RESUMO
Chimeric antigen receptor (CAR) T cells directed against the B-cell marker CD19 are currently changing the landscape for treatment of patients with refractory and/or relapsed B-cell malignancies. Due to the nature of CAR T cells as living drugs, they display a unique toxicity profile. As CAR T-cell therapy is extending towards other diseases and being more broadly employed in hematology and oncology, optimal management strategies of side-effects associated with CAR T-cell therapy are of high relevance. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias constitute challenges in the treatment of patients with CAR T cells. This review summarizes the current understanding of CAR T-cell toxicity and its management.
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Síndromes Neurotóxicas , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Imunoterapia Adotiva , Recidiva Local de Neoplasia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genéticaRESUMO
BACKGROUND: High-dose chemotherapy (HDC) with hematopoietic progenitor cell transplantation is a standard option for relapsed/refractory testicular germ-cell tumor (GCT), but only few data have been reported in female patients with GCT. We conducted a retrospective analysis of female patients with GCT treated with HDC and registered with the European Society for Blood and Marrow Transplantation. PATIENTS AND METHODS: Between 1985 and 2013, 60 registered female patients with GCT, median age 27 years (range 15-48), were treated with salvage HDC. Forty patients (67%) had primary ovarian GCT, 8 (13%) mediastinal, 7 (12%) retroperitoneal and 5 (8%) other primary sites/unknown. Twenty-two patients (37%) received HDC as second-line therapy, 29 (48%) as third-line, and 9 (15%) as fourth- to sixth-line. Nine of 60 patients (15%) received HDC as late-intensification with no evidence of metastasis before HDC. The conditioning HDC regimens comprised carboplatin in 51 of 60 cases (85%), and consisted of a single HDC cycle in 31 cases (52%), a multi-cycle HDC regimen in 29 (48%). RESULTS: Nine cases who underwent late intensification HDC were not evaluable for response. Of the other 51 assessable patients, 17 (33%) achieved a complete response (CR), 8 (16%) a marker-negative partial remission (PRm-), 5 (10%) a marker-positive partial remission, 5 (10%) stable disease, and 13 (25%) progressive disease. There were 3 toxic deaths (6%). With an overall median follow-up of 14 months (range 1-219), 7 of 9 (78%) patients with late intensification and 18 of the 25 patients (72%) achieving a CR/PRm- following HDC were free of relapse/progression. In total, 25 of 60 patients (42%) were progression-free following HDC at a median follow-up of 87 months (range 3-219 months). CONCLUSIONS: Salvage HDC based on carboplatin represents a therapeutic option for female patients with relapsed/refractory GCT.
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Antineoplásicos/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Antineoplásicos/administração & dosagem , Transplante de Medula Óssea , Relação Dose-Resposta a Droga , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante , Adulto JovemRESUMO
BACKGROUND: To evaluate long-term outcome of myeloablative allogeneic stem cell transplantation (allo-SCT) (MAC) versus reduced-intensity allo-SCT (RIC) in patients with relapsed/refractory Hodgkin's lymphoma (HL) in recent years. PATIENTS AND METHODS: A total of 312 patients (63 MAC and 249 RIC) with relapsed/refractory HL who received allo-SCT between 2006 and 2010 and were reported to the EBMT Database were included in the study. RESULTS: With a median follow-up for alive patients of 56 (26-73) months, there were no significant differences in non-relapse mortality (NRM) between MAC and RIC. Relapse rate (RR) was somewhat lower in the MAC group (41% versus 52% at 24 months, P = 0.16). This lower RR translated into a marginal improvement in event-free survival (EFS) for the MAC group (48% versus 36% at 24 months, P = 0.09) with no significant differences in overall survival (73% for MAC and 62% for RIC at 24 months, P = 0.13). Multivariate analysis after adjusting for disease status at the time of allo-SCT showed that the use of MAC was of borderline statistical significance for predicting a lower RR and EFS [HR 0.7, 95% CI (0.5-1.0), P = 0.1] and [HR 0.7, 95% CI (0.5-1.0), P = 0.07], respectively, after allo-SCT. CONCLUSIONS: With modern transplant practices, the NRM associated with MAC for HL has strongly decreased, resulting into non-significant improvement of EFS because of a somewhat better disease control compared with RIC transplants. The intensity of conditioning regimens should be considered when designing individual allo-SCT strategies or clinical trials in patients with relapsed/refractory HL.
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Doença Enxerto-Hospedeiro/epidemiologia , Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Transplante de Células-Tronco/métodos , Transplante Homólogo/métodos , Adulto , Idoso , Medula Óssea , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Doença de Hodgkin/patologia , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Condicionamento Pré-Transplante , Transplante Homólogo/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Patients with follicular lymphoma (FL) relapsing after an autologous transplant (autoSCT) may be treated with a variety of therapies, including a reduced intensity allogeneic transplant (RICalloSCT). We conducted a retrospective analysis of a large cohort of patients undergoing RICalloSCT for FL in this setting. PATIENTS AND METHODS: A total of 183 patients, median age 45 years (range 21-69), had undergone an autoSCT at a median of 30 months before the RICalloSCT. Before the RICalloSCT, they had received a median of four lines (range 3-10) of therapy and 81% of patients had chemosensitive disease and 16% had chemoresistant disease. Grafts were donated from sibling (47%) or unrelated donors (53%). RESULTS: With a median follow-up of 59 months, the non-relapse mortality (NRM) was 27% at 2 years. The median remission duration post-autoSCT and RICalloSCT was 14 and 43 months, respectively. The 5-year relapse/progression rate, progression-free survival and overall survival were 16%, 48% and 51%, respectively, and were associated with age and disease status at RICalloSCT. CONCLUSION: These data suggest that an RICalloSCT is an effective salvage strategy in patients with FL recurring after a prior autoSCT and might overcome the poor prognostic impact of early relapse after autoSCT.
RESUMO
We conducted a questionnaire survey of the 565 European Society for Blood and Marrow Transplantation centers to analyze the outcome of allogeneic hematopoietic stem cell transplantation (alloSCT) in recipients of solid organ transplantation (SOT). We investigated 28 patients with malignant (N = 22) or nonmalignant diseases (N = 6), who underwent 31 alloSCT procedures: 12 after kidney, 13 after liver and 3 after heart transplantation. The incidence of solid organ graft failure at 60 months after first alloSCT was 33% (95% confidence interval [CI], 16-51%) for all patients, 15% (95% CI, 2-40%) for liver recipients and 50% (95% CI, 19-75%) for kidney recipients (p = 0.06). The relapse rate after alloSCT (22%) was low following transplantation for malignant disorders, despite advanced stages of malignancy. Overall survival at 60 months after first alloSCT was 40% (95% CI, 19-60%) for all patients, 51% (95% CI, 16-86%) for liver recipients and 42% (95% CI, 14-70%) for kidney recipients (p = 0.39). In summary, we show that selected SOT recipients suffering from hematologic disorders may benefit from alloSCT and experience enhanced long-term survival without loss of organ function.
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Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Transplante Homólogo , Adulto JovemRESUMO
BACKGROUND: In a single-center retrospective donor versus no-donor comparison, we investigated if allogeneic stem cell transplantation (alloSCT) can improve the dismal course of poor-risk chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: All patients with CLL who were referred for evaluation of alloSCT within a 7-year time frame and had a donor search indication according to the EBMT criteria or because of Richter's transformation were included. Patients for whom a matched donor could be found within 3 months (matches) were compared with patients without such a donor (controls). Primary end point was overall survival measured from the 3-month landmark after search initiation. RESULTS: Of 105 patients with donor search, 97 (matches 83; controls 14) were assessable at the 3-month landmark. Matches and controls were comparable for age, gender, time from diagnosis, number of previous regimens, and remission status. Disregarding if alloSCT was actually carried out or not, survival from the 3-month landmark was significantly better in matches versus controls [hazard ratio 0.38, 95% confidence interval (CI) 0.17-0.85; P = 0.014]. The survival benefit of matches remained significant on multivariate analysis. CONCLUSION: This study provides first comparative evidence that alloSCT may have the potential to improve the natural course of poor-risk CLL as defined by the EBMT criteria.
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Leucemia Linfocítica Crônica de Células B/terapia , Transplante de Células-Tronco , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Doadores de Tecidos , Transplante Homólogo , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem-cell transplantation (ASCT) in a recent time period. PATIENTS: Between 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation (TBI)-containing regimen or carmustin, etoposide, cytarabine and melphalan (BEAM), of which 47% were autografted in first remission. RESULTS: After a median observation time of 73 months (interquartile range 30-107), 5- and 10-year non-relapse mortality (NRM) was similar (6% and 10% in both groups). No significant NRM differences became evident after multivariate adjustment for confounders. Secondary malignancies were observed in 9.7% and 7.9% of the patients after TBI and BEAM (P = 0.19), which were treatment-related myelodysplastic syndromes/acute myelogenous leukaemia (t-MDS/AML) in 3.4% and 2.8% (P = 0.57). The median time to t-MDS/AML was around 50 months in both groups. Because of a lower relapse incidence, TBI was associated with better event-free survival reaching statistical significance in the patients transplanted in first remission but not in those transplanted beyond first remission. CONCLUSIONS: In patients with FL who received TBI-based ASCT after 1995 increased NRM and t-MDS/AML risks did not emerge compared with BEAM while disease control was at least equivalent.
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Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/radioterapia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Terapia Combinada , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Folicular/patologia , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Podofilotoxina/administração & dosagem , Podofilotoxina/efeitos adversos , Indução de Remissão , Rituximab , Transplante de Células-Tronco , Transplante Autólogo , Irradiação Corporal Total , Adulto JovemRESUMO
BACKGROUND: Autologous stem-cell transplantation (autoSCT) is considered a standard treatment of non-frail patients with mantle cell lymphoma (MCL), but little is known about outcome of MCL patients relapsing after autoSCT. We therefore sought to analyse the outcome after autoSCT failure and the efficacy of a rescue stem-cell transplantation (SCT) in this setting. PATIENTS AND METHODS: Patients with MCL were eligible if they had relapsed after autoSCT performed between 2000 and 2009. A total of 1054 patients could be identified in the EBMT registry. By contacting the transplant centres, a full dataset could be retrieved for 360 patients. RESULTS: Median overall survival (OS) after relapse of the whole study group was 19 months. A long (>12 months) interval between autoSCT and relapse [P < 0.001, hazard ratio (HR) 0.62], primary refractory disease (P < 0.02, HR 1.92), prior high-dose ARA-C treatment (P = 0.04, HR 1.43), and the year of relapse (P = 0.02, HR 0.92) significantly influenced OS from relapse in multivariate analysis. Eighty patients (22%) received a rescue allogeneic SCT (alloSCT). Relapse incidence, non-relapse mortality, and OS 2 years after alloSCT was 33% [confidence interval (95% CI 21% to 45%)], 30% (95% CI 19% to 42%), and 46% (95% CI 33% to 59%), respectively. Remission duration after autoSCT was the only variable significantly affecting the outcome of salvage alloSCT. In contrast, rescue autoSCT was not associated with long-term disease control. However, individual patients survived long term even without salvage transplantation. CONCLUSIONS: MCL recurrence within 1 year after autoSCT has an extremely dismal outcome, while the prognosis of patients with longer remission durations after autoSCT is significantly better. AlloSCT may offer the possibility of durable survival when performed for patients with a remission duration of more than 12 months after first autoSCT, but the favourable effect of a salvage alloSCT in this setting needs further validation.
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Linfoma de Célula do Manto/mortalidade , Transplante de Células-Tronco , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Terapia de Salvação , Transplante Autólogo , Falha de Tratamento , Resultado do TratamentoRESUMO
OPINION STATEMENT: The treatment of patients with classical Hodgkin's lymphoma relapsing after autologous stem cell transplantation represents a clear unmet need. Overall long-term outcome is not the same in these patients and therapeutic options in this setting are very heterogeneous and include salvage CT and/or RT followed or not by a second stem cell transplantation, palliative care, new drugs, or biological agents. Despite the absence of prospective, randomized, clinical trials, allogeneic stem cell transplantation either from a HLA identical sibling or a matched, unrelated donor represents an attractive option for those young patients with chemosensitive disease after being treated with a salvage protocol. The use of reduced intensity conditioning regimens has been able to drastically decrease nonrelapse mortality, although relapse rate remains a significant issue in this setting. More intense conditioning protocols could eventually decrease the relapse rate after the allogeneic procedure and, as indicated by a recent retrospective analysis of the Lymphoma Working Party of the European Group for Blood and Marrow Transplantation, nonrelapse mortality does not represent a major problem nowadays for patients with multiply relapsed Hodgkin's lymphoma. Brentuximab vedotin is an antibody-drug conjugate that selectively delivers monomethyl auristatin E, an antimicrotubule agent, into CD30-expressing cells. Its use has been approved recently for patients with Hodgkin's lymphoma relapsing after autologous stem cell transplantation. As a single dose, brentuximab vedotin is able to achieve an objective response rate of 75 % with 34 % of the patients achieving a complete remission. Its widespread use will most certainly change the treatment paradigm of this subgroup of patients, either avoiding the allogeneic procedure in some patients or by increasing the group of potential candidates to an allogeneic transplant being used as a "bridge to allo." Additional information on long-term outcome of patients being treated with this drug or the development of prospective clinical trials in this setting will most probably give some light to this question we have nowadays.
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Doença de Hodgkin/terapia , Transplante de Células-Tronco/métodos , Transplante Homólogo/métodos , Adulto , Fatores Etários , Brentuximab Vedotin , Efeito Enxerto vs Tumor , Antígenos HLA/química , Humanos , Imunoconjugados/administração & dosagem , Microtúbulos/química , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Recidiva , Indução de Remissão , Fatores de Risco , Doadores de Tecidos , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
To complete the existing treatment guidelines for all tumor types, ESMO organizes consensus conferences to better clarify open issues in each disease. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, immediately after the end of the 11th International Conference on Malignant Lymphoma. The consensus conference convened â¼45 experts from all around Europe and selected six lymphoma entities to be addressed; for each of them three to five open questions were to be discussed by the experts. For each question, a recommendation should be given by the panel, supported by the strength of the recommendation based on the level of evidence. This consensus report focuses on the three most common lymphoproliferative malignancies: diffuse large B-cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia. A second report will concentrate on mantle cell lymphoma, marginal zone lymphoma and T-cell lymphomas.
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Leucemia Linfocítica Crônica de Células B/terapia , Linfoma Folicular/radioterapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Gerenciamento Clínico , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/patologia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Guias de Prática Clínica como Assunto , Transplante de Células-TroncoRESUMO
BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed Hodgkin's lymphoma (HL). However, there is currently little information on the predictors of outcome for patients whose disease recurs after ASCT. METHODS: Five hundred and eleven adult patients with relapsed HL after ASCT from EBMT-GITMO databases were reviewed. RESULTS: Treatments administered following ASCT failure included conventional chemotherapy and/or radiotherapy in 294 (64%) patients, second ASCT in 35 (8%), and alloSCT in 133 (29%). After a median follow-up of 49 months, overall survival (OS) was 32% at 5 years. Independent risk factors for OS were early relapse (<6 months) after ASCT, stage IV, bulky disease, poor performance status (PS), and age ≥50 years at relapse. For patients with no risk factors OS at 5 years was 62% compared with 37% and 12% for those having 1 and ≥2 factors, respectively. This score was also predictive for outcome in each group of rescue treatment after ASCT failure. CONCLUSION(S): Early relapse, stage IV, bulky disease, poor PS, and age ≥50 years at ASCT failure are relevant factors for outcome that may help to understand the results of different therapeutic approaches.
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Doença de Hodgkin/mortalidade , Doença de Hodgkin/cirurgia , Recidiva Local de Neoplasia/mortalidade , Transplante de Células-Tronco , Adolescente , Adulto , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Sobrevida , Transplante Autólogo , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: Limited experience is available on the feasibility and efficacy of autologous stem-cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) beyond 65 years. DESIGN AND METHODS: We analysed 712 patients with MCL treated with ASCT from 2000 to 2007 and reported to the European Group for Blood and Marrow Transplantation registry. Patients>65 years were compared with patients<65 years for the end points non-relapse mortality (NRM), relapse incidence, progression-free survival (PFS), and overall survival (OS). RESULTS: Seventy-nine patients were ≥65 years old. Median time from diagnosis to ASCT was longer in the elderly patients (11 versus 9 months, P=0.005); they had more commonly received at least two treatment lines (62.0% versus 47.9%, P=0.02) and were less commonly in first complete remission at ASCT (35.4% versus 51.2%, P=0.002). Median follow-up after ASCT was 19 and 25 months, respectively. NRM was comparable at 3 months (3.8% versus 2.5%) and at 5 years (5.6% versus 5.0%). There were no differences in relapse rate (66% versus 55% at 5 years), PFS (29% versus 40%) and OS (61% versus 67%) between both populations of patients. CONCLUSION: ASCT beyond 65 years of age is feasible in selected patients with MCL and results in similar disease control and survival as in younger patients.
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Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/cirurgia , Transplante de Células-Tronco/mortalidade , Adulto , Distribuição por Idade , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Transplante AutólogoRESUMO
BACKGROUND: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. PATIENTS AND METHODS: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. RESULTS: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). CONCLUSIONS: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols.
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Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Doença Enxerto-Hospedeiro/terapia , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10-13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40-54) with only 4 patients relapsing after 7.5 years. RM continues to significantly improve 10-year PFS after ASCT in comparison with NM [P = 0.002; HR 0.548 (95% CI 0.38-0.80)]. Ten-year non-relapse mortality (NRM) was not significantly different between treatment groups (7% overall). 10-year overall survival (OS) after ASCT was 75% (69-81) for the whole series, with no significant differences according to treatment sub-groups. 10-year OS for patients who progressed within 24 months (POD24T) was 60%, in comparison with 85% for patients without progression. Thus the benefit of rituximab maintenance after ASCT on relapse prevention is sustained at 12 years, suggesting that RM adds to ASCT-mediated disease eradication and may enhance the curative potential of ASCT.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Folicular , Protocolos de Quimioterapia Combinada Antineoplásica , Autoenxertos , Terapia Combinada , Seguimentos , Humanos , Linfoma Folicular/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos Prospectivos , Estudos Retrospectivos , Rituximab/uso terapêutico , Transplante AutólogoRESUMO
Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p < 0.001, OR 3.69, 95% CI 2.09-6.54, p < 0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.
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Doenças Cardiovasculares , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndrome Metabólica , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Síndrome Metabólica/etiologia , Transplante Homólogo/efeitos adversosRESUMO
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment option in advanced-stage mycosis fungoides (MF) and Sézary syndrome (SS). This study presents an updated analysis of the initial experience of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT) describing the outcomes after allo-HSCT for MF and SS, with special emphasis on the impact of the use of unrelated donors (URD). METHODS AND PATIENTS: Eligible for this study were patients with advanced-stage MF or SS who underwent a first allo-HSCT from matched HLA-identical related or URD between January/1997 and December/2011. Sixty patients have been previously reported. RESULTS: 113 patients were included [77 MF (68%)]; 61 (54%) were in complete or partial remission, 86 (76%) received reduced-intensity protocols and 44 (39%) an URD allo-HSCT. With a median follow up for surviving patients of 73 months, allo-HSCT resulted in an estimated overall survival (OS) of 38% at 5 years, and a progression-free survival (PFS) of 26% at 5 years. Multivariate analysis demonstrated that advanced-phase disease (complete remission/partial remission >3, primary refractory or relapse/progression in patients that had received 3 or more lines of systemic treatment prior to transplant or the number of treatment lines was not known), a short interval between diagnosis and transplant (<18 months) were independent adverse prognostic factors for PFS; advanced-phase disease and the use of URDs were independent adverse prognostic factors for OS. CONCLUSIONS: This extended series supports that allo-HSCT is able to effectively rescue over one third of the population of patients with advanced-stage MF/SS. High relapse rate is still the major cause of failure and needs to be improved with better strategies before and after transplant. The negative impact of URD is a matter of concern and needs to be further elucidated in future studies.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Medula Óssea , Humanos , Micose Fungoide/terapia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Síndrome de Sézary/terapia , Transplante HomólogoRESUMO
Information regarding the curative role of allogeneic stem cell transplantation (allo-HCT) in systemic anaplastic large cell lymphoma (sALCL) is scarce. We analyzed the results of allo-HCT in patients with relapsed/refractory sALCL with special emphasis on the role of brentuximab vedotin (BV) as a bridge to allo-HCT. Forty-four patients (24 females, median age 38 years) with sALCL were included. Twenty-three patients (52%) received BV before allo-HCT; BV-treated patients were more heavily pretreated (≥3 lines of therapy in 74% vs. 38%, p = 0.04). Twenty-three patients (52%) were in complete remission (CR) at allo-HCT. Three-year nonrelapse mortality and incidence of relapse (IR) after allo-HCT were 7% and 40%, respectively. With a median follow-up of 39 (12-69) months for survivors, 3-year progression-free survival (PFS) and overall survival were 53% and 74%, respectively. Univariate analysis showed that heavily pretreated patients and those not in CR had a higher IR and a lower PFS. The use of BV before transplant did not impact on any of the outcomes. Allo-HCT is a curative therapeutic strategy in a significant proportion of patients with relapsed/refractory sALCL; BV does not seem to modify transplant-related outcomes but might be able to render more patients candidates for this curative treatment.