sIL-2R) in aggressive non-Hodgkin's lymphoma (NHL). METHODS: One hundred and thirteen consecutive patients with previously untreated aggressive NHL (diffuse large B-cell lymphoma, 96; peripheral T-cell lymphoma, 17) prospectively participated in this study between 1995 and 2001. The patients were treated with 6-8 cycles of a CHOP or THP (pirarubicin)-COP regimen. RESULTS: A high serum sIL-2R level (2,000 U/ml and over) at onset was associated with a low complete remission rate. Patients with high sIL-2R had significantly lower survival rates (5-year, 24%) than those with low sIL-2R (under 2,000 U/ml) (74%) (P<0.01). Multivariate analysis employing sIL-2R levels and conventional prognostic factors demonstrated that high sIL-2R, presence of B-symptoms, and advanced age (60 years and older) were significantly unfavorable variables for overall survival. In addition, we attempted to use sIL-2R in combination with the International Prognostic Index (IPI). The patients in the high (H) risk group and those with high sIL-2R in the low-intermediate (LI)/high-intermediate (HI) risk group had significantly lower survival rates than the patients in the low (L) risk group and those with low sIL-2R in the LI/HI risk group (P<0.001). CONCLUSION: The results suggest that a high serum sIL-2R level predicts a poor prognosis in aggressive NHL and may be a useful biomarker for selecting appropriate treatment when used in combination with the IPI.
Assuntos
Biomarcadores Tumorais/análise , Linfoma Difuso de Grandes Células B/patologia , Linfoma de Células T Periférico/patologia , Receptores de Interleucina-2/sangue , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Receptores de Interleucina-2/química , Fatores de Risco , Solubilidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
To facilitate more economical medical care, we carried out a prospective study of whether a THP-COP regimen (cyclophosphamide, pirarubicin, vincristine, and prednisolone) with low-dose granulocyte colony-stimulating factor (G-CSF) would effectively treat non-Hodgkin's lymphoma (NHL). From April 2003 through March 2004, we enrolled 19 consecutive patients with newly diagnosed NHL treated at our hospital. The patients were divided into young and elderly groups. Each patient underwent chemotherapy with 8 courses of a THP-COP regimen with a 50-microg dose of lenograstim. Age- and sex-matched historical control patients (n = 141) received NHL diagnoses between 1998 and 2003. Each patient in the control group underwent the same chemotherapy and received a 100-microg dose of lenograstim. The mean (+/-SD) total amounts of G-CSF per cycle of chemotherapy were 332 +/- 103 microg (young patients) and 345 +/- 128 microg (elderly patients) in the low-dose group and 594 +/- 439 microg (young) and 730 +/- 551 microg (elderly) in the control group. The duration of fever in 1 cycle of chemotherapy was 0.3 +/- 1.0 days (young) and 0.1 +/- 0.8 days (elderly) in the low-dose group and 0.5 +/- 1.3 days (young) and 0.8 +/- 2.0 days (elderly) in the control group. A THP-COP regimen with low-dose G-CSF could be administered to NHL patients with safety. Administration of a 50-microg dose of lenograstim is sufficient and recommended for the treatment of NHL.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Linfoma não Hodgkin/tratamento farmacológico , Neutropenia/tratamento farmacológico , Adjuvantes Imunológicos/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Custos e Análise de Custo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/economia , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Doxorrubicina/economia , Feminino , Fator Estimulador de Colônias de Granulócitos/economia , Humanos , Lenograstim , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/economia , Masculino , Pessoa de Meia-Idade , Neutropenia/economia , Neutropenia/etiologia , Prednisolona/administração & dosagem , Prednisolona/economia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/economia , Estudos Retrospectivos , Vincristina/administração & dosagem , Vincristina/economiaRESUMO
We investigated whether immunosuppressive therapy using methylprednisolone (mPSL) with or without cyclosporin A (CsA) could benefit patients with myelodysplastic syndrome (MDS). Eligibility criteria for this study were a clinical diagnosis of MDS with less than 5% blast in peripheral blood, less than 10% blast in bone marrow and advanced cytopenia. Among 73 patients with MDS, 18 eligible and consecutive patients (8 men and 10 women), aged 48 to 87 years (median: 66.5 years) were assigned to receive mPSL pulse therapy (1,000 mg daily for 3 consecutive days, followed by tapering oral prednisolone; n= 12) or mPSL pulse with CsA therapy (4 to 5 mg/kg administered twice daily; n= 6). Six of 18 patients (33.3%; 3 of 10 patients with RA, 2 of 6 patients with RAEB, 1 of 2 patients with CMMoL) responded to immunosuppressive therapy. Four patients responded to mPSL pulse alone, and two patients responded to mPSL pulse with CsA. One of 6 patients with hypocellular bone marrow and 5 of 12 patients with normocellular or hypercellular marrow responded to immunosuppressive therapy. No patient with myelofibrosis responded to the therapy. The duration of response ranged from 4 to 59 months (median: 14 months). Although a significant difference was observed between responders and nonresponders in the survival rate ( P<0.05), no significant difference was found in clinical characteristics at entry between responders and nonresponders. In responders, mean hemoglobin levels were significantly increased ( P<0.01), and the required red cell transfusion dose was significantly reduced ( P<0.01). It is possible that immunosuppressive therapy might be effective for a certain subset of patients with MDS.
Assuntos
Ciclosporina/administração & dosagem , Imunossupressores/uso terapêutico , Metilprednisolona/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Hemoglobinas/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Masculino , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Pulsoterapia , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To compare the efficacy and safety of a biweekly CHOP regimen consisting of cyclophosphamide (CPA), doxorubicin (DOX), vincristine (VCR), and prednisolone (PSL) and those of a biweekly THP-COP regimen containing pirarubicin (THP), an anthracyclin with less cardiotoxicity than DOX. METHODS: A prospective, randomized phase II study with 80 patients (40 receiving CHOP or THP-COP) less than 70 years of age with previously untreated aggressive non-Hodgkin's lymphoma (NHL). The regimens consisted of DOX or THP 50 mg/m2, CPA 750 mg/m2, VCR 1.4 mg/m2, and PSL 100 mg/body administered for 5 days every 2 weeks for eight cycles. RESULTS: No significant differences in known prognostic factors were found between the two groups. Complete remission rate was 72.5% (72.5% for CHOP, 72.5% for THP-COP). The 5-year overall survival rate was 49.2% (43.7% for CHOP, 54.0% for THP-COP). When the patients were divided into groups with favorable or poor prognostic factors according to the International Prognostic Index, survival of the former group (L/LI) was superior to that of the later group (HI/H), regardless of chemotherapy regimen ( P < 0.001). Although grade 3 cardiotoxicity occurred in one patient in the CHOP group, no fatal toxic reactions occurred in either group. The THP-COP produced results equivalent to those of CHOP regarding efficacy and safety in aggressive NHL patients less than 70 years of age. CONCLUSIONS: Although both regimens effectively treated those patients with favorable prognostic factors, neither was satisfactory for treating those with poor prognostic factors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Esquema de Medicação , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Prognóstico , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
A 24-year-old man was admitted with fever and rhinostenosis. A bulky mass was observed in his left nasal cavity. A biopsy showed diffuse proliferation of large atypical lymphocytes, which were positive for CD45RO, CD56, MIB-1, and EBER. Bone marrow aspiration showed many histiocytes with active hemophagocytosis. A diagnosis of nasal NK cell lymphoma with hemophagocytic syndrome (clinical stage IVB) was made. Following CHOP regimen chemotherapy, the tumor transiently reduced in size, but the patient developed multiple organ failure possibly due to tumor lysis syndrome. His general condition was improved by intensive supporting therapy. Two weeks later, the tumor again got worse. Despite salvage chemotherapy with a P-IMVP16/CBDCA regimen, the patient died of multiple organ failure due to tumor lysis syndrome. Autopsy revealed diffuse necrosis and fibrosis without proliferation of lymphoma cells in the liver, spleen, bone marrow, and lymph nodes. During the clinical course, hypercytokinemia including soluble IL-2 receptor, interferon-gamma and IL-18 was observed. The poor prognosis of NK/T cell lymphoma might be associated with massive tissue damage with hypercytokinemia.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Histiocitose de Células não Langerhans/etiologia , Células Matadoras Naturais , Linfoma de Células T/tratamento farmacológico , Neoplasias Nasais/tratamento farmacológico , Prednisona/efeitos adversos , Síndrome de Lise Tumoral/etiologia , Vincristina/efeitos adversos , Adulto , Humanos , Linfoma de Células T/patologia , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Cavidade Nasal/patologia , Neoplasias Nasais/patologiaRESUMO
Niemann-Pick disease, type C (NPC) is a neurometabolic genetic disorder that is distinguished from other types of Niemann-Pick disease by its later onset, more insidious progression, variable visceromegaly, and abnormalities of intracellular cholesterol metabolism. We report cases in 18-year-old and 20-year-old brothers who presented with disinhibition and involuntary movement of their hands. Both brothers presented various signs such as dementia, vertical supranuclear ophthalmoplegia (VSO), dysarthria, axial and limb dystonia, hyperreflexia, pathologic reflex, cerebellar ataxia, as reported. They also presented startle response. Brain MRI showed diffuse cerebral atrophy and abdominal CT reveals hepato-splenomegaly in both patients. These cases were suspected to be NPC based on dementia, VSO, cerebellar ataxia, hepato-splenomegaly and foam cells in the bone marrow. Generally, the diagnosis of NPC is based on deficient cholesterol esterification and excessive lysosomal filipin staining in cultured skin fibroblasts. However, culture of fibroblasts obtained from a biopsied skin samples is slow. We have rapidly made the diagnosis of NPC in our patients by filipin staining of foam cells from bone marrow. This diagnostic process using a bone marrow smear is more convenient and rapid than previous methods using cultured skin fibroblasts.