RESUMO
T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Prolinfocítica de Células T , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Prolinfocítica de Células T/terapia , Pessoa de Meia-Idade , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversosRESUMO
PURPOSE: There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor. METHODS: We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant. RESULTS: In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group. CONCLUSION: Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Idoso , Doença Crônica , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Feminino , Doença Enxerto-Hospedeiro , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Adulto JovemRESUMO
Hematopoietic cellular transplantation (HCT) has impacted medicine beyond simply treating certain diseases. Allogeneic HCT was the first documented successful immunological cellular therapy. Its usage continues to increase. The immunological disparity between donor and recipient has been associated with better antitumor efficacy as well as immunological toxicities. Through active clinical trials and research, considerable improvements in HCT therapy have been made over the past 50 years. The HCT international outcomes registry has considerably contributed to these improvements by identifying factors that could never be studied by a single center. With the use of unrelated donors, international collaboration increased as donor cell access through registries was not inhibited by international boundaries. HCT as a field pioneered the development of organizations for self-regulation that were assessing the entire program as an integrated whole rather than simply assessing facilities and providers separately.
RESUMO
Importance: In 2010, the US Centers for Medicare & Medicaid Services (CMS) indicated that data regarding efficacy of allogeneic hematopoietic stem cell transplantation (HCT) in the CMS beneficiary population with myelodysplastic syndrome (MDS) were currently insufficient, but that coverage would be provided for patients enrolled in a clinical study that met its criteria for Coverage with Evidence Development (CED). Objective: The Center for International Bone Marrow Transplant Research (CIBMTR) submitted a study concept comparing the outcomes of patients aged 55 to 64 years vs aged 65 years or older who met those criteria, effectively providing coverage by CMS for HCT for MDS. Design, Setting, and Participants: Data on patients aged 65 years or older were prospectively collected and their outcomes compared with patients aged 55 to 64 years. Patients were enrolled in the study from December 15, 2010, to May 14, 2014. The results reported herein were analyzed as of September 4, 2017, with a median follow-up of 47 months. The study was conducted by the CIBMTR. It comprises a voluntary working group of more than 420 centers worldwide that contribute detailed data on allogeneic and autologous HCT and cellular therapies. Interventions: Patients with MDS received HCT according to institutional guidelines and preferences. Main Outcomes and Measures: The primary outcome was overall survival (OS); secondary outcomes included nonrelapse mortality (NRM), relapse-free survival, and acute and chronic graft vs host disease. Results: During the study period, 688 patients aged 65 years or older underwent HCT for MDS and were compared with 592 patients aged 55 to 64 years. Other than age, there were no differences in patient and disease characteristics between the groups. On univariate analysis, the 3-year NRM rate was 28% vs 25% for the 65 years or older group vs those aged 55 to 64 years, respectively. The 3-year OS was 37% vs 42% for the 65 years or older group vs the 55 to 64 years age group, respectively. On multivariable analysis after adjusting for excess risk of mortality in the older group, age group had no significant association with OS (HR, 1.09; 95% CI, 0.94-1.27; P = .23) or NRM (HR, 1.19; 95% CI, 0.93-1.52; P = .16). Conclusions and Relevance: Older patients with MDS undergoing HCT have similar OS compared with younger patients. Based on current data, we would recommend coverage of HCT for MDS by the CMS. Trial Registration: ClinicalTrials.gov identifier: NCT01166009.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Recidiva Local de Neoplasia/terapia , Transplante Homólogo , Adulto , Fatores Etários , Idoso , Feminino , Doença Enxerto-Hospedeiro , Humanos , Masculino , Medicare , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/patologia , Estados UnidosRESUMO
Allogeneic bone marrow transplantation (BMT) is curative therapy for the treatment of patients with severe aplastic anemia (SAA). However, several conditioning regimens can be used for BMT. We evaluated transplant conditioning regimens for BMT in SAA after HLA-matched sibling and unrelated donor BMT. For recipients of HLA-matched sibling donor transplantation (n = 955), fludarabine (Flu)/cyclophosphamide (Cy)/antithymocyte globulin (ATG) or Cy/ATG led to the best survival. The 5-year probabilities of survival with Flu/Cy/ATG, Cy/ATG, Cy ± Flu, and busulfan/Cy were 91%, 91%, 80%, and 84%, respectively (P = .001). For recipients of 8/8 and 7/8 HLA allele-matched unrelated donor transplantation (n = 409), there were no differences in survival between regimens. The 5-year probabilities of survival with Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG/total body irradiation 200 cGy, Flu/Cy/ATG, and Cy/ATG were 77%, 80%, 75%, and 72%, respectively (P = .61). Rabbit-derived ATG compared with equine-derived ATG was associated with a lower risk of grade II to IV acute graft-versus-host disease (GVHD) (hazard ratio [HR], 0.39; P < .001) but not chronic GVHD. Independent of conditioning regimen, survival was lower in patients aged >30 years after HLA-matched sibling (HR, 2.74; P < .001) or unrelated donor (HR, 1.98; P = .001) transplantation. These data support Flu/Cy/ATG and Cy/ATG as optimal regimens for HLA-matched sibling BMT. Although survival after an unrelated donor BMT did not differ between regimens, use of rabbit-derived ATG may be preferred because of lower risks of acute GVHD.
Assuntos
Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Transplante de Medula Óssea , Condicionamento Pré-Transplante , Adolescente , Adulto , Anemia Aplástica/mortalidade , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Tomada de Decisão Clínica , Gerenciamento Clínico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/genética , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Humanos , Prognóstico , Índice de Gravidade de Doença , Irmãos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Allogeneic hematopoietic cell transplantation (alloHCT) is offered in a limited number of medical centers and is associated with significant direct and indirect costs. The degree to which social and geographic barriers reduce access to alloHCT is unknown. Data from the Surveillance, Epidemiology and End Results Program (SEER) and the Center for International Blood and Marrow Transplant Research (CIBMTR) were integrated to determine the rate of unrelated donor (URD) alloHCT for acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS) performed between 2000 and 2010 in the 612 counties covered by SEER. The total incidence of AML, ALL, and MDS was determined using SEER, and the number of alloHCTs performed in the same time period and geographic area were determined using the CIBMTR database. We then determined which sociodemographic attributes influenced the rate of alloHCT (rural/urban status, median family size, percentage of residents below the poverty line, and percentage of minority race). In the entire cohort, higher levels of poverty were associated with lower rates of alloHCT (estimated rate ratio [ERR], .86 for a 10% increase in the percentage of the population below the poverty line; P < .01), whereas rural location was not (ERR, .87; Pâ¯=â¯.11). Thus, patients from areas with higher poverty rates diagnosed with ALL, AML, and MDS are less likely patients from wealthier counties to undergo URD alloHCT. There is need to better understand the reasons for this disparity and to encourage policy and advocacy efforts to improve access to medical care for all.
Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Feminino , Humanos , Masculino , Transplante HomólogoRESUMO
We report graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) (a composite end point of survival without grade III-IV acute GVHD [aGVHD], systemic therapy-requiring chronic GVHD [cGVHD], or relapse) and cGVHD-free relapse-free survival (CRFS) among pediatric patients with acute leukemia (n = 1613) who underwent transplantation with 1 antigen-mismatched (7/8) bone marrow (BM; n = 172) or umbilical cord blood (UCB; n = 1441). Multivariate analysis was performed using Cox proportional hazards models. To account for multiple testing, P < .01 for the donor/graft variable was considered statistically significant. Clinical characteristics were similar between UCB and 7/8 BM recipients, because most had acute lymphoblastic leukemia (62%), 64% received total body irradiation-based conditioning, and 60% received anti-thymocyte globulin or alemtuzumab. Methotrexate-based GVHD prophylaxis was more common with 7/8 BM (79%) than with UCB (15%), in which mycophenolate mofetil was commonly used. The univariate estimates of GRFS and CRFS were 22% (95% confidence interval [CI], 16-29) and 27% (95% CI, 20-34), respectively, with 7/8 BM and 33% (95% CI, 31-36) and 38% (95% CI, 35-40), respectively, with UCB (P < .001). In multivariate analysis, 7/8 BM vs UCB had similar GRFS (hazard ratio [HR], 1.12; 95% CI, 0.87-1.45; P = .39), CRFS (HR, 1.06; 95% CI, 0.82-1.38; P = .66), overall survival (HR, 1.07; 95% CI, 0.80-1.44; P = .66), and relapse (HR, 1.44; 95% CI, 1.03-2.02; P = .03). However, the 7/8 BM group had a significantly higher risk for grade III-IV aGVHD (HR, 1.70; 95% CI, 1.16-2.48; P = .006) compared with the UCB group. UCB and 7/8 BM groups had similar outcomes, as measured by GRFS and CRFS. However, given the higher risk for grade III-IV aGVHD, UCB might be preferred for patients lacking matched donors.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Alemtuzumab/uso terapêutico , Células da Medula Óssea/citologia , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Sangue Fetal/citologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Modelos de Riscos Proporcionais , Recidiva , Taxa de Sobrevida , Tireoglobulina/uso terapêutico , Condicionamento Pré-Transplante , Irradiação Corporal TotalRESUMO
Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14â¯×â¯107 cells/kg identified MSD/low CD3+ (nâ¯=â¯223) and MSD/high CD3+ (nâ¯=â¯1214), and a dose of 15â¯×â¯107 cells/kg identified MUD/low CD3+ (nâ¯=â¯197) and MUD/high CD3+ (nâ¯=â¯1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; Pâ¯=â¯.009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; Pâ¯=â¯.04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (Pâ¯=â¯.10 and .07, respectively) or cGVHD (Pâ¯=â¯.80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.
Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Doença Enxerto-Hospedeiro , Leucemia , Síndromes Mielodisplásicas , Transplante de Células-Tronco de Sangue Periférico , Doença Aguda , Adolescente , Adulto , Aloenxertos , Relação CD4-CD8 , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA , Humanos , Leucemia/sangue , Leucemia/mortalidade , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Recidiva , Taxa de SobrevidaRESUMO
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and non-malignant diseases. Despite increasing survival rates, long-term morbidity following HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction following HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction following HCT. In this review, we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and to help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Lastly, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae following HCT.
Assuntos
Disfunção Cognitiva/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/terapia , Humanos , Efeitos Adversos de Longa Duração , Qualidade de Vida , Fatores de Risco , TransplantadosRESUMO
Hematopoietic cell transplantation (HCT) is a potentially curative treatment for children and adults with malignant and nonmalignant diseases. Despite increasing survival rates, long-term morbidity after HCT is substantial. Neurocognitive dysfunction is a serious cause of morbidity, yet little is known about neurocognitive dysfunction after HCT. To address this gap, collaborative efforts of the Center for International Blood and Marrow Transplant Research and the European Society for Blood and Marrow Transplantation undertook an expert review of neurocognitive dysfunction after HCT. In this review we define what constitutes neurocognitive dysfunction, characterize its risk factors and sequelae, describe tools and methods to assess neurocognitive function in HCT recipients, and discuss possible interventions for HCT patients with this condition. This review aims to help clinicians understand the scope of this health-related problem, highlight its impact on well-being of survivors, and help determine factors that may improve identification of patients at risk for declines in cognitive functioning after HCT. In particular, we review strategies for preventing and treating neurocognitive dysfunction in HCT patients. Finally, we highlight the need for well-designed studies to develop and test interventions aimed at preventing and improving neurocognitive dysfunction and its sequelae after HCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Neurocognitivos/etiologia , Biomarcadores , Humanos , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/prevenção & controle , Transtornos Neurocognitivos/terapia , Prevalência , Fatores de RiscoRESUMO
Patient-centered medical home models are fundamental to the advanced alternative payment models defined in the Medicare Access and Children's Health Insurance Plan Reauthorization Act (MACRA). The patient-centered medical home is a model of healthcare delivery supported by alternative payment mechanisms and designed to promote coordinated medical care that is simultaneously patient-centric and population-oriented. This transformative care model requires shifting reimbursement to include a per-patient payment intended to cover services not previously reimbursed such as disease management over time. Payment is linked to quality measures, including proportion of care delivered according to predefined pathways and demonstrated impact on outcomes. Some medical homes also include opportunities for shared savings by reducing overall costs of care. Recent proposals have suggested expanding the medical home model to specialized populations with complex needs because primary care teams may not have the facilities or the requisite expertise for their unique needs. An example of a successful care model that may provide valuable lessons for those creating specialty medical home models already exists in many hematopoietic cell transplantation (HCT) centers that deliver multidisciplinary, coordinated, and highly specialized care. The integration of care delivery in HCT centers has been driven by the specialty care their patients require and by the payment methodology preferred by the commercial payers, which has included bundling of both inpatient and outpatient care in the peritransplant interval. Commercial payers identify qualified HCT centers based on accreditation status and comparative performance, enabled in part by center-level comparative performance data available within a national outcomes database mandated by the Stem Cell Therapeutic and Research Act of 2005. Standardization across centers has been facilitated via voluntary accreditation implemented by Foundation for the Accreditation of Cell Therapy. Payers have built on these community-established programs and use public outcomes and program accreditation as standards necessary for inclusion in specialty care networks and contracts. Although HCT centers have not been described as medical homes, most HCT providers have already developed the structures that address critical requirements of MACRA for medical homes.
Assuntos
Transplante de Células-Tronco Hematopoéticas/economia , Administração dos Cuidados ao Paciente/tendências , Atenção à Saúde/economia , Atenção à Saúde/métodos , Humanos , Administração dos Cuidados ao Paciente/economia , Equipe de Assistência ao Paciente/tendências , Qualidade da Assistência à Saúde/normas , Reembolso de Incentivo/economiaAssuntos
Autofagia/efeitos dos fármacos , Hidroxicloroquina/farmacologia , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Inibidores de Proteínas Quinases/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Recidiva , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post-transplantation. METHODS: We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post-HCT using Poisson models. We also compared the incidence of grade 2-4 acute and chronic graft-versus-host disease (GVHD) in allogeneic HCT. RESULTS: The study included 1116 (15%) patients with pre-transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre-transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04-1.23; P = 0.004) and a higher incidence of grade 2-4 acute GVHD (HR, 1.25; 95% CI, 1.14-1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre-transplant depression was associated with fewer days-alive-and-out-of-the hospital (means ratio [MR] = 0.97; 95% CI, 0.95-0.99; P = 0.004). There were 512 (13.5%) patients with Pre-transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre-transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98-1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97-0.99; P = 0.002). CONCLUSION: Pre-transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre-transplant depression represent a population that is at risk for post-transplant complications. Cancer 2017;123:1828-1838. © 2017 American Cancer Society.
Assuntos
Depressão/psicologia , Transtorno Depressivo/psicologia , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Leucemia/terapia , Linfoma/terapia , Mieloma Múltiplo/terapia , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia/psicologia , Linfoma/psicologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/psicologia , Análise Multivariada , Síndromes Mielodisplásicas/psicologia , Prognóstico , Modelos de Riscos Proporcionais , Condicionamento Pré-Transplante , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Hematopoietic cell transplantation (HCT) survivors are at risk for development of late complications and require lifelong monitoring for screening and prevention of late effects. There is an increasing appreciation of the issues related to healthcare delivery and coverage faced by HCT survivors. The 2016 National Institutes of Health Blood and Marrow Transplant Late Effects Initiative included an international and broadly representative Healthcare Delivery Working Group that was tasked with identifying research gaps pertaining to healthcare delivery and to identify initiatives that may yield a better understanding of the long-term value and costs of care for HCT survivors. There is a paucity of literature in this area. Critical areas in need of research include pilot studies of novel and information technology supported models of care delivery and coverage for HCT survivors along with development and validation of instruments that capture patient-reported outcomes. Investment in infrastructure to support this research, such as linkage of databases including electronic health records and routine inclusion of endpoints that will inform analyses focused around care delivery and coverage, is required.
Assuntos
Transplante de Medula Óssea/métodos , Bases de Dados Factuais , Atenção à Saúde/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , National Institutes of Health (U.S.) , Projetos de Pesquisa , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/normas , Atenção à Saúde/tendências , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Efeitos Adversos de Longa Duração , Sobreviventes , Estados UnidosRESUMO
Over the past 2 decades, reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC HCT) has increased substantially. Many patients do not have fully HLA-matched donors, and the impact of HLA mismatch on RIC HCT has not been examined in large cohorts. We analyzed 2588 recipients of 8/8 HLA-high resolution matched (n = 2025) or single-locus mismatched (n = 563) unrelated donor (URD) RIC HCT from 1999 to 2011. Overall survival (OS) was the primary outcome. Secondary endpoints included treatment-related mortality (TRM), relapse, disease-free survival (DFS), and acute/chronic graft-versus-host disease (GVHD). Adjusted 1- and 3-year OS was better in 8/8- versus 7/8-matched recipients (54.7% versus 48.8%, P = .01, and 37.4% versus 30.9%, P = .005, respectively). In multivariate models 7/8 URD RIC HCT recipients had more grades II to IV acute GVHD (RR = 1.29, P = .0034), higher TRM (RR = 1.52, P < .0001), and lower DFS (RR = 1.12, P = .0015) and OS (RR = 1.25, P = .0001), with no difference in relapse or chronic GVHD. In subgroup analysis, inferior transplant outcomes were noted regardless of the HLA allele mismatched. Previously reported permissive mismatches at HLA-C (C*03:03/C*03:04) and HLA-DP1 (based on T cell-epitope matching) were not associated with better outcomes. Although feasible, single-locus mismatch in RIC URD HCT is associated with inferior outcomes.
Assuntos
Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Histocompatibilidade , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Teste de Histocompatibilidade , Humanos , Estimativa de Kaplan-Meier , Leucemia/mortalidade , Leucemia/terapia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Previous studies have shown that risks of collection-related pain and symptoms are associated with sex, body mass index, and age in unrelated donors undergoing collection at National Marrow Donor Program centers. We hypothesized that other important factors (race, socioeconomic status [SES], and number of procedures at the collection center) might affect symptoms in donors. We assessed outcomes in 2726 bone marrow (BM) and 6768 peripheral blood stem cell (PBSC) donors collected between 2004 and 2009. Pain/symptoms are reported as maximum levels over mobilization and collection (PBSC) or within 2 days of collection (BM) and at 1 week after collection. For PBSC donors, race and center volumes were not associated with differences in pain/symptoms at any time. PBSC donors with high SES levels reported higher maximum symptom levels 1 week after donation (P = .017). For BM donors, black males reported significantly higher levels of pain (OR, 1.90; CI, 1.14 to 3.19; P = .015). No differences were noted by SES group. BM donors from low-volume centers reported more toxicity (OR, 2.09; CI, 1.26 to 3.46; P = .006). In conclusion, race and SES have a minimal effect on donation-associated symptoms. However, donors from centers performing ≤ 1 BM collection every 2 months have more symptoms after BM donation. Approaches should be developed by registries and low-volume centers to address this issue.
Assuntos
Transplante de Medula Óssea , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Transplante de Células-Tronco de Sangue Periférico , Grupos Raciais , Classe Social , Doadores de Tecidos , Coleta de Tecidos e Órgãos/efeitos adversos , Adolescente , Adulto , Anestesia/efeitos adversos , Anestesia/métodos , Contagem de Células Sanguíneas , Índice de Massa Corporal , Infecções por Citomegalovirus/epidemiologia , Feminino , Filgrastim/efeitos adversos , Humanos , Renda/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Dor/epidemiologia , Dor/etiologia , Doadores de Tecidos/estatística & dados numéricos , Adulto JovemRESUMO
Natural killer cells are regulated by killer cell immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of natural killer cell reactivity have been associated with improved outcomes after myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n = 612) lacking ≥ 1 KIR ligands experienced higher grade III to IV acute graft-versus-host disease (GVHD) (HR, 1.6; 95% CI, 1.16 to 2.28; P = .005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II to IV (HR, 1.4; P = .002) and III to IV acute GVHD (HR, 1.5; P = .01) compared with HLA-C2(+) patients. AML patients with KIR2DS1(+), HLA-C2 homozygous donors had greater treatment-related mortality compared with others (HR, 2.4; 95% CI, 1.4 to 4.2; P = .002) but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor-activating KIRs or centromeric KIR content or for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n = 297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT.
Assuntos
Genótipo , Antígenos HLA-C/genética , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Receptores KIR2DL1/genética , Condicionamento Pré-Transplante , Adulto , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
We conducted a multicenter, phase 1 dose escalation study evaluating the safety of the allogeneic multipotent adult progenitor cell (MAPC, MultiStem, Athersys, Inc., Cleveland, OH) stromal product administered as an adjunct therapy to 36 patients after myeloablative allogeneic hematopoietic cell transplantation (HCT). Patients received increasing doses of MAPC (1, 5, or 10 million cells per kilogram recipient weight) as a single i.v. dose on day +2 after HCT (n = 18), or once weekly for up to 5 doses (1 or 5 million cells per kilogram; n = 18). Infusional and regimen-related toxicities were assessed for 30 days after the last MAPC dose. Of 36 allogeneic HCT donors (17 related and 19 unrelated), 35 were 6/6 HLA matched. MAPC infusions were well tolerated without associated infusional toxicity, graft failure, or increased incidence of infection. Median times to neutrophil (n = 36) and platelet (n = 31) engraftment were 15 (range, 11 to 25) and 16 (range, 11 to 41) days, respectively. The overall cumulative incidences of grades II to IV and III and IV acute graft-versus-host disease (GVHD) at day 100 were 37% and 14%, respectively (n = 36). In the group that received the highest single MAPC dose (10 million cells/kg), day 100 incidence of grade II to IV GVHD was 11.1% (1 of 9) with no observed cases of grade III and IV GVHD. We found no evidence for MHC class II allogeneic antibody induction, although some patients showed an increase in serum anticlass I titers compared with baseline. MAPC contribution to blood chimerism was negligible. These phase I data support the safety of stromal stem cell therapy and suggest that MAPC should be tested prospectively as a novel therapeutic option for GVHD prophylaxis after HCT.
Assuntos
Células-Tronco Adultas/transplante , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Multipotentes/transplante , Doença Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The BuFluTBI conditioning regimen was designed with the primary goal of reducing non-relapse mortality (NRM) while maximizing primary disease control in patients ineligible for myeloablative conditioning. Patients with hematologic malignancies for whom limited long-term survival was expected with standard therapy were administered an outpatient conditioning regimen of busulfan 3.2 mg/kg IV on day -5, fludarabine 30 mg/m(2) IV on days -4, -3, -2, and 200 cGy of total body irradiation (TBI) followed by stem cell infusion from related or unrelated donors. GVHD prophylaxis included cyclosporine and mycophenolate mofetil. 147 patients were enrolled from 2005-2011; 59% with myeloid disease and 41% with lymphoid disease. The median age was 64, and the median comorbidity index (HCT-CI) score was 3. Overall survival (OS), with 3.2 years median follow-up, was 60% at 1 year and 48% at 2 years, with projected OS 37% at 5 years. Relapse rates were 29% at 1 year and 33% at 2 years, with relapse mortality of 13% at 1 year, and 20% at 2 years. Nonrelapse mortality (NRM) at 1 year was 27% and 33% at 2 years. 54% of patients developed grade II-IV aGVHD and 67% of patients developed cGVHD within 2 years. On multivariate analysis, HCT-CI score 4 or greater, pre-transplant KPS less than 90, delayed platelet engraftment of more than 15 days, and grade II-IV aGVHD were found to be independent predictors of poor survival. There was no difference in OS or PFS between lymphoid and myeloid malignancies. BuFluTBI is an efficacious NMA regimen, active in both myeloid and lymphoid disease, and is ideally suited for use in patients age 65 and older or with an HCT-CI of 4 or greater.