RESUMO
A 44-year-old HIV-positive man diagnosed with diffuse large B-cell lymphoma in 2021 achieved complete remission with six cycles of R-CHOP therapy but had a relapse in November 2022. ESHAP therapy failed to induce remission, leading to complete remission with four cycles of Pola-BR therapy. Post-failure of autologous stem cell harvest, cord blood transplantation (CBT) was performed in June 2023. Notably, this case used recently approved intramuscular antiretroviral therapy (ART) with cabotegravir and rilpivirine, addressing gastrointestinal complications during CBT. This innovative use of intramuscular ART in the treatment of malignancy represents a first in the field, offering a pioneering approach to HIV-related lymphoma.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por HIV , Linfoma Difuso de Grandes Células B , Humanos , Masculino , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Injeções Intramusculares , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Antirretrovirais/uso terapêutico , Antirretrovirais/administração & dosagemRESUMO
We report a first in-depth comparison of immune reconstitution in patients with HIV-related lymphoma following autologous hematopoietic cell transplant (AHCT) recipients (n=37, lymphoma, BEAM conditioning), HIV(-) AHCT recipients (n=30, myeloma, melphalan conditioning) at 56, 180, and 365 days post-AHCT, and 71 healthy control subjects. Principal component analysis showed that immune cell composition in HIV(+) and HIV(-) AHCT recipients clustered away from healthy controls and from each other at each time point, but approached healthy controls over time. Unsupervised feature importance score analysis identified activated T cells, cytotoxic memory and effector T cells [higher in HIV(+)], and naïve and memory T helper cells [lower HIV(+)] as a having a significant impact on differences between HIV(+) AHCT recipient and healthy control lymphocyte composition (p<0.0033). HIV(+) AHCT recipients also demonstrated lower median absolute numbers of activated B cells and lower NK cell sub-populations, compared to healthy controls (p<0.0033) and HIV(-) AHCT recipients (p<0.006). HIV(+) patient T cells showed robust IFNγ production in response to HIV and EBV recall antigens. Overall, HIV(+) AHCT recipients, but not HIV(-) AHCT recipients, exhibited reconstitution of pro-inflammatory immune profiling that was consistent with that seen in patients with chronic HIV infection treated with antiretroviral regimens. Our results further support the use of AHCT in HIV(+) individuals with relapsed/refractory lymphoma.
Assuntos
Infecções por HIV/imunologia , Infecções por HIV/terapia , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune/imunologia , Linfoma Relacionado a AIDS/terapia , Ensaios Clínicos Fase II como Assunto , Humanos , Transplante Autólogo/métodosAssuntos
Linfoma Relacionado a AIDS/terapia , Linfoma de Efusão Primária/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gerenciamento Clínico , Feminino , Alemanha/epidemiologia , HIV-1/isolamento & purificação , Humanos , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/virologia , Linfoma de Efusão Primária/epidemiologia , Linfoma de Efusão Primária/virologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: This study investigates the effect of autologous bone marrow transfusion (BMT) on the reconstruction of both bone marrow and the immune system in patients with AIDS-related lymphoma (ARL). METHODS: A total of 32 patients with ARL participated in this study. Among them, 16 participants were treated with conventional surgery and chemotherapy (control group) and the remaining 16 patients were treated with chemotherapy followed by autologous bone marrow transfusion via a mesenteric vein (8 patients, ABM-MVI group) or a peripheral vein (8 patients, ABM-PI group). Subsequently, peripheral blood and lymphocyte data subsets were detected and documented in all patients. RESULTS: Before chemotherapy, no significant difference in indicators was observed between three groups of ARL patients. Unexpectedly, 2 weeks after the end of 6 courses of chemotherapy, the ABM-MVI group, and the ABM-PI group yielded an increased level of CD8+T lymphocytes, white blood cells (WBC), and platelet (PLT) in peripheral blood in comparison to the control group. Notably, the number of CD4+T lymphocytes in the ABM-PI group was significantly higher than that in the other two groups. Additionally, no significant difference in haemoglobin levels was observed before and after chemotherapy in both the ABM-MVI and ABM-PI groups, while haemoglobin levels in the control group decreased significantly following chemotherapy. CONCLUSIONS: Autologous bone marrow transfusion after chemotherapy can promote the reconstruction of both bone marrow and the immune system. There was no significant difference in bone marrow recovery and reconstruction between the mesenteric vein transfusion group and the peripheral vein transfusion group.
Assuntos
Medula Óssea/imunologia , Linfoma Relacionado a AIDS/terapia , Adulto , Idoso , Antirretrovirais/uso terapêutico , Contagem de Células Sanguíneas , Plaquetas/citologia , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas , Hemoglobinas/análise , Humanos , Leucócitos/citologia , Linfoma Relacionado a AIDS/imunologia , Linfoma Relacionado a AIDS/mortalidade , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Linfócitos T/citologia , Transplante Autólogo , Adulto JovemRESUMO
The MATRix chemoimmunotherapy regimen is highly effective in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL). However, nothing is known about its feasibility and efficacy in everyday practice, where patients are more often older/frailer than those enrolled in clinical trials. We conducted a retrospective study addressing tolerability/efficacy of MATRix in 156 consecutive patients with newly diagnosed PCNSL treated outside a clinical trial. Median age and ECOG Performance Status of considered patients were 62 years (range 28-78) and 2 (range 0-4). The overall response rate after MATRix was 79%. Nine (6%) treatment-related deaths were recorded. After a median follow-up of 27.4 months (95% confidence interval [CI] 24.4-31.9%), the two-year progression-free and overall survival were 56% (95% CI 48.4-64.9%) and 64.1% (95% CI 56.7-72.5%) respectively. Patients not eligible for the IELSG32 trial were treated with lower dose intensity and had substantially worse outcomes than those fulfilling inclusion criteria. This is the largest series of PCNSL patients treated with MATRix outside a trial and recapitulates the IELSG32 trial outcomes in the non-trial setting for patients who fit the trial criteria. These data underscore the feasibility and efficacy of MATRix as induction treatment for fit patients in routine practice.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/radioterapia , Terapia Combinada , Comorbidade , Quimioterapia de Consolidação , Irradiação Craniana , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Quimioterapia de Indução , Internacionalidade , Estimativa de Kaplan-Meier , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/radioterapia , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Transplante de Órgãos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/terapia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Tiotepa/administração & dosagem , Tiotepa/efeitos adversosRESUMO
The outcome of relapsed/refractory HIV-associated lymphoma remains poor, even in the era of combined antiretroviral therapy. However, recent reports showed the efficacy of autologous stem cell transplantation (ASCT). We conducted a single-arm, multicenter phase II study in patients with relapsed/refractory HIV-associated lymphoma to assess the safety and efficacy of ASCT. The study included 14 patients with relapsed/refractory HIV-associated lymphoma. Five patients who achieved partial remission or better after the standard salvage regimen proceeded to ASCT. Conditioning treatment involved ranimustine (300 mg/m2) on day - 6, etoposide (200 mg/m2) on days - 5 to - 3, cytarabine (200 mg/m2) on days - 5 to - 3, and L-PAM (140 mg/m2) on day - 2. All patients achieved engraftment and were alive on day 100 of ASCT. One-year and 2-year overall survival rates were both 40% and 1-year and 2-year progression-free survival rates were both 40%. Grade 2 or 3 diarrhea and oral mucositis were observed in 43% of patients. Cytomegalovirus antigenemia, retinitis, and bacterial infections were noted in 43%, 29%, and 29% of patients, respectively. Therapy-related death was not observed. Although the number of enrolled patients was insufficient for statistical analysis. ASCT was feasible and safe for relapsed/refractory HIV-associated lymphoma.Registration: This study is registered in UMIN-CTR (UMIN000003159).
Assuntos
Linfoma Relacionado a AIDS/terapia , Transplante de Células-Tronco de Sangue Periférico , Transplante Autólogo , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Estudos de Viabilidade , Humanos , Linfoma Relacionado a AIDS/mortalidade , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Compostos de Nitrosoureia/administração & dosagem , Segurança , Taxa de SobrevidaRESUMO
Individuals infected with human immunodeficiency virus (HIV) have higher morbidity and mortality due to cancer, which is the third most common cause of death in this group, despite the high effectiveness of antiretroviral therapy (ART). We describe the clinical and laboratory characteristics, initial staging and outcome of HIV-related lymphoma.We included 18 patients in the study, of whom 61.1% were male, mean age 41 years. Nine of the 18 patients (50%) had a diagnosis of HIV infection concurrent with the diagnosis of lymphoma.The most common histological types were diffuse non-Hodgkin B-cell lymphoma, 8 patients (44.4%); and Burkitt lymphoma, 5 (27.8%) cases. The Cotswold revision of the Ann Arbor staging classification in 14 patients (77.7%) was between III and IV. B Symptoms were present in 11 patients (61.1%), bulky mass was observed in 11 cases (61.1%) and had extra-nodal involvement in 8 patients (44.4%).Of the 18 cases analyzed, 8 followed on to second-line treatment, wherein the CODOX-M/IVAC scheme (cyclophosphamide, adriamycin, vincristine, methotrexate/ifosfamide, etoposide, and cytosine arabinoside) was used in 3 of the cases. The second most common scheme was etoposide, doxorubicin, vincristine and cyclophosphamide (EPOCH), used in 2 cases (25%), while in single cases (12.5% each) cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP), ifosfamide, etoposide, and carboplatin (ICE) and dexamethasone, cisplatin, and cytarabine (DHAP) were used.In this series, we observed very high mortality, equivalent to 44.4%, and a complete response in only 11.1%, much lower than that observed by other authors.We found that patients diagnosed with lymphoma associated with HIV had an advanced early clinical staging, and evolved with low response rates to chemotherapy.
Assuntos
Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/terapia , Adulto , Antineoplásicos/uso terapêutico , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/patologia , Linfoma de Burkitt/terapia , Feminino , Humanos , Linfoma Relacionado a AIDS/patologia , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
Cancer is the leading cause of death for HIV-infected persons in economically developed countries, even in the era of antiretroviral therapy (ART). Lymphomas remain a leading cause of cancer morbidity and mortality for HIV-infected patients and have increased incidence even in patients optimally treated with ART. Even limited interruptions of ART can lead to CD4 cell nadirs and HIV viremia, and increase the risk of lymphoma. The treatment of lymphoma is now similar for HIV-infected patients and the general population: patients with good HIV control can withstand intensive therapies appropriate to the lymphoma, including autologous and even allogeneic hematopoietic stem cell transplantation. Nonetheless, HIV-related lymphomas have unique aspects, including differences in lymphoma pathogenesis, driven by the presence of HIV, in addition to coinfection with oncogenic viruses. These differences might be exploited in the future to inform therapies. The relative incidences of lymphoma subtypes also differ in the HIV-infected population, and the propensity to advanced stage, aggressive presentation, and extranodal disease is higher. Other unique aspects include the need to avoid potential interactions between ART and chemotherapeutic agents, and the need for HIV-specific supportive care, such as infection prophylaxis. Despite these specific challenges for cancer treatment in the setting of HIV infection, the care of these patients has progressed sufficiently that recent guidelines from the American Society of Clinical Oncology advocate the inclusion of HIV-infected patients alongside HIV- patients in cancer clinical trials when appropriate.
Assuntos
Linfoma Relacionado a AIDS/terapia , Animais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Terapia Genética/métodos , HIV/efeitos dos fármacos , HIV/isolamento & purificação , Infecções por HIV/complicações , Infecções por HIV/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoterapia Adotiva/métodos , Linfoma Relacionado a AIDS/virologiaAssuntos
Neoplasias Hematológicas/epidemiologia , Academias e Institutos , Pesquisa Biomédica , Linfoma de Burkitt/epidemiologia , Linfoma de Burkitt/terapia , Fortalecimento Institucional , Educação Médica Continuada , Neoplasias Hematológicas/terapia , Humanos , Cooperação Internacional , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/terapia , Apoio à Pesquisa como Assunto , Uganda/epidemiologia , Estados UnidosRESUMO
BACKGROUND: HIV-associated lymphomas (HAL) remain an important cause of morbidity and mortality in HIV patients, especially in the setting of treatment-refractory disease. Hematopoietic cell transplantation (HCT) is considered a curative option for patients with refractory HAL. PATIENTS AND METHODS: We report the efficacy of autologous HCT in 20 patients with HAL [non-Hodgkin lymphoma = 14 (70%), Hodgkin lymphoma = 6 (30%)]. At the time of transplantation, the median peripheral blood CD4+ count was 226 cells/µL. HIV virus load was undetectable in 14 (70%) of 20 patients. RESULTS: The median follow-up of surviving patients was 47 months (range, 20-119 months). The median time to neutrophil engraftment was 11 days. The median progression-free survival and median overall survival have not been reached. At 4 years after transplantation, progression-free survival and overall survival were 65% and 70%, respectively. Six patients died from disease relapse or progression (n = 5) and infection (n = 1). Nonrelapse mortality was 0 and 5% at 100 days and 4 years after transplantation, respectively. CONCLUSION: Autologous HCT is an effective therapy for refractory/relapsed HAL with manageable toxicity, similar to non-HIV patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Linfoma Relacionado a AIDS/terapia , Linfoma não Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Progressão da Doença , Estudos de Viabilidade , Feminino , Florida , HIV/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/virologia , Humanos , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/mortalidade , Linfoma Relacionado a AIDS/virologia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/virologia , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transplante Autólogo , Carga ViralRESUMO
Plasmablastic lymphoma is a non-Hodgkin lymphoma characterized by its plasmacytic differentiation and predilection for the oral cavity. It is among the lymphomas most commonly associated with AIDS. This report details a case of a HIV-positive patient with a 1-month history of an exophytic mass in the gingival area of the upper left quadrant. The diagnosis of plasmablastic lymphoma was made based on its histopathological and immunophenotypical features. She was treated with chemotherapy followed by autologous hematopoietic stem cell transplantation. Despite complete resolution of the lesion, the patient died of cardiorespiratory arrest. This case illustrates plasmablastic lymphoma as the first clinical manifestation of AIDS, highlighting the importance of differentiating between a potentially malignant lesion and other pathologic processes.
Assuntos
Linfoma Relacionado a AIDS/patologia , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Linfoma Plasmablástico/patologia , Linfoma Plasmablástico/virologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/patologia , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Linfoma Relacionado a AIDS/terapia , Pessoa de Meia-Idade , Neoplasias Bucais/terapia , Linfoma Plasmablástico/terapiaAssuntos
Infecções por HIV/diagnóstico , Linfoma Relacionado a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Estudos Transversais , Fidelidade a Diretrizes , Infecções por HIV/epidemiologia , Infecções por HIV/patologia , Infecções por HIV/terapia , Humanos , Linfoma Relacionado a AIDS/epidemiologia , Linfoma Relacionado a AIDS/patologia , Linfoma Relacionado a AIDS/terapia , Estadiamento de Neoplasias , Prognóstico , RiscoRESUMO
BACKGROUND: The optimal therapeutic approach for patients with AIDS-related primary central nervous system lymphoma (AR-PCNSL) remains undefined. While its incidence declined substantially with combination antiretroviral therapy (cART), AR-PCNSL remains a highly aggressive neoplasm for which whole brain radiotherapy (WBRT) is considered a standard first-line intervention. METHODS: To identify therapy-related factors associated with favorable survival, we first retrospectively analyzed outcomes of AR-PCNSL patients treated at San Francisco General Hospital, a public hospital with a long history of dedicated care for patients with HIV and AIDS-related malignancies. Results were validated in a retrospective, multicenter analysis that evaluated all newly diagnosed patients with AR-PCNSL treated with cART plus high-dose methotrexate (HD-MTX). RESULTS: We provide evidence that CD4+ reconstitution with cART administered during HD-MTX correlates with long-term survival among patients with CD4 <100. This was confirmed in a multicenter analysis which demonstrated that integration of cART regimens with HD-MTX was generally well tolerated and resulted in longer progression-free survival than other treatments. No profound differences in immunophenotype were identified in an analysis of AR-PCNSL tumors that arose in the pre- versus post-cART eras. However, we detected evidence for a demographic shift, as the proportion of minority patients with AR-PCNSL increased since advent of cART. CONCLUSION: Long-term disease-free survival can be achieved in AR-PCNSL, even among those with histories of opportunistic infections, limited access to health care, and medical non-adherence. Given this, as well as the long-term toxicities of WBRT, we recommend that integration of cART plus first-line HD-MTX be considered for all patients with AR-PCNSL.
Assuntos
Antirretrovirais/uso terapêutico , Neoplasias do Sistema Nervoso Central/mortalidade , Irradiação Craniana , Linfoma Relacionado a AIDS/mortalidade , Metotrexato/uso terapêutico , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Linfoma Relacionado a AIDS/patologia , Linfoma Relacionado a AIDS/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Treatment outcomes for patients with HIV-related lymphoma have improved since the advent of combination antiretroviral therapy. Standard regimens, including intensive regimens, are being used with encouraging results in patients with diffuse large B-cell lymphoma, Burkitt lymphoma, Hodgkin lymphoma, and primary central nervous system lymphoma. Approaches to salvage therapy also parallel those used in patients without HIV infection, including autologous and allogeneic hematopoietic stem cell transplant. Drug interactions with particular antiretrovirals warrant close attention. At a population level, outcomes in patients with HIV infection and lymphoma remain inferior to outcomes achieved in the general population-but a great deal of progress has been made.
Assuntos
Linfoma Relacionado a AIDS/terapia , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Plasmablástico/tratamento farmacológico , Prednisona/uso terapêutico , Rituximab , Vincristina/uso terapêuticoRESUMO
Abstract Plasmablastic lymphoma is a non-Hodgkin lymphoma characterized by its plasmacytic differentiation and predilection for the oral cavity. It is among the lymphomas most commonly associated with AIDS. This report details a case of a HIV-positive patient with a 1-month history of an exophytic mass in the gingival area of the upper left quadrant. The diagnosis of plasmablastic lymphoma was made based on its histopathological and immunophenotypical features. She was treated with chemotherapy followed by autologous hematopoietic stem cell transplantation. Despite complete resolution of the lesion, the patient died of cardiorespiratory arrest. This case illustrates plasmablastic lymphoma as the first clinical manifestation of AIDS, highlighting the importance of differentiating between a potentially malignant lesion and other pathologic processes.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Linfoma Relacionado a AIDS/patologia , Linfoma Plasmablástico/patologia , Linfoma Plasmablástico/virologia , Biópsia , Neoplasias Bucais/terapia , Imuno-Histoquímica , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/patologia , Linfoma Relacionado a AIDS/terapia , Linfoma Plasmablástico/terapiaRESUMO
Plasmablastic lymphoma (PBL) is a rare AIDS-related malignancy with a poor prognosis. Little is known about this entity, and no standard treatment regimen has been defined. To establish an adequate treatment strategy, we investigated 24 cases of PBL arising in human immunodeficiency virus-positive individuals. Most of the patients were in the AIDS stage, with a median CD4 count of 67.5/µL. Lymph nodes (58 %), gastrointestinal tract (42 %), bone marrow (39 %), oral cavity (38 %), and CNS (18 %) were the most commonly involved sites. Histology findings for the following were positive at varying rates, as follows: CD10 (56 %); CD30 (39 %); CD38 (87 %); MUM-1 (91 %); CD138 (79 %); EBER (91 %); and LMP-1 (18 %). There was a marked increase in patients in 2011-12, and the cases found in that period appeared to be more aggressive, showing a higher rate of advanced-stage PBL. Fourteen cases were treated with CHOP, while the others were treated with more intensive regimens, including bortezomib and hematopoietic stem cell transplantation. The overall median survival time was 15 months. A CD4 count of >100/µL at diagnosis and attaining complete remission in the first-line chemotherapy were associated with better outcomes (P = 0.027 and 0.0016, respectively). Host immune status and chemosensitivity are associated with improved prognosis in PBL.
Assuntos
HIV/isolamento & purificação , Linfoma Relacionado a AIDS/terapia , Linfoma Relacionado a AIDS/virologia , Linfoma Plasmablástico/terapia , Linfoma Plasmablástico/virologia , Adulto , Antirretrovirais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Linfócito CD4 , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por Vírus Epstein-Barr/complicações , Feminino , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4/isolamento & purificação , Humanos , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/patologia , Masculino , Pessoa de Meia-Idade , Linfoma Plasmablástico/diagnóstico , Linfoma Plasmablástico/patologia , Prednisona/uso terapêutico , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto JovemRESUMO
Autologous hematopoietic cell transplant (AHCT) for HIV-infected patients is largely limited to centers with HIV-specific expertise. The Blood and Marrow Transplant Clinical Trials Network 0803/AIDS Malignancy Consortium 071 trial is a multicenter phase 2 study of AHCT for patients with HIV-related lymphoma (HRL). Eligible patients had chemotherapy-sensitive relapsed/persistent HRL, were >15 years of age, and had treatable HIV infection. Patients were prepared using carmustine, etoposide, cytarabine, and melphalan and received consistent management of peritransplant antiretroviral treatment. The primary endpoint was 1-year overall survival. Forty-three patients were enrolled; 40 underwent AHCT. Pretransplant HIV viral load was undetectable (<50 copies/mL) in 32 patients (80%); the median CD4 count was 249/µL (range, 39-797). At a median follow-up of 24.8 months, 1-year and 2-year overall survival probabilities were 87.3% (95% confidence interval [CI], 72.1-94.5) and 82% (95% CI, 65.9-91), respectively. The probability of 2-year progression-free survival was 79.8% (95% CI, 63.7-89.4). One-year transplant-related mortality was 5.2%. Median time to neutrophil and platelet recovery was 11 days and 18 days, respectively. Nine patients experienced a total of 13 unexpected grade 3-5 adverse events posttransplant (10 grade 3 and 3 grade 4 events). Twenty-two patients had at least 1 infectious episode posttransplant. At 1 year post-AHCT, median CD4(+) T-cell count was 280.3 (range, 28.8-1148.0); 82.6% had an undetectable HIV viral load. Trial patients were compared with 151 matched Center for International Bone Marrow Transplant Research controls. Outcomes between HIV-infected patients and controls were not statistically significantly different. HRL patients should be considered candidates for AHCT if they meet standard transplant criteria. The trial was registered at www.clinicaltrials.gov as #NCT01141712.
Assuntos
Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Linfoma Relacionado a AIDS/terapia , Adulto , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/mortalidade , Contagem de Linfócito CD4 , Bases de Dados como Assunto , Demografia , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma Relacionado a AIDS/imunologia , Linfoma Relacionado a AIDS/mortalidade , Masculino , Pessoa de Meia-Idade , Transplante Autólogo/efeitos adversos , Resultado do Tratamento , Carga Viral/imunologia , Adulto JovemRESUMO
Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12,135 copies/mL) and 18 patients (median 417 copies/10(6) PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT.
Assuntos
Gammaherpesvirinae/metabolismo , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/terapia , Infecções Tumorais por Vírus/metabolismo , Carga Viral , Adulto , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores/metabolismo , Morte , Feminino , HIV-1/metabolismo , Humanos , Linfoma Relacionado a AIDS/metabolismo , Linfoma Relacionado a AIDS/virologia , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/métodos , Prognóstico , Estudos Retrospectivos , Transplante Autólogo/métodosRESUMO
BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.