RESUMO
The prognosis of relapsed primary central nervous system lymphoma (PCNSL) remains dismal. CAR T-cells are a major contributor to systemic lymphomas, but their use in PCNSL is limited. From the LOC network database, we retrospectively selected PCNSL who had leukapheresis for CAR-T cells from the third line of treatment, and, as controls, PCNSL treated with any treatment, at least in the third line and considered not eligible for ASCT. Twenty-seven patients (median age: 68, median of three previous lines, including ASCT in 14/27) had leukapheresis, of whom 25 received CAR T-cells (tisa-cel: N = 16, axi-cel: N = 9) between 2020 and 2023. All but one received a bridging therapy. The median follow-up after leukapheresis was 20.8 months. The best response after CAR-T cells was complete response in 16 patients (64%). One-year progression-free survival from leukapheresis was 43% with a plateau afterward. One-year relapse-free survival was 79% for patients in complete or partial response at CAR T-cell infusion. The median overall survival was 21.2 months. Twenty-three patients experienced a cytokine release syndrome and 17/25 patients (68%) a neurotoxicity (five grade ≥3). The efficacy endpoints were significantly better in the CAR T-cell group than in the control group (N = 247) (median PFS: 3 months; median OS: 4.7 months; p < 0.001). This series represents the largest cohort of PCNSL treated with CAR T-cells reported worldwide. CAR T-cells are effective in relapsed PCNSL, with a high rate of long-term remission and a reassuring tolerance profile. The results seem clearly superior to those usually observed in this setting.
Assuntos
Neoplasias do Sistema Nervoso Central , Imunoterapia Adotiva , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Masculino , Feminino , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias do Sistema Nervoso Central/mortalidade , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Leucaférese , Indução de Remissão , Adulto , Idoso de 80 Anos ou mais , Receptores de Antígenos QuiméricosRESUMO
Ibrutinib has revolutionized the management of chronic lymphocytic leukemia and is now being increasingly used. Although considered to be less immunosuppressive than conventional immunochemotherapy, the observation of a few cases of invasive fungal infections in patients treated with ibrutinib prompted us to conduct a retrospective survey. We identified 33 cases of invasive fungal infections in patients receiving ibrutinib alone or in combination. Invasive aspergillosis (IA) was overrepresented (27/33) and was associated with cerebral localizations in 40% of the cases. Remarkably, most cases of invasive fungal infections occurred with a median of 3 months after starting ibrutinib. In 18/33 cases, other conditions that could have contributed to decreased antifungal responses, such as corticosteroids, neutropenia, or combined immunochemotherapy, were present. These observations indicate that ibrutinib may be associated with early-onset invasive fungal infections, in particular IA with frequent cerebral involvement, and that patients on ibrutinib should be closely monitored in particular when other risk factors of fungal infections are present.
Assuntos
Aspergilose/induzido quimicamente , Aspergilose/epidemiologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/epidemiologia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Adenina/análogos & derivados , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/microbiologia , Masculino , Piperidinas , Fatores de TempoAssuntos
Neoplasias do Sistema Nervoso Central/terapia , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B/terapia , Idoso , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/patologia , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Análise de SobrevidaAssuntos
Doenças Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombocitopenia/tratamento farmacológico , Trombopoetina/uso terapêutico , Adulto , Idoso , Feminino , Seguimentos , Doenças Hematológicas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Trombocitopenia/etiologia , Trombocitopenia/patologiaRESUMO
BACKGROUND: Neutrophils are key effectors against the widely distributed mold Aspergillus fumigatus, which is a major threat for immunocompromised patients, including allogeneic hematopoietic stem cell transplant (HSCT) recipients. Yet little is known about neutrophil activity over time after cell transplantation, especially regarding A fumigatus. OBJECTIVE: We aimed at assessing the activity of neutrophils on A fumigatus in allogeneic HSCT recipients at different posttransplantation time points. METHODS: We performed a longitudinal study involving 37 patients undergoing HSCT, drawing blood samples at engraftment and at 2, 6, and 10 months after the HSCT. Posttransplantation neutrophil activity in the recipients was compared with that of the respective donors. Neutrophil/A fumigatus coculture, flow cytometry, and video microscopy were used to assess neutrophil inhibition of fungal growth, cell/fungus interactions, reactive oxygen species production, major surface molecule expression, and neutrophil extracellular trap (NET) formation. RESULTS: The ability of neutrophils to interfere with Aspergillus species hyphal growth was impaired after HSCT. The administration of calcineurin inhibitors appeared to play an important role in this impairment. We also observed that post-HSCT neutrophils produced less NETs, which was correlated with increased fungal growth. Tapering immunosuppression led to the recuperation of inhibition capacity 10 months after HSCT. CONCLUSION: In HSCT recipients neutrophil-driven innate immunity to fungi is altered in the early posttransplantation period (between recovery from neutropenia and up to 6 months). This alteration is at least partly related to administration of calcineurin inhibitors and diminution of NETs production.
Assuntos
Aspergillus fumigatus/crescimento & desenvolvimento , Inibidores de Calcineurina/farmacologia , Transplante de Células-Tronco Hematopoéticas , Neutrófilos/efeitos dos fármacos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adulto JovemRESUMO
Waldenstrom's macroglobulinemia is generally treated with alkylating agents, purine analogs and monoclonal antibodies, alone or in combination. We report the outcomes of 82 patients (median age 61 years) treated with the RFC combination. Twenty-five patients were treatment-naive. RFC was administered every 4 weeks, for a median of five cycles. At treatment discontinuation, the overall response rate was 85.4%. The responses improved after treatment discontinuation in 25 patients, with a median time to best response achievement of 10.8 months, raising the major response rate (PR, VGPR and CR) from 64.6% to 76.8%. With a median follow-up of 47 months, the median progression-free survival time had not been reached (67% PFS at 48 months) and was influenced by age and treatment status before RFC. Likewise, the median time to next therapy had not been reached. Two cases of myelodysplastic syndrome/AML and 3 cases of transformation to aggressive lymphoma occurred. Thirteen patients died. The 3-year overall survival rate was 90%. Long-lasting cytopenias occurred in 19 patients. The RFC combination thus gave a high response rate and durable responses, even in heavily treatment-experienced patients. The high incidence of long-lasting cytopenia might be reduced by giving fewer courses and thereby minimizing myelotoxicity. Am. J. Hematol. 91:782-786, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transformação Celular Neoplásica/induzido quimicamente , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancitopenia/induzido quimicamente , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Macroglobulinemia de Waldenstrom/mortalidade , Macroglobulinemia de Waldenstrom/patologiaRESUMO
Acute GVHD is a potentially severe complication of hematopoietic stem cell transplantation, responsible for morbidity and mortality that can affect the prognosis after transplantation. Within the framework of the 12th workshop of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), diagnostic modalities of acute GVHD are updated. The conventional prevention (depending on donor, conditioning, and stem cell source) and treatment schemes (depending on affected organ and intensity) of aGVHD are clarified, and new therapeutic options are discussed.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Condicionamento Pré-Transplante/efeitos adversos , Transplante de Medula Óssea , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Homólogo/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Sociedades MédicasRESUMO
Autologous and allogeneic hematopoietic stem cell transplantation (HSCT) can lead to early cardiac complications as well as late sequelae. A cardiac evaluation is essential in the pre-transplant assessment given the patient's comorbidities and previous chemotherapy treatments received. Various thresholds of cardiac function are recommended as eligibility criteria. The rise of haplo-identical transplantation with the use of post-transplant high-dose cyclophosphamide (PT-Cy) as a prophylaxis against graft-versus-host disease (GVHD) is accompanied by a resurgence of cardiological concerns. Arrhythmias are also a concern and the list of drugs implicated in this complication is growing. The rare occurrence of cardiac GVHD has been reported, although the entity is not well defined. Finally, although long-term follow-up recommendations exist, they are not accompanied by specific targets for cardiovascular risk factors, the presence of which is nevertheless increased after HSCT. In the framework of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) practice harmonization workshops held in Lille in September 2019, the prophylaxis, the diagnostic approach and the treatments of cardiac complication following HSCT were reviewed after analysis of published studies.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Medula Óssea , Ciclofosfamida , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , ComorbidadeRESUMO
Norovirus (NoV) and Sapovirus (SaV) are potential causative agents of diarrhea after allogeneic HSCT but little is known in this population. We performed a retrospective analysis by RT-PCR of calicivirus (NoV and SaV), Human adenovirus (HAdV), rotavirus (RV), Aichi virus (AiV), enterovirus (EV), human parechovirus (HPeV) and Human bocavirus (HBoV) in the diarrheal stools of patients after allogeneic HSCT. 49/162 patients had positive viral assays: HAdV (17%), EV (7%), NoV (4.3%), RV and HBoV (3.1% each), SaV (1.9%), AiV (1.2%), HPeV (0.6%). Seven patients were positive for NoV and 3 for SaV. Among viruses-positive samples, the frequency of caliciviruses cases was 7% in the 6 months post-HSCT compared to 40% after (p < 0.0001). The median duration of symptom was 0.7 months but 2 cases, occurring more than one year after HSCT, were chronic, undiagnosed and strongly contributed to morbidity. Systematic testing of caliciviruses appears especially useful in late chronic diarrhea.
Assuntos
Gastroenterite , Transplante de Células-Tronco Hematopoéticas , Norovirus , Sapovirus , Humanos , Lactente , Sapovirus/genética , Norovirus/genética , Gastroenterite/diagnóstico , Gastroenterite/epidemiologia , Gastroenterite/etiologia , Estudos Retrospectivos , Diarreia/diagnóstico , Diarreia/etiologia , Diarreia/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosAssuntos
Infecções por Adenoviridae/imunologia , Adenoviridae/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Linfócitos T/imunologia , Adulto , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Given the poor prognosis of relapsed/refractory myeloid malignancies, the concept of sequential conditioning before allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven to be an effective approach. We sought to evaluate a sequential scheme combining fludarabine, amsacrine, and cytarabine (FLAMSA) for cytoreduction, followed by reduced-intensity conditioning with busulfan and melphalan (FLAMSA-BuMel), which was designed to be suitable for both HLA-matched and haploidentical HSCT. This single-center retrospective study included 36 adult patients with high-risk myeloid malignancies who underwent allo-HSCT from HLA-matched (n = 19) or haploidentical (n = 17) donors. Along with the standard prophylaxis for graft-versus-host disease (GVHD), patients with a haploidentical donor received post-transplantation high-dose cyclophosphamide. A post-transplantation consolidation treatment with low-dose 5-azacytidine and prophylactic donor lymphocyte infusions was provided whenever possible. Thirty patients (83%) achieved complete remission on day +30. With a median follow-up of 30.0 months, the 2-year overall survival was 89% in the HLA-matched group versus 34% in the haploidentical group (P = .0018). The 2-year disease-free survival in these 2 groups was 68% and 34%, respectively (P = .013). At 2 years, the probability of relapse was 32% and 20%, respectively, and nonrelapse mortality was 0% and 58%, respectively (P = .0003). The leading cause of death was relapse in the HLA-matched group (3 of 19) and hemorrhagic events (5 of 17) in the haploidentical group, favored by significantly delayed platelet reconstitution and a severe GVHD context. These data confirm the feasibility of FLAMSA-BuMel as a sequential conditioning in allo-HSCT for high-risk myeloid malignancies. The use of bone marrow as the preferred graft source might reduce the incidence of acute GVHD and nonrelapse mortality in the haploidentical transplantation setting.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Bussulfano , Humanos , Leucemia Mieloide Aguda/terapia , Melfalan , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organizes annual workshops in the attempt to harmonize clinical practices among different francophone transplantation centers. Here we report our recommendations regarding detection of the multidrug-resistant bacteria in hematology.
Assuntos
Farmacorresistência Bacteriana Múltipla , Transplante de Células-Tronco Hematopoéticas , Aloenxertos , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/transmissão , Portador Sadio/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/prevenção & controle , Suscetibilidade a Doenças , Neoplasias Hematológicas/microbiologia , Neoplasias Hematológicas/terapia , Humanos , Risco , TransplantadosRESUMO
The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organizes annual workshops in the attempt to harmonize clinical practices among different francophone transplantation centers. Here, we report our recommendations regarding the prophylaxis of cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV) and hepatitis B virus infection after allogeneic hematopoietic cell transplantation in adult patients.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatite B/prevenção & controle , Herpes Simples/prevenção & controle , Herpes Zoster/prevenção & controle , Condicionamento Pré-Transplante/efeitos adversos , Acetatos/administração & dosagem , Acetatos/uso terapêutico , Adulto , Aloenxertos , Antivirais/administração & dosagem , Infecções por Citomegalovirus/tratamento farmacológico , Hepatite B/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Herpes Zoster/tratamento farmacológico , Humanos , Quinazolinas/administração & dosagem , Quinazolinas/uso terapêuticoRESUMO
INTRODUCTION: Allogeneic stem cell transplantation is currently the only curative therapy for hematological disorders. This treatment can lead to complications, of which ophtalmological involvement. METHODS: We reviewed the literature and established accessible and convenient recommendations for hematologists and ophthalmologists. RESULTS: Ophtalmological follow-up should be done in every patient having had an allogeneic transplantation, by the hematologist questioning and by the ophthalmologist physical exam. Complications due to graft-versus-host disease (GVHD) or not due to GVHD are cited, as well as therapeutic options. DISCUSSION: Screening and treatment of ophthalmologic complications in allogeneic stem cells transplantation recipients requires a close collaboration between hematologists and ophthalmologists. The management of these patients by caregivers trained in these questions is encouraged.
Assuntos
Oftalmopatias/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Oftalmopatias/diagnóstico , Oftalmopatias/terapia , Doença Enxerto-Hospedeiro/complicações , Doenças Hematológicas/terapia , Hematologia , Humanos , Oftalmologistas , Sociedades Médicas , Transplante Homólogo/efeitos adversosRESUMO
Stomatological complications of allogeneic hematopoietic stem cell transplantation (HSCT) are frequent and very uncomfortable for patients. The primary complication is the graft versus host disease reaction. Other side effects of the procedure include infections, taste disorders and carcinogenic risks. Various local treatments are used but remain imperfect. Within the framework of the 10th workshop of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held in Lille in September 2019, diagnostic approaches and treatments of tongue and oral complications following allogeneic HSCT were reviewed according to the analysis of published studies.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças da Boca/etiologia , Doença Aguda , Candidíase Bucal/diagnóstico , Candidíase Bucal/etiologia , Candidíase Bucal/terapia , Carcinoma de Células Escamosas/etiologia , Doença Crônica , Cárie Dentária/etiologia , Cárie Dentária/prevenção & controle , Gota/etiologia , Doença Enxerto-Hospedeiro/complicações , Humanos , Doenças da Boca/diagnóstico , Doenças da Boca/terapia , Neoplasias Bucais/etiologia , Doenças Periodontais/etiologia , Sociedades Médicas , Doenças da Língua/diagnóstico , Doenças da Língua/etiologia , Doenças da Língua/terapia , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversosAssuntos
Aciclovir , Antivirais , Farmacorresistência Viral , Transplante de Células-Tronco Hematopoéticas , Herpes Simples , Humanos , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Simples/tratamento farmacológico , Herpes Simples/virologia , Simplexvirus/efeitos dos fármacos , Transplantados , Transplante Homólogo/efeitos adversos , Resultado do TratamentoRESUMO
In September 2016 in Lille, France, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 7th Allogeneic Stem Cell Transplantation Clinical Practices Harmonization Workshop Series. Our work group focused on chemotherapy drug dose adaptation for hematopoietic stem cell transplantation patients presenting a comorbidity. The purpose of this workshop was to provide recommendations on chemotherapy drug dose adaptation for patient populations receiving hematopoietic stem cell transplantation who also had the following comorbidities: obesity, chronic kidney disease and hepatopathy.