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1.
Artigo em Inglês | MEDLINE | ID: mdl-34629467

RESUMO

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive hematological malignancy; however, some patients achieve durable remission with allogeneic hematopoietic cell transplantation (allo-HCT). We report on all 17 patients with BPDCN who underwent allo-HCT at our center between 2000 and 2020. The median age was 39 (18-67) years. All (n = 16, 94%), except one patient, had systemic disease involving bone marrow and/or other organs. Ten patients (59%) were in first complete remission (CR1) at allo-HCT. The donor source was matched related or unrelated in ten (59%) and alternate donor in seven (41%) patients. Five (31%) patients developed acute graft-versus-host disease (GVHD), all grade I-II. The cumulative incidence (CI) of chronic GVHD at five-year was 34%. The CI of non-relapse mortality at one-year was 29%. Progression-free survival (PFS) rates at two-year and five-year were 49% (95% CI = 22-71%) and 39% (95% CI = 14-64%), respectively. The two-year and five-year overall survival (OS) rates were 65% (95% CI = 38-82%) and 40% (95% CI = 12-68%), respectively. The five-year rate for both PFS and OS was 80% in CR1 patients versus 0% in patients not in CR1. In conclusion, allo-HCT provides long-lasting remissions in BPDCN patients, particularly when performed in CR1.

2.
Clin Cancer Res ; 27(21): 5847-5856, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34380640

RESUMO

PURPOSE: To compare outcomes between patients with relapsed follicular lymphoma who received a nonmyeloablative allogeneic stem cell transplant (alloSCT) and those who received an autologous transplant (autoSCT). PATIENTS AND METHODS: We evaluated 194 patients with follicular lymphoma who received an alloSCT (n = 98) or autoSCT (n = 96) at MD Anderson Cancer Center (Houston, TX). The transplant type used was based on donor availability and by Medicare reimbursement guidelines. Patients who received an alloSCT were enrolled in four consecutive trials in which they received fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning. autoSCT patients received R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan). RESULTS: The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for patients who received an alloSCT compared with those who received an autoSCT (62% vs. 46%; P = 0.048). Similarly, progression-free survival rates were 52% in patients who received an alloSCT and 31% in those who received an autoSCT (P < 0.001), and the 8-year relapse rates were 11% and 43%, respectively (P < 0.0001). Only three patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 to 4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Nonrelapse mortality was similar between the two groups (15% vs. 11% at 8 years; P = 0.27). CONCLUSIONS: This study shows that alloSCT is curative and confers superior survival compared with autoSCT in patients with follicular lymphoma.

3.
Transplant Cell Ther ; 27(5): 359-362, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965172

RESUMO

As an alternative stem cell source, cord blood (CB) has many advantages. However, delayed engraftment, lack of transferred immunity, and a significant incidence of acute graft-versus-host disease renders CB transplant (CBT) recipients at high risk of infectious complications. This guidance written by CBT and infectious disease experts outlines evidence-based recommendations for the prevention and treatment of opportunistic infections in adult patients undergoing CBT. Topics addressed include bacterial, fungal, viral, pneumocystis jirovcii and toxoplasmosis prophylaxis, suggested PCR monitoring for viruses, therapy for the most commonly encountered infections after CBT. We review key concepts including the recent important role of letermovir in the prevention of CMV reactivation. In instances where there is a paucity of data, practice recommendations are provided, including the duration of antimicrobial prophylaxis.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Infecções Oportunistas , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Humanos , Infecções Oportunistas/tratamento farmacológico
4.
Bone Marrow Transplant ; 56(8): 2005-2012, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33846563

RESUMO

Despite low nonrelapse mortality (NRM) at day 100 after allogeneic hematopoietic cell transplantation (HCT), NRM at 1 year remains substantial. In this study, we retrospectively analyzed 199 patients who were treated on a phase II clinical trial assessing safety and efficacy of myeloablative fractionated busulfan and fludarabine conditioning regimen for hematologic malignancies. The goal of the study was to identify factors associated with NRM occurring between days 101 and 365 post-HCT and generate a hypothesis for future studies to reduce the risk of NRM at 1 year. We found that a vast majority (83%) of patients who experienced NRM between days 101 and 365 had prior grade II-IV acute graft-versus-host disease (GVHD), which was the leading cause of death either by itself (33.3%) or complicated by infections (37.5%). In multivariate analysis, grade II-IV acute GVHD (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.3-6.6, p = 0.01) was the only significant predictor of NRM between days 101 and 365. Measures to reduce the risk of acute GVHD could lower the risk of NRM at 1 year and improve overall survival.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Bussulfano , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo
5.
Cancer ; 127(10): 1598-1605, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33471943

RESUMO

BACKGROUND: A myeloablative conditioning regimen can be safely given to older patients and those with comorbidities without increasing nonrelapse mortality (NRM) by fractionating the dose of intravenous busulfan. How this approach compares in efficacy with traditional, nonfractionated, lower dose regimens is unknown. METHODS: Outcomes were compared in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome who received either myeloablative, fractionated busulfan (f-Bu) dosed to achieve an area under the curve of 20,000 µmol per minute (f-Bu20K) over 2 weeks (n = 84) or a standard, nonfractionated, lower busulfan dose regimen of 16,000 µmol per minute (Bu16K) over 4 days (n = 78). Both groups also received fludarabine 40 mg/m2 intravenously for 4 days. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Patients in the Bu16K group who had unrelated donors also received antithymocyte globulin. The primary endpoint was progression-free survival. RESULTS: Roughly one-half of the patients were aged >65 years, approximately 40% had poor-risk cytogenetics, approximately 40% of those with AML were not in complete remission, and approximately 40% had a comorbidity index >3. At 2 years, progression-free survival was significantly improved in the f-Bu20K group compared with the Bu16K group (45% vs 24%, respectively; hazard ratio [HR], 0.6; 95% CI, 0.4-0.8; P = .004). This was because of a significant reduction in progression (34% vs 59%, respectively; HR, 0.5; 95% CI, 0.3-0.8; P = .003) without any increase in NRM (21% vs 15%, respectively; HR, 1.4; 95% CI, 0.7-3; P = .3), which resulted in improved overall survival (51% vs 31%, respectively; HR, 0.6; 95% CI, 0.3-0.9; P = .01). CONCLUSIONS: A myeloablative, fractionated busulfan regimen reduces relapse and improves survival without increasing NRM in older patients with AML and myelodysplastic syndrome.

6.
Acta Haematol ; 144(1): 74-81, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32604096

RESUMO

Acute myeloid leukemia (AML) patients not in remission and beyond first or second complete remission are considered allogeneic stem cell transplant (SCT) candidates. We present 361 patients who underwent SCT from matched related or unrelated donors between 2005 and 2013. The purpose was to identify a subgroup of patients with active disease at the time of transplant that benefit. Cox proportional hazards regression analysis was used for univariate and multivariate analyses to predict overall survival (OS). Variables considered were age, sex, SWOG cytogenetic risk group, bone marrow (BM) and peripheral blood (PB) blast percentage, regimen intensity, and type of AML. At a median of 26 months after transplantation, OS, progression-free survival (PFS), non-relapse mortality, and relapse rates were 26, 24, 23, and 48%, respectively. In a univariate analysis, risk cytogenetics (p < 0.001) and BM blasts >4% (p = 0.006) or any blasts in PB (p < 0.001) indicated worse OS. In a multivariate analysis, patients with <5% BM blasts or absence of circulating blasts and good or intermediate risk cytogenetics had significantly superior OS (46%), PFS (44%), and disease progression at 3 years. Based on these findings, patients not in remission with good or intermediate risk cytogenetics and low blast counts should be considered for SCT.


Assuntos
Medula Óssea/patologia , Aberrações Cromossômicas , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais , Biópsia , Análise Citogenética , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
7.
Biol Blood Marrow Transplant ; 25(7): 1347-1354, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30826465

RESUMO

Although bortezomib and rituximab have synergistic activity in patients with lymphoma and both can attenuate graft-versus-host disease (GVHD), the drugs have not been used together in patients undergoing allogeneic stem cell transplantation (alloSCT). In this phase I/II trial, we assessed the safety and activity of bortezomib added to the rituximab (R) plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. Bortezomib (1 to 1.3 mg/m2 per dose) was administered i.v. on days -13, -6, -1, and +2. We performed inverse probability weighting analysis to compare GVHD and survival results with an historical control group that received R-BEAM without bortezomib. Thirty-nine patients were assessable for toxic effects and response. The median age was 54 years. The most common diagnosis was diffuse large B cell lymphoma (41%). Twenty-two patients (56%) and 17 patients (44%) received their transplants from matched related and matched unrelated donors, respectively. The maximum tolerated bortezomib dose was 1 mg/m2. The weighted cumulative incidences of grades II to IV and III or IV acute GVHD were 50% and 34%, respectively; these incidences and survival rates were not significantly different from those of the control group. Median survival was not reached in patients age ≤ 50 years and with a long follow-up time of 60.7 months. The R-BEAM regimen has a survival benefit in lymphoma patients age ≤ 50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bortezomib/administração & dosagem , Neoplasias Hematológicas , Linfoma Difuso de Grandes Células B , Rituximab/administração & dosagem , Transplante de Células-Tronco , Adulto , Fatores Etários , Idoso , Aloenxertos , Carmustina/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Podofilotoxina/administração & dosagem , Taxa de Sobrevida
8.
Bone Marrow Transplant ; 53(3): 315-325, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29269797

RESUMO

We report outcomes of 60 patients with steroid-refractory (SR)-aGVHD treated with pentostatin. Almost half (47%) of patients had grade 4 GVHD-22% had stage 3-4 liver GVHD and 51% had stage 3-4 lower gastrointestinal tract (LGI) GVHD. Patients received a median of 3 courses (range, 1-9) of pentostatin. Day 28 overall response rate (ORR) was 33% (n = 20) (complete response 18% (n = 11), partial response 15% (n = 9)). Non-relapse mortality was 72% (95% confidence interval (CI) 61-84%) and overall survival (OS) was 21% (95% CI 12-32%) at 18 months. On univariate analysis, age >60 years (HR 1.9, 95% CI 1.01-3.7, p = 0.045) and presence of liver GVHD (HR 1.9, 95% CI 1.9, 95% CI 1.5-3.3, p = 0.03) were significant predictors of poor OS while patients with LGI GVHD had superior OS than those without (HR 0.4, 95% CI 0.2-0.8, p = 0.01). On stratified analysis, patients <60 years with isolated LGI GVHD had the best outcomes with an ORR of 48% and OS of 42% at 18 months. Among older patients, OS was 14% in those with isolated LGI aGVHD and 0% in others. Pentostatin remains a viable treatment option for SR-aGVHD, especially in patients 60 years or younger with isolated LGI involvement.


Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Seleção de Pacientes , Pentostatina/uso terapêutico , Terapia de Salvação/métodos , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Feminino , Gastroenteropatias , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Hepatopatias , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Esteroides , Análise de Sobrevida , Adulto Jovem
9.
Future Oncol ; 13(9): 821-831, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27908206

RESUMO

Mesenchymal stem cells (MSCs) have long been used as therapeutic agents in disease affecting various organ systems. However, MSCs are fast emerging as promising anticancer agents which have the potential to treat a number of different cancer types, including glioblastoma and metastatic breast, ovarian and hepatic carcinoma. The ability of MSC to migrate directly into the tumor microenvironment and to produce IFN-α and -ß makes this possible. However, the possibility of MSC undergoing either malignant transformation or transformation into protumorigenic fibroblasts currently limits their role in clinical use. It is hoped that future research can overcome these limitations and facilitate the use of MSC clinically.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Neoplasias/terapia , Medicina Regenerativa , Animais , Movimento Celular , Citocinas/metabolismo , Terapia Genética/métodos , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias/metabolismo , Neoplasias/patologia , Transdução Genética , Transgenes , Microambiente Tumoral
11.
Cytotherapy ; 17(6): 796-802, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25819838

RESUMO

Regenerative medicine offers new hope for many debilitating diseases that result in damage to tissues and organs. The concept is straightforward with replacement of damaged cells with new functional cells. However, most tissues and organs are complex structures involving multiple cell types, supportive structures, a microenvironment producing cytokines and growth factors and a vascular system to supply oxygen and other nutrients. Therefore repair, particularly in the setting of ischemic damage, may require delivery of multiple cell types providing new vessel formation, a new microenvironment and functional cells. The field of stem cell biology has identified a number of stem cell sources including embryonic stem cells and adult stem cells that offer the potential to replace virtually all functional cells of the body. The focus of this article is a discussion of the potential of mesenchymal stromal cells (MSCs) from cord blood (CB) for regenerative medicine approaches.


Assuntos
Sangue Fetal/citologia , Células-Tronco Mesenquimais/citologia , Ensaios Clínicos como Assunto , Humanos , Transplante de Células-Tronco Mesenquimais , Nicho de Células-Tronco
12.
Biol Blood Marrow Transplant ; 20(6): 787-93, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24548875

RESUMO

Cord blood transplantation (CBT) is a known risk factor for human herpesvirus-6 (HHV-6) infection. We analyzed the nature of HHV-6 infections in 125 double-unit CBT recipients (median age, 42 years) transplanted for hematologic malignancies with calcineurin inhibitor/mycophenolate mofetil prophylaxis and no antithymocyte globulin. One hundred seventeen patients (94%) reactivated HHV-6 by quantitative plasma PCR (median peak, 7600 copies/mL; range, 100 to 160,000) at a median of 20 days (range, 10 to 59) after transplantation. HHV-6 encephalitis occurred in 2 patients (1.6%), of whom 1 died and 1 recovered with therapy. No association was found between high-level HHV-6 viremia (≥10,000 or ≥25,000 copies/mL) and age, diagnosis, conditioning intensity, or dominant unit characteristics or between high-level viremia and transplant outcomes (engraftment, cytomegalovirus reactivation, day 100 grades II to IV acute graft-versus-host disease, day 100 transplant-related mortality, or 1-year disease-free survival). HHV-6 therapy delayed the onset of cytomegalovirus reactivation. Interestingly, HHV-6 resolution was observed in untreated patients, and resolution of viremia correlated with absolute lymphocyte count recovery. We observed a low incidence of encephalitis and no association with CBT outcomes. Our data suggest therapy in uncomplicated viremia may not be warranted. However, further investigation of the risk-to-benefit of HHV-6 viremia treatment and standardization of PCR testing is required.


Assuntos
Soro Antilinfocitário/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Encefalite Viral/etiologia , Herpesvirus Humano 6/isolamento & purificação , Infecções por Roseolovirus/etiologia , Viremia/virologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Encefalite Viral/virologia , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Infecções por Roseolovirus/virologia , Adulto Jovem
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