RESUMO
Outcome of HIV-infected patients with AIDS-related lymphomas has improved during recent years. However, data on incidence, risk factors, and outcome of relapses in AIDS-related lymphomas after achieving complete remission are still limited. This prospective observational multicenter study includes HIV-infected patients with biopsy- or cytology-proven malignant lymphomas since 2005. Data on HIV infection and lymphoma characteristics, treatment and outcome were recorded. For this analysis, AIDS-related lymphomas patients in complete remission were analyzed in terms of their relapse- free survival and potential risk factors for relapses. In total, 254 of 399 (63.7%) patients with AIDS-related lymphomas reached a complete remission with their first-line chemotherapy. After a median follow up of 4.6 years, 5-year overall survival of the 254 patients was 87.8% (Standard Error 3.1%). Twenty-nine patients relapsed (11.4%). Several factors were independently associated with a higher relapse rate, including an unclassifiable histology, a stage III or IV according to the Ann Arbor Staging System, no concomitant combined antiretroviral therapy during chemotherapy and R-CHOP-based compared to more intensive chemotherapy regimens in Burkitt lymphomas. In conclusion, complete remission and relapse rates observed in our study are similar to those reported in HIV-negative non-Hodgkin lymphomas. These data provide further evidence for the use of concomitant combined antiretroviral therapy during chemotherapy and a benefit from more intensive chemotherapy regimens in Burkitt lymphomas. Modifications to the chemotherapy regimen appear to have only a limited impact on relapse rate.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/induzido quimicamente , Recidiva Local de Neoplasia/epidemiologia , Adulto , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Incidência , Linfoma Relacionado a AIDS/patologia , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Indução de Remissão , Fatores de Risco , Taxa de SobrevidaRESUMO
AIDS-related aggressive B cell lymphoma (HIV-NHL) is the second most common HIV-associated malignancy. In contrast, Hodgkin-lymphoma (HL) is one of the most common non-AIDS-defining malignancies. Current evidence-based recommendations for the treatment of HIV-associated lymphoma (HIV-lymphoma) are not available. A panel of experts in the field of HIV-related lymphoma performed literature searches of the PubMed, Medline, and Cochrane databases. The consensus process was carried out as an e-mail and meeting-based discussion group. Six cycles of R-CHOP or R-EPOCH are standard of care for patients (pts) with diffuse large B cell lymphoma (DLBCL). Pts with Burkitt lymphoma and good performance status should receive dose-intensive regimens such as the GMALL B-ALL/NHL protocol. Standard therapy has not been defined for pts with plasmablastic and primary effusion lymphoma. Pts with lymphoma in sensitive relapse should receive high-dose chemotherapy followed by autologous stem cell transplantation. Stage- and risk adapted treatment yields high remission and survival rates in pts with HIV-HL similar to those achieved in HIV-negative HL pts. Combination antiretroviral therapy (cART) should be applied concurrently to chemotherapy provided that pharmacokinetic interactions are being considered. Pts with HIV-lymphoma should usually be treated in an identical manner to HIV-negative patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Relacionado a AIDS/tratamento farmacológico , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Antibioticoprofilaxia , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Terapia Antirretroviral de Alta Atividade , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Interações Medicamentosas , Etoposídeo/administração & dosagem , Infecções por HIV/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma Relacionado a AIDS/radioterapia , Linfoma Relacionado a AIDS/cirurgia , Metotrexato/administração & dosagem , Estadiamento de Neoplasias , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Radioterapia Adjuvante , Medição de Risco , Rituximab , Vincristina/administração & dosagemRESUMO
Results of a prospective study of stage-adapted treatment of human immunodeficiency virus (HIV)-associated Hodgkin lymphoma (HIV-HL) showed a 2-year overall survival (OS) of 90.7% with no significant difference between early favorable (EF), early unfavorable (EU), and advanced HL. Patients with EF HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy involved field (IF) radiation, those with EU HIV-HL received four cycles of ABVD or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) baseline + 30 Gy IF, and six to eight cycles of BEACOPP baseline were administered in advanced disease. The objective of the present analysis is to determine long-term outcomes of HIV-HL. Of 108 patients, 23 (21%) had EF HL, 14 (13%) had EU HL, and 71 (66%) had advanced-stage HL. After a median follow-up of 9.14 (range, 0-12.9) years, there were five primary refractory HL patients (5%) and 11 relapses (10%), of which seven were late relapses (>2 years). A second primary malignancy (SPM) occurred in 10 patients after a median of 7.3 years (range, 1.5-10.7) from HL diagnosis. The 10-year OS for patients with EF, EU, and advanced HL was 95.7%, 84.6%, and 76.1%, respectively. By multivariate analysis, Center for Disease Control and Prevention category C (hazard ratio [HR] 3.00, 95% confidence interval [CI]: 1.16-7.74, p = 0.023) and achievement of complete remission were significant for OS (HR 0.03, 95% CI: 0.01-0.08, p = 2.45 × 10-9). In conclusion, a stage-adapted treatment approach for HIV-HL is highly effective with long-term survival rates similar to those reported in HIV-uninfected HL. However, the risk for late relapse and SPM is significant.
RESUMO
BACKGROUND: Lung cancer is one of the most common non-AIDS-defining malignancies in HIV-infected patients. However, data on clinical outcome and prognostic factors are scarce. METHODS: This was a national German multicentre, retrospective cohort analysis of all cases of lung cancer seen in HIV-infected individuals from 2000 through 2010. Survival was analyzed with respect to the use of antiretroviral therapy (ART), specific lung cancer therapies, and other potential prognostic factors. RESULTS: A total of 72 patients (mean age 55.5 y, CD4 T-cells 383/µl) were evaluated in this analysis. At time of lung cancer diagnosis, 86% were on ART. Of these, 79% had undetectable HIV-1 RNA (< 50 copies/ml) for a mean duration of 4.0 y. All but 1 patient were current or former heavy smokers (mean 42 package y). The median estimated overall survival was 1.08 y, with a 2-y overall survival of 24%. The prognosis did not improve during the observation time. A limited lung cancer stage of I-IIIA was associated with better overall survival when compared with the advanced stages IIIb/IV (p = 0.0003). Other factors predictive of improved overall survival were better performance status, CD4 T-cells > 200/µl, and a non-intravenous drug use transmission risk for HIV. CONCLUSIONS: Currently, most cases of lung cancer occur in the setting of limited immune deficiency and a long-lasting viral suppression. As in HIV-negative cases, the clinical stage of lung cancer is highly predictive of survival, and long-term overall survival can only be achieved at the limited stages. The still high mortality underscores the importance of smoking cessation strategies in HIV-infected patients.
Assuntos
Infecções por HIV/complicações , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Wilms' tumor gene 1 (WT1) is gaining increasing attention as a therapeutic target molecule due to its common expression in acute leukemias and its involvement in cell proliferation. Here, we reported on WT1 messenger RNA expression levels at diagnosis in a series of 238 adult acute lymphoblastic leukemia (ALL) samples of various subtypes and clinical outcome. WT1 expression was found in 219 out of 238 ALL samples (92%). Compared to a cohort of acute myeloid leukemia patients, the median WT1 expression level in ALL was significantly lower with large variations among different ALL subgroups. Specifically, WT1 expression levels were low in mature B-ALL and highest in ALL cases with co-expression of myeloid markers, making it a useful therapeutic target molecule in adult ALL with the exception of mature B-ALL. Cox regression analysis, considering ALL phenotype as well as molecular-cytogenetic subsets, revealed no independent prognostic role of WT1 expression level for disease-free and overall survival.
Assuntos
Regulação Leucêmica da Expressão Gênica , Genes do Tumor de Wilms , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Proteínas WT1 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Imunofenotipagem , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Resultado do Tratamento , Proteínas WT1/genética , Proteínas WT1/metabolismo , Adulto JovemRESUMO
This study was performed to investigate hematotoxicity and occurrence of PPE in patients with high-grade non-Hodgkins lymphoma treated with a modified CHOP regimen (CLAOP), where doxorubicin had been substituted by a noncardiotoxic pegliposomal doxorubicin. An open-label phase I/IIa study was performed evaluating CLAOP21/20 with 20 mg/m(2) of pegliposomal doxorubicin every 21 days (12 patients), and a dose-dense filgrastim supported CLAOP14 regimen every 14 days with escalating doses of pegliposomal doxorubicin (24 patients) in elderly high-grade lymphoma patients or patients with comorbidity interfering with cardiac function. CLAOP21/20 was well tolerated. Hematotoxicity was similar to that reported with regular CHOP. In the CLAOP14 cohort, a pegliposomal doxorubicin dose of 25 mg/m(2) was associated with dose-limiting hematotoxicity, febrile episodes, and PPE. Both regimens were active with an overall response rate of 60% and 77%, respectively. The recommended dose of pegliposomal doxorubicin in the biweekly regimen for Phase II/III testing is 20 mg/m(2).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Filgrastim , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Coração/efeitos dos fármacos , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Proteínas Recombinantes , Vincristina/uso terapêuticoRESUMO
A gain-of-function mutation of c-kit is the crucial step in tumorigenesis of gastrointestinal stromal tumors (GIST). Imatinib can block the activated receptor tyrosine kinase activity of c-kit. These findings made GIST an ideal candidate for evaluation of new targeted therapeutic approaches. Clinical studies demonstrated that, with imatinib, objective responses can be reached in more than 50% of patients with advanced GIST. Furthermore, even in those patients with stable disease, long-term tumor control could be achieved. Therefore imatinib at a dose of 400 mg/day is now the standard treatment of advanced GIST in which RO-resection cannot be reached. As imatinib resistance in GIST occurs at a median of 18 to 26 months, further targeted therapies have been explored. Sunitinib, another tyrosine kinase inhibitor, seems to be useful especially in patients with exon 9 mutations of c-kit, who usually have a worse response to imatinib. This might indicate that more exactly targeted therapies in GIST might improve clinical outcomes in the future.
Assuntos
Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-kit/efeitos dos fármacos , Pirimidinas/uso terapêutico , Antineoplásicos/farmacologia , Benzamidas , Resistencia a Medicamentos Antineoplásicos , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas c-kit/genética , Pirimidinas/farmacologia , Pirróis/uso terapêutico , SunitinibeRESUMO
Lung cancer (LC) is one of the most common non-AIDS (acquired immune deficiency syndrome)-defining malignancies. It occurs more frequently in persons living with human immunodeficiency virus (PLWHIV) than in the HIV-negative population. Compared to their HIV-negative counterparts, patients are usually younger and diagnosed at more advanced stages. The pathogenesis of LC in PLWHIV is not fully understood, but immunosuppression in combination with chronic infection and the oncogenic effects of smoking and HIV itself all seem to play a role. Currently, no established preventive screening is available, making smoking cessation the most promising preventive measure. Treatment protocols and standards are the same as for the general population. Notably, immuno-oncology will also become standard of care in a significant subset of HIV-infected patients with LC. As drug interactions and hematological toxicity must be taken into account, a multidisciplinary approach should include a physician experienced in the treatment of HIV. Only limited data is available on novel targeted therapies and checkpoint inhibitors in the setting of HIV.
Assuntos
Síndrome da Imunodeficiência Adquirida/diagnóstico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Antirretrovirais/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/etiologia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Medicina Baseada em Evidências , Humanos , Neoplasias Pulmonares/etiologia , Oncologia/normas , Guias de Prática Clínica como Assunto , Resultado do TratamentoRESUMO
In-vitro synergy of treosulfan and gemcitabine has been observed in chemotherapy-resistant tumours. This trial investigated the efficacy of gemcitabine plus treosulfan in metastatic uveal melanoma. Patients received 1000 mg/m of gemcitabine and treosulfan at a dose of 2500 or 3000 mg/m2 in cohort 1 and 3500 or 4000 mg/m2 in cohort 2. Chemotherapy was administered on days 1 and 8 every 4 weeks. Thirty-three patients were treated, 14 in cohort 1 and 19 in cohort 2. In cohort 1 with a treosulfan dose of
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Melanoma/tratamento farmacológico , Neoplasias Uveais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/análogos & derivados , Estudos de Coortes , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sobrevida , Resultado do Tratamento , Neoplasias Uveais/patologia , GencitabinaRESUMO
BACKGROUND: Vinorelbine was added to carboplatin plus paclitaxel to determine efficacy and toxicity in non-small cell lung cancer (NSCLC) patients with good performance status. PATIENTS AND METHODS: Vinorelbine 30 mg/m2 plus paclitaxel 175 mg/m2 plus carboplatin AUC 5 was administered every three weeks for a maximum of 6 cycles. RESULTS: One out of 37 patients had a complete and 12 a partial remission (35% response rate). Six patients (16%) had disease stabilization and 18 (49%) progressed. Grade III or IV neutropenia occurred in 11 (30%) and febrile neutropenia in 6 (16%) patients. Grade III/IV neuropathy was observed in 6 (16%) patients. The median time to progression was 6 months (95% CI 4.0 - 8.0), and median survival 11 months (95% CI 8.3 - 13.7). One- and two-year survival was 41% (95% CI 24 - 58) and 24% (95% CI 8.7 - 39.1), respectively. CONCLUSION: This triple-chemotherapy combination is feasible. The response rates justify further investigation in similar patient subgroups.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/administração & dosagem , Vimblastina/análogos & derivados , Vimblastina/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Taxa de Sobrevida , Fatores de Tempo , VinorelbinaRESUMO
This trial was performed to define the maximum tolerated dose (MTD) of treosulfan administered in combination with a fixed dose of gemcitabine in uveal melanoma patients. Preclinical studies suggested synergistic activity against uveal melanoma. Gemcitabine (1 g/m2) and treosulfan (2.5-4 g/m2) were administered on days 1 and 8, and cycles were repeated on day 29 for a maximum of six cycles. For treosulfan, dose escalation cohorts of 2-4 patients were enrolled. An additional 25 patients were entered at treosulfan dose levels II (3 g/m2) and III (3.5 g/m2). Thirty three patients with uveal melanoma and six patients with other histologies were accrued. Side-effects were predominantly haematological. The MTD was 3.5 g/m2 of treosulfan together with 1 g/m2 of gemcitabine. In the uveal melanoma patients, one partial response (PR) and 15 stablisations of disease (SD) were recorded and whether this translates into a survival gain should be explored further.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/análogos & derivados , Desoxicitidina/análogos & derivados , Melanoma/tratamento farmacológico , Neoplasias Uveais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Resultado do Tratamento , GencitabinaRESUMO
The Wilms tumor gene (WT1) is expressed in blasts of patients with acute leukemia, irrespective of lineage, and WT1 nuclear protein is detectable in the majority of such blasts. Only very few physiologic hematopoietic progenitors express WT1, but the WT1 expression level of these progenitors and that of leukemic blasts are comparable. Although not specific for acute hematologic malignant diseases, continuous WT1 expression in almost all leukemic blasts strikingly contrasts to its rather transient expression in very few physiologic hematopoietic progenitors. Quantitative and semiquantitative WT1 reverse transcriptase polymerase chain reaction (RT-PCR) protocols have limitations in discriminating physiologic from pathologic overall WT1 expression levels in mononuclear cell preparations. Because of these limitations, reports conflict on the usefulness of long-term monitoring of WT1 expression in patients with acute leukemia. Real-time quantitative WT1 RT-PCR protocols, however, have been developed and tested in small series of patients with acute leukemia. Such protocols hold promise to enable evaluation of the individual treatment response (short-term monitoring) and early diagnosis of imminent relapse through the detection and long-term monitoring of minimal residual disease in patients with acute leukemia. These protocols also should facilitate the notoriously difficult distinction between eosinophilic leukemia and hypereosinophilic syndromes. Data on WT1 expression in leukemic blasts and their physiologic counterparts are discussed in light of clinical relevance.
Assuntos
Biomarcadores Tumorais/análise , Leucemia/diagnóstico , Proteínas WT1/metabolismo , Humanos , Leucemia/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas WT1/genéticaRESUMO
PURPOSE: Although the outcome of patients with HIV-related Hodgkin lymphoma (HIV-HL) has markedly improved since the introduction of combined antiretroviral therapy, standard therapy is still poorly defined. This prospective study investigates a stage- and risk-adapted treatment strategy in patients with HIV-HL. PATIENTS AND METHODS: Patients with early favorable HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of involved-field (IF) radiation. In patients with early unfavorable HIV-HL, four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP baseline) or four cycles of ABVD + 30 Gy of IF radiation were administered. Six to eight cycles of BEACOPP baseline were given in patients with advanced-stage HIV-HL. In patients with advanced HIV infection, BEACOPP was replaced with ABVD. RESULTS: Of 108 patients (including eight female patients) included in the study, 23 (21%) had early favorable HL, 14 (13%) had early unfavorable HL, and 71 (66%) had advanced-stage HL. The median CD4 count at HL diagnosis was 240/µL. The complete remission rates for patients with early favorable, early unfavorable, and advanced-stage HL were 96%, 100%, and 86%, respectively. The 2-year progression-free survival of the entire study population was 91.7%. Eleven patients (11%) have died, and treatment-related mortality was 5.6%. The 2-year overall survival rate was 90.7% with no significant difference between early favorable (95.7%), early unfavorable (100%), and advanced-stage HL (86.8%). CONCLUSION: In patients with HIV-HL, stage- and risk-adapted treatment is feasible and effective. The prognosis for patients with HIV-HL may approach that of HIV-negative patients with HL.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções por HIV/complicações , Doença de Hodgkin/tratamento farmacológico , Linfoma Relacionado a AIDS/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Humanos , Linfoma Relacionado a AIDS/patologia , Linfoma Relacionado a AIDS/radioterapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Prognóstico , Estudos Prospectivos , Indução de Remissão , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: AIDS-related lymphomas (ARLs) significantly contribute to mortality in HIV-infected patients. Optimal chemotherapy treatment and the use of rituximab remain controversial. The aim of the present cohort study was to analyze the outcome of HIV-infected patients diagnosed with ARL, with regard to the use of rituximab, clinical characteristics and histopathological markers. METHODS AND DESIGN: This observational uncontrolled multicenter cohort study included 163 HIV-infected patients with ARL diagnosed between January 2005 and December 2008 in Germany. RESULTS: Patients with CD20-positive ARL had a significantly better overall survival (OS) and progression-free survival (PFS) than patients with CD20-negative ARL [hazard ratio 0.28, 95% confidence interval (CI) 0.15-0.53 and hazard ratio 0.29, 95% CI 0.16-0.53]. In CD20-positive cases, the use of rituximab was associated with better OS and PFS (n = 128, hazard ratio 0.48, 95% CI 0.25-0.93 and hazard ratio 0.47, 95% CI 0.26-0.86), even in patients with severe immune deficiency at ARL diagnosis (CD4 T-cell count<100 cells/µl, n = 33; OS: hazard ratio 0.25, 95% CI 0.07-0.90). In multivariate analysis, CD4 T-cell counts more than 100 cells/µl and the use of rituximab were associated with better OS and PFS. In total, there were 12 polychemotherapy-associated deaths, which were not related to specific therapy regimens or to the use of rituximab. CONCLUSION: In patients with CD20-positive ARL, CD4 T-cell count at ARL diagnosis and the use of rituximab had strong impact on survival. Rituximab was beneficial in ARL even in the setting of severe immune deficiency and was not associated with an increased risk of fatal infections.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Antígenos CD20/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Hospedeiro Imunocomprometido , Linfoma Relacionado a AIDS/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/imunologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Adulto , Idoso , Anticorpos Monoclonais Murinos/farmacologia , Antígenos CD20/metabolismo , Antineoplásicos/farmacologia , Terapia Antirretroviral de Alta Atividade , Biomarcadores Tumorais/metabolismo , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/metabolismo , Estudos de Coortes , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Linfoma Relacionado a AIDS/imunologia , Linfoma Relacionado a AIDS/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Rituximab , Adulto JovemRESUMO
BACKGROUND: The anthracycline/ifosfamide combination is the most effective chemotherapy in soft tissue sarcoma. To improve the tolerability and potential efficacy of this combination, the authors combined a moderate dose of continuous infusion ifosfamide with liposomal daunorubicin (L-Dauno). METHODS: In a single-arm, Phase II study, 40 patients with a median age of 57 years (range, 19-78 years) were enrolled. Of these, 35 patients were treated with first-line chemotherapy. The treatment regimen was comprised of ifosfamide at a dose of 5 g/m(2) over 24 hours and L-Dauno at a dose of 100 mg/m(2) every 4 weeks with granulocyte-colony-stimulating factor support. RESULTS: Eleven (31%) of 35 anthracycline/ifosfamide-naive patients achieved a partial/complete response, 6 patients (17%) had stable disease, and 13 patients (37%) had disease progression. Three patients were not evaluable, and there were two intermittent deaths. The median time to disease progression was 6 months, the median overall survival was 14 months, and the median time to treatment failure was 15 months. Toxicity was tolerable. CONCLUSIONS: The combination of Ifosfamide and L-Dauno was found to be a highly active chemotherapy regimen for first-line treatment of soft tissue sarcoma. Therefore, we believe randomized studies with this regimen are warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Daunorrubicina/administração & dosagem , Progressão da Doença , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Ifosfamida/administração & dosagem , Infusões Intravenosas , Lipossomos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Sarcoma/patologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
WT1 is a transcription factor involved in differentiation and proliferation of acute myeloid leukemia (AML) blasts and is expressed in 90% of cases, as determined by nested reverse transcription polymerase chain reaction (RT-PCR). It is proposed to be a key molecule in leukemia promotion. To assess the relevance of WT1 expression, we analyzed blood and bone marrow samples from 58 AML patients (37 at diagnosis, 8 in hematological remission, and 13 at relapse) for the level of WT1 expression, using quantitative real-time RT-PCR. In addition, 21 randomly chosen samples were also analyzed for the quantitative expression of the main WT1 splice variants. As expected, samples from patients at the time of diagnosis or relapse showed significantly higher WT1 expression compared to samples from patients in remission or control samples. No striking difference in expression levels was found between various French-American-British (FAB) subtypes. The level of WT1 expression observed in patients at the time of initial diagnosis was similarly high in patients at relapse. Expression of the four main isoforms (E5+/KTS+, E5-/KTS+, E5+/KTS-, and E5-/KTS-) was found in all samples with significantly higher expression levels of the E5+ variants. Together, these findings support the potential of WT1 as a target for novel treatment approaches in AML.
Assuntos
Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Splicing de RNA/genética , RNA Neoplásico/genética , Proteínas WT1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Diferenciação Celular/genética , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Neoplásico/sangue , Recidiva , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteínas WT1/metabolismoRESUMO
Overexpression of the embryonic transcription factor, Wilms' tumour protein 1 (WT1), is common in acute myeloid leukaemias (AML). Mutations of Wilms' tumour gene 1 (WT1) in AML are rare and WT1 expression may be increased by other transcription factors. PAX2, PAX8 and GATA-1 are known physiological regulators of WT1. In the present study, we analysed either bone marrow or blood samples of 43 AML patients for the expression levels of WT1, PAX2, PAX8 and GATA-1 by real-time reverse transcription polymerase chain reaction (LightCycler). Bone marrow samples of patients without haematological malignancies and stem cell preparation samples from healthy donors and lymphoma patients served as controls. PAX2 expression was found in 11 of 43 AML samples, with a clear correlation of PAX2 with WT1 expression levels observed. PAX8 expression was found in two additional samples. GATA-1 expression was detectable in 41 of 43 AML samples and also in all control samples; no significant differences between these groups were observed and no correlation of GATA-1 expression with WT1 expression levels was apparent. In conclusion, PAX2, and possibly PAX8, appears to be a candidate for the upregulation of WT1 in a proportion of AML, whereas GATA-1 expression cannot be explained as an inducer of WT1. In two-thirds of leukaemias from our series, the basis of WT1 upregulation cannot be explained by the simple upregulation of the known WT1 activators.