RESUMO
We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Adulto , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
The effects of graft or donor characteristics in haploidentical hematopoietic cell transplantation (HCT) using post-transplant cyclophosphamide (PT-Cy) are largely unknown. In this multicenter retrospective study we analyzed the correlations between graft cell composition (CD34+, CD3+) and donor features on transplant outcomes in 234 patients who underwent HCT between 2010 and 2016. On multivariate analysis, the use of peripheral blood stem cells (PBSC) was associated with an increased incidence of grade 2-4 acute GVHD [HR 1.94, 95% confidence Interval (CI) = 1.01-3.98, p = 0.05]. An elevated CD3+ graft content was associated with an increased incidence of all-grade chronic GVHD [HR 1.36 (95% CI = 1.06-1.74), p = 0.01]. This effect was confirmed only for the PBSC graft group. A higher CD34+ graft content had a protective role on non-relapse mortality [HR 0.78 (95% CI = 0.62-0.96), p = 0.02] but this was confirmed only for the bone marrow (BM)-derived graft cohort. Donor characteristics did not influence any outcomes. GVHD prophylaxis should be modulated accordingly to CD3+ graft content, especially when a PBSC graft is used. These results need further validation in prospective trials.
Assuntos
Complexo CD3/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Haploidêntico/efeitos adversos , Transplante Homólogo/efeitos adversos , Adulto , Idoso , Doença Crônica , Estudos de Coortes , Ciclofosfamida , Feminino , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Haploidêntico/métodos , Transplante Homólogo/métodos , Adulto JovemRESUMO
This corrects the article DOI: 10.1038/bmt.2012.225.
RESUMO
We investigated the use of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of advanced Hodgkin lymphoma (HL). Sixty-two consecutive HL patients underwent haplo-HSCT. Unmanipulated stem cells and post-transplant cyclophosphamide were given to all patients as GVHD prophylaxis. At 100 days, the cumulative incidence of grades 2-3 and grades 3-4 acute GVHD was 23% and 4%, respectively. The chronic GVHD (cGVHD) cumulative incidence was 16%, with one patient experiencing severe cGVHD. The 3-year OS, PFS, relapse rates and 1-year non-relapse mortality (NRM) were 63%, 59%, 21% and 20%, respectively. Uncontrolled disease status and high hematopoietic cell transplantation comorbidity index (HCT-CI) were associated with lower OS, whereas PBSC was an independent protective factor. Uncontrolled disease and HCT-CI >2 was predictive for NRM. Finally, disease status other than CR was predictive of relapse. In conclusion, haplo-HSCT is a valid treatment in advanced HL, offering excellent rates of survival and acceptable toxicities.
Assuntos
Ciclofosfamida/uso terapêutico , Doença de Hodgkin/terapia , Transplante Haploidêntico/métodos , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Doença de Hodgkin/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico , Prognóstico , Análise de Sobrevida , Transplante Haploidêntico/mortalidade , Adulto JovemRESUMO
Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.
Assuntos
Ciclofosfamida/uso terapêutico , Doença de Hodgkin/terapia , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro , Antígenos HLA , Histocompatibilidade , Doença de Hodgkin/mortalidade , Humanos , Masculino , Estudos Retrospectivos , Transplante de Células-Tronco/normas , Transplante Homólogo , Doadores não Relacionados/provisão & distribuiçãoRESUMO
The clinical outcome of primary refractory (PRF) AML patients is poor and only a minor proportion of patients is rescued by allogenic hematopoietic stem cell transplantation (HSCT). The identification of pre-HSCT variables may help to determine PRF AML patients who can most likely benefit from HSCT. We analyzed PRF AML patients transplanted between 1999 and 2012 from a sibling, unrelated donor or a cord blood unit. Overall, 227 patients from 26 Gruppo Italiano Trapianto di Midollo Osseo e Terapia cellulare centers were included in the analysis. At 3 years, the overall survival was 14%. By multivariate analysis, the number of chemotherapy cycles, (hazard ratio (HR): 1.87; 95% confidence interval (CI): 1.24-2.85; P=0.0028), the percentage of bone marrow or peripheral blood blasts (HR: 1.75; 95% CI: 1.16-2.64; P=0.0078), the adverse cytogenetic (HR: 1.44; 95% CI: 1.00-2.07; P=0.0508) and the age of patients (HR: 1.77; 95% CI: 1.08-2.88; P=0.0223) remained significantly associated with survival. Thus, we set up a new score predicting at 3 years after transplantation, an overall survival probability of 32% for patients with score 0 (no or 1 prognostic factor), 10% for patients with score 1 (2 prognostic factors) and 3% for patients with score 2 (3 or 4 prognostic factors).
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Irmãos , Doadores não Relacionados , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaAssuntos
Antineoplásicos Alquilantes/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Ciclofosfamida/uso terapêutico , Cistite/tratamento farmacológico , Cistite/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Polyomavirus/patogenicidade , Condicionamento Pré-Transplante/efeitos adversos , Antineoplásicos Alquilantes/farmacologia , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/farmacologia , Ciclofosfamida/farmacologia , Cistite/patologia , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodosRESUMO
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.
Assuntos
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 TratamentoAssuntos
Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Progressão da Doença , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto JovemAssuntos
Morte Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Doença de Hodgkin/tratamento farmacológico , Imunoconjugados/uso terapêutico , Mitose/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Brentuximab Vedotin , Sinergismo Farmacológico , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/farmacologiaAssuntos
Transplante de Medula Óssea , Transplante de Células-Tronco de Sangue Periférico , Células-Tronco/citologia , Condicionamento Pré-Transplante , Adolescente , Adulto , Fatores Etários , Idoso , Ensaios Clínicos Fase II como Assunto , Estudos de Coortes , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia/terapia , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Síndromes Mielodisplásicas/terapia , Fatores de Tempo , Transplante Homólogo , Resultado do TratamentoRESUMO
Multiple myeloma (MM) is the leading indication for autologous stem cell transplantation (ASCT) worldwide. The safety and efficacy of reducing hospital stay for MM patients undergoing ASCT have been widely explored, and different outpatient models have been proposed. However, there is no agreement on the criteria for selecting patients eligible for this strategy as well as the standards for their clinical management. On the basis of this rationale, the Italian Group for Stem Cell Transplantation (GITMO) endorsed a project to develop guidelines for the management of outpatient ASCT in MM, using evidence-based knowledge and consensus-formation techniques. An expert panel convened to discuss the currently available data on the practice of outpatient ASCT management and formulated recommendations according to the supporting evidence. Evidence gaps were filled with consensus-based statements. Three main topics were addressed: (1) the identification of criteria for selecting MM patients eligible for outpatient ASCT management; (2) the definition of standard procedures for performing outpatient ASCT (model, supportive care and monitoring during the aplastic phase); (3) the definition of the standard criteria and procedures for re-hospitalization during the aplastic phase at home. Herein, we report the summary and the results of the discussion and the consensus.
Assuntos
Consenso , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Pacientes Ambulatoriais , Guias de Prática Clínica como Assunto/normas , Transplante Autólogo , Protocolos Clínicos/normas , Conferências de Consenso como Assunto , Hospitalização , Humanos , Itália , Seleção de PacientesRESUMO
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.
Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Haploidêntico/efeitos adversos , Adolescente , Adulto , Idoso , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Several transplantation outcomes have been shown to be associated with the infused bone marrow cell dose/kg of the recipient's body weight. The donor bone marrow density is directly related to the infused cell dose. The aim of the present study was to identify donor-related variables that are associated with high donor bone marrow density. MATERIALS AND METHODS: We retrospectively analysed the predictive factors of high marrow density in 65 consecutive HLA-haploidentical bone marrow donors harvested at our centre between 2009 and 2013. RESULTS: Body mass index (BMI) and peripheral white blood cell (WBC) count were directly associated with bone marrow density (regression coefficient ß = 5·33 and ß = 2·93, respectively; P < 0·01). The likelihood of obtaining a collection with a high density was first predicted using BMI (BMI ≥30, mean density = 25·8 TNC/ml × 10(6) ). Second, donors with a BMI <30 were split into two groups according to peripheral WBC count (WBC <8 × 10(3) /mm(3) : mean density = 18·4 TNC/ml × 10(6) ; WBC ≥8 × 10(3) /mm(3) : mean density = 23·1 TNC/ml × 10(6) ). We also observed that the density of the first collected bag directly correlated with the overall density (R(2) = 0·69, P < 0·01). CONCLUSION: The donor-related features BMI and WBC count affect the cell quantity obtainable with the harvest and should be taken into account when choosing the donor.