RESUMO
Loncastuximab tesirine-lpyl (ADC Therapeutics), an anti-CD19 antibody-drug conjugate, was recently approved for the treatment of relapsed, refractory diffuse large B-cell lymphoma on the basis of the results of a phase II clinical trial, LOTIS-2. Preclinical data demonstrated the selectivity and efficacy of the drug through in vitro and in vivo models. A phase I clinical trial included relapsed, refractory B-cell non-Hodgkin lymphoma (NHL) and demonstrated a tolerable safety profile, with major adverse effects being neutropenia, thrombocytopenia and elevated gamma-glutamyl transferase (GGT). A dose of 150 µg/kg intravenously every 3 weeks for two cycles followed by 75 µg/kg every 3 weeks was chosen for further testing. The phase II trial, LOTIS-2, recruited relapsed, refractory diffuse large B-cell lymphoma patients and demonstrated no new safety concerns. Overall response rate was 48.3% (24.1% CR), and OS was 9.9 months. Currently, several ongoing clinical trials are evaluating the safety and efficacy of loncastuximab tesirine in a variety of NHL subtypes.
Assuntos
Linfoma Difuso de Grandes Células B , Recidiva Local de Neoplasia , Anticorpos Monoclonais Humanizados , Benzodiazepinas , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Resultado do TratamentoRESUMO
The development of hematopoietic stem cell transplantation (HSCT) programs can face significant challenges in most developing countries because such endeavors must compete with other government health care priorities, including the delivery of basic services. While this is may be a limiting factor, these countries should prioritize development of the needed expertise to offer state of the art treatments including transplantation, by providing financial, technological, legal, ethical and other needed support. This would prove beneficial in providing successful programs customized to the needs of their population, and potentially provide long-term cost-savings by circumventing the need for their citizens to seek care abroad. Costs of establishing HSCT program and the costs of the HSCT procedure itself can be substantial barriers in developing countries. Additionally, socioeconomic factors intrinsic to specific countries can influence access to HSCT, patient eligibility for HSCT and timely utilization of HSCT center capabilities. This report describes recommendations from the Worldwide Network for Blood and Marrow Transplantation (WBMT) for establishing HSCT programs with a specific focus on developing countries, and identifies challenges and opportunities for providing this specialized procedure in the resource constrained setting.
Assuntos
Transplante de Medula Óssea/métodos , Países em Desenvolvimento/estatística & dados numéricos , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Humanos , Fatores SocioeconômicosAssuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Transplante Autólogo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Feminino , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Estados Unidos/epidemiologiaRESUMO
The advent of novel immunotherapy and tyrosine kinase inhibitors has ushered a new era in the treatment of Hodgkin and non-Hodgkin lymphomas. Allogeneic hematopoietic cell transplantation remains, however, a vital component in the management and potential cure of lymphomas, especially in the relapsed setting. Considering the biological and clinical heterogeneity of various subtypes of lymphomas, the optimal intensity of conditioning regimens remains controversial. Reduced intensity conditioning regimens have broadened applicability of the procedure to older and frail patients. Observational studies suggest that although reduced intensity allografting is associated with higher risk of relapse, overall survival is comparable and in some cases even better, than observed with myeloablative regimens. Here, we review the available published data pertaining to allogeneic hematopoietic cell transplantation using reduced intensity or myeloablative conditioning for various lymphoma histologies. Owing to the lack of randomized prospective trials, recommendations are mainly based on registry and single-institution studies. Special emphasis must be given to implementing strategies to prevent relapse when using reduced intensity regimens. Identifying particular patients who may benefit from myeloablative regimens in lymphomas remains to be better defined.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Agonistas Mieloablativos/administração & dosagem , Humanos , Condicionamento Pré-Transplante/métodos , Transplante HomólogoRESUMO
Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.
Assuntos
Doenças Cardiovasculares , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndrome Metabólica , Aloenxertos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Humanos , Síndrome Metabólica/etiologia , Síndrome Metabólica/prevenção & controle , Guias de Prática Clínica como AssuntoAssuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/terapia , Tiotepa/administração & dosagem , Adulto , Idoso , Autoenxertos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tiotepa/efeitos adversos , Fatores de TempoAssuntos
Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Viroses/etiologia , Adulto , Idoso , Proliferação de Células , Ciclofosfamida/administração & dosagem , DNA Viral/análise , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Células-Tronco Hematopoéticas/citologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Linfócitos T/citologia , Resultado do Tratamento , Viroses/prevenção & controleRESUMO
Grade 3 follicular lymphoma (FL) has aggressive clinical behavior. To evaluate the optimal first transplantation approach in relapsed/refractory grade 3 FL patients, we compared the long-term outcomes after allogeneic (allo-) vs autologous hematopoietic cell transplantation (auto-HCT) in the rituximab era. A total of 197 patients undergoing first reduced-intensity conditioning (RIC) allo-HCT or first auto-HCT during 2000-2012 were included. Rituximab-naive patients were excluded. Allo-HCT recipients were younger, more heavily pretreated and had a longer interval between diagnosis and HCT. The 5-year probabilities of non-relapse mortality (NRM), relapse/progression, PFS and overall survival (OS) for auto-HCT vs allo-HCT groups were 4% vs 27% (P<0.001), 61% vs 20% (P<0.001), 36% vs 51% (P=0.07) and 59% vs 54% (P=0.7), respectively. On multivariate analysis, auto-HCT was associated with reduced risk of NRM (relative risk (RR)=0.20; P=0.001). Within the first 11 months post HCT, auto- and allo-HCT had similar risks of relapse/progression and PFS. Beyond 11 months, auto-HCT was associated with higher risk of relapse/progression (RR=21.3; P=0.003) and inferior PFS (RR=3.2; P=0.005). In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.42; P=0.005), but in long-time survivors (beyond 24 months) it was associated with inferior OS (RR=3.6; P=0.04). RIC allo-HCT as the first transplant approach can provide improved PFS and OS, in long-term survivors.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Folicular/mortalidade , Linfoma Folicular/terapia , Adulto , Idoso , Aloenxertos , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Fatores de TempoAssuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Linfoma de Célula do Manto , Úlcera Cutânea , Autoenxertos , Infecções por Vírus Epstein-Barr/etiologia , Infecções por Vírus Epstein-Barr/patologia , Humanos , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Úlcera Cutânea/etiologia , Úlcera Cutânea/patologiaRESUMO
Autologous hematopoietic cell transplantation (AutoHCT) is a potentially curative treatment modality for relapsed/refractory Hodgkin lymphoma (HL). However, no large studies have evaluated pretransplant factors predictive of outcomes of AutoHCT in children, adolescents and young adults (CAYA, age <30 years). In a retrospective study, we analyzed 606 CAYA patients (median age 23 years) with relapsed/refractory HL who underwent AutoHCT between 1995 and 2010. The probabilities of PFS at 1, 5 and 10 years were 66% (95% confidence interval (CI): 62-70), 52% (95% CI: 48-57) and 47% (95% CI: 42-51), respectively. Multivariate analysis for PFS demonstrated that at the time of AutoHCT patients with Karnofsky/Lansky score ⩾90, no extranodal involvement and chemosensitive disease had significantly improved PFS. Patients with time from diagnosis to first relapse of <1 year had a significantly inferior PFS. A prognostic model for PFS was developed that stratified patients into low-, intermediate- and high-risk groups, predicting for 5-year PFS probabilities of 72% (95% CI: 64-80), 53% (95% CI: 47-59) and 23% (95% CI: 9-36), respectively. This large study identifies a group of CAYA patients with relapsed/refractory HL who are at high risk of progression after AutoHCT. Such patients should be targeted for novel therapeutic and/or maintenance approaches post-AutoHCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Modelos Teóricos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Causas de Morte , Criança , Pré-Escolar , Terapia Combinada , Progressão da Doença , Intervalo Livre de Doença , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Doença de Hodgkin/radioterapia , Humanos , Masculino , Segunda Neoplasia Primária/epidemiologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Terapia de Salvação , Transplante Autólogo , Adulto JovemRESUMO
In patients with multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (auto-HCT), peripheral blood progenitor cells may be collected following mobilization with growth factor alone (GF) or cytotoxic chemotherapy plus GF (CC+GF). It is uncertain whether the method of mobilization affects post-transplant outcomes. We compared these mobilization strategies in a retrospective analysis of 968 patients with MM from the Center for International Blood and Marrow Transplant Research database who received an auto-HCT in the US and Canada between 2007 and 2012. The kinetics of neutrophil engraftment (⩾0.5 × 10(9)/L) was similar between groups (13 vs 13 days, P=0.69) while platelet engraftment (⩾20 × 10(9)/L) was slightly faster with CC+GF (19 vs 18 days, P=0.006). Adjusted 3-year PFS was 43% (95% confidence interval (CI) 38-48) in GF and 40% (95% CI 35-45) in CC+GF, P=0.33. Adjusted 3-year OS was 82% (95% CI 78-86) vs 80% (95% CI 75-84), P=0.43 and adjusted 5-year OS was 62% (95% CI 54-68) vs 60% (95% CI 52-67), P=0.76, for GF and CC+GF, respectively. We conclude that MM patients undergoing auto-HCT have similar outcomes irrespective of the method of mobilization and found no evidence that the addition of chemotherapy to mobilization contributes to disease control.
Assuntos
Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/sangue , Mieloma Múltiplo/terapia , Adolescente , Adulto , Idoso , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Recuperação de Função Fisiológica , Taxa de SobrevidaRESUMO
Disease relapse after autologous hematopoietic transplant (auto-HCT) remains the number one cause of post-transplant therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at the prevention of post-auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. Although high dose therapy (HDT) provides durable responses in chemosensitive relapsed diffuse large B-cell lymphoma (DLBCL), a sizable subset experiences disease relapse. Unfortunately, the addition of rituximab as a post-auto-HCT maintenance strategy did not improve survival outcomes. The preliminary results with programmed death -1 (PD-1) Ab as post-auto maintenance in DLBCL is promising but requires randomized validation. In follicular lymphoma, the 5- and 10-year PFS rates are ~60% and 31%, respectively. Although the addition of rituximab improved PFS, there is no survival benefit, to date. Disease relapse after auto-HCT in mantle cell lymphoma (MCL) is not uncommon. Rituximab maintenance in this setting provides a PFS benefit. Given the poor prognosis of post-auto-HCT failures in MCL, maintenance can be considered on a case-by-case basis. In chemosensitive relapsed Hodgkin lymphoma, addition of brentuximab vedotin after auto-HCT improved 2-year PFS (65 vs 45%) and can be considered as an option for maintenance therapy post auto-HCT, in select higher risk patients. Ongoing trials evaluating the efficacy of post-auto-HCT maintenance with novel agents (for example, immunomodulators, proteasome inhibitors, PD-1 inhibitors, Bruton's tyrosine kinase inhibitors and so on) will likely change the practice landscape for lymphoma patients following HDT and auto-HCT.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Imunoterapia , Linfoma/terapia , Quimioterapia de Manutenção , Terapia de Alvo Molecular , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ensaios Clínicos como Assunto , Terapia Combinada , Intervalo Livre de Doença , Previsões , Genes cdc , Inibidores de Histona Desacetilases/administração & dosagem , Humanos , Imunotoxinas/uso terapêutico , Linfoma/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Taxa de Sobrevida , Transplante Autólogo , Resultado do TratamentoRESUMO
The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Neoplasias Meníngeas , Segunda Neoplasia Primária , Sarcoma Mieloide , Neoplasias Cutâneas , Adolescente , Adulto , Idoso , Aloenxertos , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/terapia , Pessoa de Meia-Idade , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/terapia , Sarcoma Mieloide/mortalidade , Sarcoma Mieloide/terapia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapiaRESUMO
Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Programas de Rastreamento , Segunda Neoplasia Primária/diagnóstico , Feminino , Humanos , Masculino , Segunda Neoplasia Primária/epidemiologia , Especificidade de Órgãos , Fatores de RiscoAssuntos
Amiloidose , Fator Estimulador de Colônias de Granulócitos , Mobilização de Células-Tronco Hematopoéticas/economia , Células-Tronco Hematopoéticas , Compostos Heterocíclicos , Amiloidose/economia , Amiloidose/terapia , Benzilaminas , Custos e Análise de Custo , Ciclamos , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/economia , Compostos Heterocíclicos/administração & dosagem , Compostos Heterocíclicos/economia , Humanos , Masculino , Estudos RetrospectivosAssuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndrome Nefrótica/etiologia , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transplantados , Condicionamento Pré-Transplante/efeitos adversos , Transplante HomólogoRESUMO
Hodgkin lymphoma (HL) relapsing after an autologous hematopoietic cell transplant (HCT) poses a therapeutic challenge. In this setting, salvage chemotherapy (for example, gemcitabine-based, ifosfamide-containing and others) or immunotherapy (for example, brentuximab vedotin) is essential as a bridging-cytoreduction strategy to an allogeneic HCT. Myeloablative allogeneic hematopoietic cell transplantation in relapsed HL is associated with high rates of non-relapse mortality. In carefully selected patients with chemosensitive disease, allografting following lower-intensity conditioning regimens can provide durable disease control rates of about 25-35%. Promising early results with haploidentical and umbilical cord transplantation are noteworthy and are expanding this procedure to patients for whom HLA-matched related or unrelated donors are not available. Unfortunately, a significant number of HL patients relapsing after an autologous HCT are not candidates for allografting because of the presence of resistant disease, donor unavailability or comorbidities. Brentuximab vedotin is approved for HL relapsing after a prior autograft. Rituximab and bendamustine are also active in this setting, albeit with short durations of remission. Histone deacetylase inhibitors (for example, panobinostat, mocetinostat), mTOR inhibitors (for example, everolimus) and immunomodulatory agents (lenalidomide) have shown activity in phase II trials, but currently are not approved for this indication. Second autologous HCT are rarely performed but this approach should not be considered standard practice at this time. The need for effective agents for post autograft failures of HL largely remains unmet. Continuous efforts to ensure early referral of such patients for allogeneic HCT or investigational therapies are the key to improving outcomes of this not-so-good lymphoma.