RESUMO
Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFNâº) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Interferon-alfa/efeitos adversos , Infecções Fúngicas Invasivas/etiologia , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Zidovudina/efeitos adversos , Adolescente , Adulto , Idoso , Antibioticoprofilaxia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aspergilose/epidemiologia , Aspergilose/etiologia , Neutropenia Febril/complicações , Feminino , Febre de Causa Desconhecida/epidemiologia , Febre de Causa Desconhecida/etiologia , Fungemia/epidemiologia , Fungemia/etiologia , Humanos , Interferon-alfa/administração & dosagem , Infecções Fúngicas Invasivas/epidemiologia , Estimativa de Kaplan-Meier , Leucemia-Linfoma de Células T do Adulto/complicações , Leucemia-Linfoma de Células T do Adulto/mortalidade , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/etiologia , Pneumonia por Pneumocystis/epidemiologia , Pneumonia por Pneumocystis/etiologia , Prevalência , Prognóstico , Estudos Retrospectivos , Estrongiloidíase/epidemiologia , Estrongiloidíase/etiologia , Estrongiloidíase/prevenção & controle , Resultado do Tratamento , Adulto Jovem , Zidovudina/administração & dosagemRESUMO
Human endogenous retroviruses (HERVs) are retroviral sequences integrated into 8% of the human genome resulting from ancient exogenous retroviral infections. Unlike endogenous retroviruses of other mammalian species, HERVs are mostly replication and retro-transposition defective, and their transcription is strictly regulated by epigenetic mechanisms in normal cells. A significant addition to the growing body of research reveals that HERVs' aberrant activation is often associated with offsetting diseases like autoimmunity, neurodegenerative diseases, cancers, and chemoresistance. Adult T-cell leukemia/lymphoma (ATLL) is a very aggressive and chemoresistant leukemia caused by the human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATLL remains poor despite several new agents being approved in the last few years. In the present study, we compare the expression of HERV genes in CD8+-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. Herein, we show that HERVs are highly upregulated in acute ATLL. Our results further demonstrate that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the exciting possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology.
Assuntos
Retrovirus Endógenos , Leucemia-Linfoma de Células T do Adulto , Humanos , Leucemia-Linfoma de Células T do Adulto/virologia , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/patologia , Leucemia-Linfoma de Células T do Adulto/metabolismo , Retrovirus Endógenos/genética , Retrovirus Endógenos/metabolismo , Vírus Linfotrópico T Tipo 1 Humano/genética , Sequências Repetidas Terminais/genética , Produtos do Gene env/metabolismo , Produtos do Gene env/genéticaRESUMO
BACKGROUND: There is limited information regarding the efficacy and long term safety of intrathecal injection of liposomal cytarabine in leukemic or lymphomatous meningitis. DESIGN AND METHODS: We studied 20 consecutive HIV-negative patients with leukemic or lymphomatous meningitis who were treated with intrathecal liposomal cytarabine between 2004 and 2007. We focused on efficacy and on any late effects of the drug. RESULTS: Twenty patients who received intrathecal liposomal cytarabine injection as part of their treatment; of these, 9 were alive and in complete remission at the end of the study. Median survival from the time of the first injection was 22.7 months (range, 0.5 to 64 months). Short-term toxicity related to intrathecal of liposomal cytarabine was observed in 2 cases; headache in 1 case and regressive facial palsy and diplopy in 1 case. Long-term toxicity was seen in 2 cases; clinical symptoms were urinary and fecal dysfunction with confusion in 1 case, and urinary dysfunction in 1 case. Both patients had been heavily pre-treated with neurotoxic drugs and neuraxis irradiation. CONCLUSION: In our experience, intrathecal liposomal cytarabine injections were convenient in the management of leukemic and lymphomatous meningitis, and can lead to long-term survival. Although neurotoxicity was rare, clinicians should exercise caution when retreatment is required in relapsing patients.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Citarabina/administração & dosagem , Feminino , Humanos , Injeções Espinhais , Lipossomos/química , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
For the last ten years, non-Aspergillus mold species have been increasingly involved in human invasive infections, probably as a consequence of more intense immunosuppression and prolonged patient survival, and of selective pressure since antifungal agents are currently used for prophylaxis or therapy. Scedosporium prolificans, one of these emerging fungi, has been isolated in a broad spectrum of clinical presentations in humans, including respiratory-tract colonization, superficial or locally invasive infections, and disseminated infections in immunocompromised patients. Here, we report the recent emergence of invasive infections due to S. prolificans in France, and describe four new cases diagnosed during the last six years. Only one disseminated scedosporiosis has been reported before this in France, in 1994. Three out of our four cases were breakthrough infections in immunocompromised patients receiving posaconazole or voriconazole therapy. The aims of the present review were thus to gain a better understanding of scedosporiosis epidemiology and clinical features, and to review recent advances in multimodal management of these infections, including surgery, recovery and/or enhancement of immunity, and antifungal combinations, especially voriconazole plus terbinafine.
Assuntos
Micoses/epidemiologia , Micoses/microbiologia , Scedosporium/isolamento & purificação , Adulto , Idoso , Animais , França/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Micoses/tratamento farmacológico , Micoses/cirurgiaAssuntos
Sangue Fetal , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco de Sangue Periférico , Doadores de Sangue , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Família , Sangue Fetal/citologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/sangue , Doença de Hodgkin/terapia , Humanos , Indução de Remissão , Terapia de Salvação , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: While patients with early-stage Hodgkin lymphoma (HL) have an excellent outcome with combined treatment, the radiation therapy (RT) dose and treatment with chemotherapy alone remain questionable. This noninferiority trial evaluates the feasibility of reducing the dose or omitting RT after chemotherapy. METHODS AND MATERIALS: Patients with untreated supradiaphragmatic HL without risk factors (age ≥ 50 years, 4 to 5 nodal areas involved, mediastinum-thoracic ratio ≥ 0.35, and erythrocyte sedimentation rate ≥ 50 mm in first hour without B symptoms or erythrocyte sedimentation rate ≥ 30 mm in first hour with B symptoms) were eligible for the trial. Patients in complete remission after chemotherapy were randomized to no RT, low-dose RT (20 Gy in 10 fractions), or standard-dose involved-field RT (36 Gy in 18 fractions). The limit of noninferiority was 10% for the difference between 5-year relapse-free survival (RFS) estimates. From September 1998 to May 2004, 783 patients received 6 cycles of epirubicin, bleomycin, vinblastine, and prednisone; 592 achieved complete remission or unconfirmed complete remission, of whom 578 were randomized to receive 36 Gy (n=239), 20 Gy of involved-field RT (n=209), or no RT (n=130). RESULTS: Randomization to the no-RT arm was prematurely stopped (≥20% rate of inacceptable events: toxicity, treatment modification, early relapse, or death). Results in the 20-Gy arm (5-year RFS, 84.2%) were not inferior to those in the 36-Gy arm (5-year RFS, 88.6%) (difference, 4.4%; 90% confidence interval [CI] -1.2% to 9.9%). A difference of 16.5% (90% CI 8.0%-25.0%) in 5-year RFS estimates was observed between the no-RT arm (69.8%) and the 36-Gy arm (86.3%); the hazard ratio was 2.55 (95% CI 1.44-4.53; P<.001). The 5-year overall survival estimates ranged from 97% to 99%. CONCLUSIONS: In adult patients with early-stage HL without risk factors in complete remission after epirubicin, bleomycin, vinblastine, and prednisone chemotherapy, the RT dose may be limited to 20 Gy without compromising disease control. Omitting RT in these patients may jeopardize the treatment outcome.