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1.
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.

4.
Biol Blood Marrow Transplant ; 26(5): 1013-1020, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32045652

RESUMO

Fluid overload (FO) grade ≥2 (more than 10% weight gain from baseline) has recently been recognized as an important toxicity associated with a high rate of nonrelapse mortality in recipients of allogeneic hematopoietic cell transplantation (AHCT). The causes for FO remain unclear. We hypothesized that endothelial damage, possibly due to treatments received prior to AHCT, may be associated with this toxicity and sought to determine whether the Endothelial Activation and Stress Index (EASIX) (defined as lactate dehydrogenase [U/L]â€ˆ× creatinine [mg/dL]/platelets [109 cells/L]) correlates with grade ≥2 FO in 2 cohorts of recipients of AHCT at our institution. We tested our hypothesis in a cohort of 145 consecutive recipients (study cohort) of AHCT transplant from HLA-haploidentical donors and validated the findings in a cohort of 449 (validation cohort) recipients of AHCT from HLA-matched donors who underwent transplantation between 2010 and 2015. Predictors of grade ≥2 FO were evaluated using competing risks regression in univariate analysis and classification and regression tree (CART) analysis in multivariate analysis. The cumulative incidence of grade ≥2 FO was estimated considering death as a competing risk. EASIX scores were evaluated based on log2-transformed values. Optimal predictive EASIX cutoff values were determined based on receiver operating characteristics curve analysis. Grade ≥2 FO occurred in 21% and 6% of the study and validation cohorts, respectively, with the majority of these cases being diagnosed before the day of AHCT. Median log2 EASIX score at admission was 2.4 (interquartile range [IQR], 1.3, 3.7) and 2.5 (IQR, 1.4, 3.9) in the 2 respective cohorts. In univariate analysis, high EASIX at admission was a significant predictor of grade ≥2 FO in the study (cutoff: 4.4, hazard ratio [HR] = 4.8, P < .001) and in the validation (cutoff: 4.3, HR = 4.8, P < .001) cohorts. The significant effect of EASIX persisted in multivariate CART analysis in the study (HR = 6.3, P < .001) and the validation (HR = 28, P = .002) cohorts. Additional predictors in multivariate analysis included body weight below 80 kg in recipients older than 55 years (HR = 4.5, P < .001) in the study cohort and diabetes (HR = 34, P = .001) and age >60 years (HR = 9.6, P = .04) in the validation cohort. At admission, the prevalence of EASIX score of >4.3 (18% versus 17%, P = .9) was not different between the diabetics and nondiabetics. EASIX score at admission is a significant predictor of grade ≥2 FO in recipients of AHCT from HLA-haploidentical or HLA-matched donors. Independently of EASIX, older patients with low weight were associated with increased risk of grade ≥2 FO for recipients of HLA-haploidentical transplants. For the HLA-matched cohort, diabetes and older age were associated with increased FO risk. These findings require validation in external cohorts.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Idoso , Estudos de Coortes , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Doadores de Tecidos , Transplante Homólogo
5.
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
6.
Clin Lymphoma Myeloma Leuk ; 18(1): e41-e50, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29277360

RESUMO

BACKGROUND: Extra-Nodal natural killer/T-cell lymphoma (ENKL) is a rare lymphoma representing approximately 5-10% of T-cell non-Hodgkin lymphomas diagnosed in the United States each year. Patients with advanced stage III/IV ENKL and relapsed refractory ENKL have a poor prognosis even despite aggressive therapy and stem cell transplantation (SCT). We conducted a review of the management of 37 patients with advanced-stage and relapsed/refractory ENKL in a predominantly non-Asian cohort evaluating both chemotherapy and SCT outcomes. PATIENTS AND METHODS: We evaluated clinical outcomes in all patients treated for advanced stage III/IV or relapsed/refractory ENKL at MD Anderson cancer center between 2000-2014. Next, we collected stem cell transplant data from four transplant institutions to further evaluate outcomes of both allogeneic (allo-SCT) and autologous (auto-SCT) stem cell transplantation in ENKL. RESULTS: OS and PFS were 73% and 45% at one year, and 30% and 19% at 3-years, respectively. SMILE chemotherapy was more effective in maintaining a CR compared to CHOP (83% vs 17%). Only achievement of CR was prognostic for OS (HR 0.245, p=0.002) and PFS (HR 0.072, p) CONCLUSION: Our results suggest that achievement of a CR is imperative in patients with advanced ENKL, and is desirable for any patient for whom auto-SCT is utilized. SMILE-based chemotherapy appeared effective in attaining a CR, and was also an effective salvage regimen. For patients attaining a first CR, auto-SCT should be strongly considered, but should definitely be utilized in patients attaining CR2. For patients with refractory disease, allo-SCT can be considered in a selected group of patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/tratamento farmacológico , Linfoma/terapia , Células T Matadoras Naturais/metabolismo , Transplante de Células-Tronco/métodos , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Estudos de Coortes , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Adulto Jovem
7.
Biol Blood Marrow Transplant ; 23(12): 2166-2171, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28844946

RESUMO

Fluid overload (FO) commonly occurs during hospitalization for allogeneic hematopoietic stem cell transplantation. We hypothesized that FO is associated with transplantation outcomes and evaluated this complication in 2 cohorts of patients. FO was graded based on post-transplantation weight gain, symptoms, and need for treatment, scored in real time by an independent team. The first cohort (study cohort; n = 145) underwent haploidentical transplantation for hematologic malignancies following a melphalan-based conditioning regimen. In univariate analysis, factors associated with day +100 nonrelapse mortality (NRM) were FO grade ≥2 (hazard ratio [HR], 15; 95% confidence interval [CI], 4.2 to 55; P < .001), creatinine >1 mg/dL (HR, 4.7; 95% CI, 1.6 to 14; P = .005), and age >55 years (HR, 4.5; 95% CI, 1.5 to 13; P = .008). In multivariate analysis, factors associated with day +100 NRM were FO grade ≥2 (HR, 13.1; 95% CI, 3.4 to 50; P < .001) and serum creatinine level >1 mg/dL at transplantation admission (HR, 3.5; 95% CI, 1.1 to 11; P = .03). These findings were verified in a separate cohort (validation cohort) of patients with acute myelogenous leukemia/myelodysplastic syndrome who underwent HLA-matched transplantation with busulfan-based conditioning (n = 449). In multivariate analysis, factors associated with day +100 NRM were FO grade ≥2 (HR, 34; 95% CI, 7.2 to 158; P < .001) and, in patients with FO grade <2, advanced disease status (HR, 5; 95% CI, 1.1 to 22; P = .03). A higher NRM translated to significantly poorer 1-year overall survival rates for patients with FO ≥2 than for patients without FO (70% versus 42%, P < .001 in the study cohort and 64% versus 38%, P < .001 in the validation cohort). In conclusion, FO grade ≥2 is strongly associated with higher NRM and shorter survival and should be considered an important prognostic factor in transplantation.


Assuntos
Líquidos Corporais , Edema/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ganho de Peso , Adolescente , Adulto , Idoso , Feminino , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Adulto Jovem
8.
Biol Blood Marrow Transplant ; 23(8): 1405-1410, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28495642

RESUMO

In patients with chronic lymphocytic leukemia (CLL), persistence of disease after allogeneic stem cell transplantation (alloSCT) can result in poor outcomes. In an effort to improve these outcomes, patients with persistent CLL who were 90 to 100 days beyond alloSCT with no evidence of graft-versus-host-disease (GVHD) were randomized to receive lenalidomide or standard care (withdrawal of immunosuppression followed by donor lymphocyte infusion). Lenalidomide was initiated at 5 mg every other day and increased to 10 mg daily, if tolerated, in each patient. Of 38 patients enrolled, 17 (45%) met the eligibility criteria for randomization. Of these 17 patients, 8 were randomized to undergo lenalidomide therapy. Five (62%) patients had to stop taking the drug because of toxicity. The main reason for drug discontinuation was acute GVHD in 43% of patients. This incidence was 11% in the patients who were randomized to not receive lenalidomide. With a median follow-up of 2.6 years, the median survival was 3.4 years for those receiving lenalidomide. This was not reached in patients randomized to not receive lenalidomide and in patients in complete remission who were not randomized. These results suggested that treatments other than lenalidomide are needed for persistent CLL after alloSCT.


Assuntos
Doença Enxerto-Hospedeiro , Leucemia Linfocítica Crônica de Células B , Transfusão de Linfócitos , Transplante de Células-Tronco , Talidomida/análogos & derivados , Doença Aguda , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Humanos , Lenalidomida , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Talidomida/administração & dosagem , Talidomida/efeitos adversos
9.
Br J Haematol ; 177(4): 567-577, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28295181

RESUMO

There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs. 52%, P < 0·001). Thirty-three patients were treated with immunomodulation for relapse post-alloSCT (immunosuppression withdrawal, n = 6, donor lymphocyte infusion, n = 27); 17 achieved complete response (CR), which predicted superior PFS (53 months vs. 10 months, P < 0·001) and survival (117 months vs. 30 months, P = 0·006). Relapsed patients with mixed chimerism had inferior response to immunomodulation; conversion to full donor chimerism was highly correlated both with CR and with the development of severe acute GVHD, which was fatal in 3/8 patients. Novel therapeutic strategies are required for patients with mixed T-cell chimerism post-alloSCT for CLL.


Assuntos
Quimerismo , Leucemia Linfocítica Crônica de Células B/terapia , Transplante de Células-Tronco/métodos , Linfócitos T/fisiologia , Adulto , Assistência ao Convalescente/métodos , Idoso , Métodos Epidemiológicos , Feminino , Sobrevivência de Enxerto/genética , Doença Enxerto-Hospedeiro/etiologia , Humanos , Imunossupressores/uso terapêutico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Transfusão de Linfócitos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Transplante de Células-Tronco/mortalidade , Transplante Homólogo , Resultado do Tratamento
10.
Leuk Lymphoma ; 58(2): 366-371, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27348707

RESUMO

Lymphoblastic lymphoma (LBL) is an aggressive lymphoma pathologically similar to lymphoblastic leukemia, but primarily presents with nodal or extra-medullary involvement. The aim of this study is to describe outcomes of patients undergoing stem cell transplantation (SCT) for LBL compared to historical data. Thirty-nine patients, of which 54% lacked complete remission (CR), received SCT for LBL between 1990 and 2015; 31 allogeneic and eight autologous. Overall survival (OS) and progression free survival (PFS) at three years for the entire cohort was 41%, the cumulative incidence (CI) of non-relapse mortality (NRM) was 18% at one year, and CI relapse mortality was 28% at one-year and 36% at three years; results similar to historical reports. On multivariate analysis, the use of total-body irradiation (TBI) based conditioning and transplantation in CR were independently predictive of OS and PFS. For patients requiring SCT for LBL, CR and TBI-based conditioning prior to allogeneic SCT may provide improved disease control.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Terapia Combinada , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Indução de Remissão , Retratamento , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
11.
Biol Blood Marrow Transplant ; 23(2): 285-292, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27816651

RESUMO

We investigated the long-term safety and disease control data obtained with i.v. busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). A total of 107 patients, median age 38 years (range, 19 to 64 years) received a matched sibling donor (n = 52) or matched unrelated donor (n = 55) transplant for ALL in first complete remission (n = 62), second complete remission (n = 28), or more advanced disease (n = 17). Nearly one-half of the patients had a high-risk cytogenetic profile as defined by the presence of t(9;22) (n = 34), t(4;11) (n = 4), or complex cytogenetics (n = 7). Clo 40 mg/m2 was given once daily, with each dose followed by pharmacokinetically dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic cell infusion after 2 days of rest. The Bu dose was based on the drug clearance as determined by a test Bu dose of 32 mg/m2. The target daily area under the curve was 5500 µmol/min for patients aged <60 years and 4000 µmol/min for patients aged >59 years. With a median follow-up of 3.3 years among surviving patients (range, 1 to 5.8 years), the 2-year progression-free survival (PFS) for patients undergoing HSCT in first complete remission (CR1), second complete remission (CR2), or more advanced disease was 62%, 34%, and 35%, respectively. The regimen was well tolerated, with nonrelapse mortality (NRM) of 10% at 100 days and 31% at 2 years post-HSCT. The incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) was 35% and 10%, respectively; 18% patients developed extensive chronic GVHD. The 2-year overall survival (OS) for patients undergoing HSCT in CR1, CR2, or more advanced disease was 70%, 57%, and 35%, respectively. Among 11 patients aged >59 years treated with reduced-dose Bu in CR1 (n = 7) or CR2 (n = 4), 4 remain alive and disease-free, with a median follow-up of 2.6 years (range, 2 to 4.7 years). Only the presence of minimal residual disease at the time of transplantation was associated with significantly worse PFS and OS in multivariate analysis. Our data indicate that the Clo-Bu combination provides effective disease control while maintaining a favorable safety profile. OS and NRM rates compare favorably with those for traditional myeloablative total body irradiation-based conditioning regimens.


Assuntos
Nucleotídeos de Adenina/administração & dosagem , Arabinonucleosídeos/administração & dosagem , Bussulfano/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Aloenxertos , Clofarabina , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Irradiação Corporal Total , Adulto Jovem
12.
Biol Blood Marrow Transplant ; 22(7): 1333-1337, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27064056

RESUMO

Forty patients (median age, 31 years; range, 20 to 63) with Hodgkin lymphoma underwent an allogeneic stem cell transplant with the gemcitabine-fludarabine-melphalan reduced-intensity conditioning regimen. Thirty-one patients (77%) had undergone a prior autologous stem cell transplant, with a median time to progression after transplant of 6 months (range, 1 to 68). Disease status at transplant was complete remission/complete remission, undetermined (n = 23; 57%), partial remission (n = 14; 35%), and other (n = 3; 8%). Twenty-six patients (65%) received brentuximab vedotin before allotransplant. The overall complete response rate before allotransplant was 65% in brentuximab-treated patients versus 42% in brentuximab-naive patients (P = .15). At the latest follow-up (October 2015) 31 patients were alive. The median follow-up was 41 months (range, 5 to 87). Transplant-related mortality rate at 3 years was 17%. Pulmonary, skin toxicities, and nausea were seen in 13 (33%), 11 (28%), and 37 (93%) patients, respectively. At 3 years, estimates for overall and progression-free survival were 75% (95% CI, 57% to 86%) and 54% (95% CI, 36% to 70%). Overall incidence for disease progression was 28% (95% CI, 16% to 50%). We believe the gemcitabine-fludarabine-melphalan regimen allows moderate dose intensification with acceptable morbidity and mortality. The inclusion of gemcitabine affected nausea, pulmonary, and likely skin toxicity. Exposure to brentuximab vedotin allowed more patients to reach allogeneic stem cell transplantation in complete remission. With over 50% of patients progression-free at 3 years, allogeneic stem cell transplantation with reduced-intensity conditioning remains an effective and relevant treatment option for Hodgkin lymphoma in the brentuximab vedotin era.


Assuntos
Desoxicitidina/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Melfalan/uso terapêutico , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adulto , Brentuximab Vedotin , Desoxicitidina/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/complicações , Doença de Hodgkin/mortalidade , Humanos , Imunoconjugados/uso terapêutico , Pneumopatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Indução de Remissão , Terapia de Salvação/efeitos adversos , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Dermatopatias/induzido quimicamente , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo , Vidarabina/uso terapêutico , Adulto Jovem
13.
Biol Blood Marrow Transplant ; 22(3): 493-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26497906

RESUMO

Haploidentical transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PTCy) is increasingly utilized for the treatment of lymphoma and almost exclusively with the nonmyeloablative fludarabine (Flu)/cyclophosphamide/total body irradiation (TBI) conditioning regimen. We present early results of a reduced-intensity (RIC) regimen utilizing fludarabine and melphalan (FM) for the treatment of advanced lymphoma. All patients with a diagnosis of lymphoma or chronic lymphocytic leukemia (CLL) who received Haplo-SCT at the University of Texas MD Anderson Cancer Center between 2009 and 2014 were reviewed (N = 22). Patients received Flu 160 mg/m(2) and melphalan 100 mg/m(2) to 140 mg/m(2) with thiotepa 5 mg/kg or 2 Gy TBI. Because of concerns of increased treatment-related mortality (TRM) with the melphalan 140 mg/m(2) regimen (FM140), a RIC regimen with melphalan 100 mg/m(2) (FM100) was devised. Rituximab was included for CD20(+) disease. Graft-versus-host disease prophylaxis consisted of PTCy 50 mg/kg on days +3 and + 4, tacrolimus, and mycophenolate mofetil. Sixty-eight percent of all patients were not in complete remission at the time of transplantation. The 2-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 54%, 1-year TRM was 19%, and the cumulative incidence of relapse at 2 years was 27%. Two-year PFS for Hodgkin lymphoma, non-Hodgkin lymphoma, and CLL/small lymphocytic lymphoma were 57%, 51%, and 75%. Patients treated with FM100 compared to FM140 had equivalent PFS (71% versus 37%, P = .246) and OS (71% versus 58%, P = .32). These early results establish Flu and melphalan 100 mg/m(2) with 2 Gy TBI or thiotepa 5 mg/kg as a very promising conditioning regimen for the treatment of advanced lymphoma with Haplo-SCT and PTCy.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma/mortalidade , Linfoma/terapia , Melfalan/administração & dosagem , Condicionamento Pré-Transplante , Adulto , Aloenxertos , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem
14.
Biol Blood Marrow Transplant ; 19(7): 1059-64, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23644077

RESUMO

For patients with acute lymphoblastic leukemia (ALL) who relapse after allogeneic hematopoietic stem cell transplantation (HSCT), treatment options are limited, and the clinical course and prognostic factors affecting outcome have not been well characterized. We retrospectively analyzed outcomes of 123 adult patients with ALL who relapsed after a first HSCT performed at our center between 1993 and 2011. First-line salvage included second HSCT (n = 19), donor lymphocyte infusion with or without prior chemotherapy (n = 11), radiation therapy (n = 6), cytoreductive chemotherapy (n = 30), mild chemotherapy (n = 27), or palliative care (n = 23), with median postrelapse overall survival (OS) of 10 months, 6.5 months, 3 months, 4 months, 4 months, and 1 month, respectively. Despite a complete remission rate of 38% after first-line salvage in the treated patients, the OS rate remained limited with 1- and 2- year OS rates of 17% (95% confidence interval, 13 to 29) and 10% (95% confidence interval, 6 to 20), respectively. On univariate analysis, adverse factors for OS included active disease at the time of first HSCT and short time to progression from first HSCT (<6 months). There was no difference in the 6-month survival postrelapse in patients with isolated extramedullary relapse (44%) compared with combined extramedullary and bone marrow relapse (29%) or those with isolated bone marrow relapse (34%) (P = .8). Our data provide more insight into the disease behavior and treatment outcomes of ALL at relapse after HSCT against which future trials may be compared.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Agonistas Mieloablativos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Feminino , Humanos , Transfusão de Linfócitos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento
17.
Biol Blood Marrow Transplant ; 17(3): 412-20, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20674757

RESUMO

We investigated the administration of intravenous (i.v.) busulfan (Bu) combined with melphalan (Mel) in patients with advanced lymphoid malignancies undergoing autologous stem cell transplantation. Bu 130 mg/m(2) was infused daily for 4 days, either as a fixed dose per body surface area (BSA), or to target an average daily area under the curve of 5000 µmol-min, determined by a test dose of i.v. Bu at 32 mg/m(2) given 48 hours prior to the high-dose regimen, followed by a rest day, followed by 2 daily doses of Mel at 70 mg/m(2). Stem cells were infused the following day. Eighty patients had i.v. Bu delivered per test dose guidance. The median daily systemic Bu exposure was 4867 µmol-min. One hundred two patients (Hodgkin lymphoma n = 49, non-Hodgkin lymphoma n = 12, multiple myeloma = 41) with a median age of 44 years (range: 19-65 years) were treated. The 2-year overall survival and progression-free survival rates were 85% and 57%, respectively, for patients with Hodgkin lymphoma, 67% and 64%, respectively, for patients with non-Hodgkin lymphoma, and 82% and 42%, respectively, for patients with multiple myeloma. The regimen was very well tolerated with treatment-related mortality at 100 days, 1 year, and 2 years of 1%, 3%, and 3%, respectively. Intravenous Bu-Mel was well tolerated. Disease control wa encouraging, and should be explored in larger phase II studies.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Bussulfano/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Transtornos Linfoproliferativos/terapia , Melfalan/uso terapêutico , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/farmacocinética , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/terapia , Humanos , Infusões Intravenosas , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/terapia , Transtornos Linfoproliferativos/tratamento farmacológico , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Índice de Gravidade de Doença , Análise de Sobrevida , Transplante Autólogo , Adulto Jovem
18.
Blood ; 113(18): 4144-52, 2009 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-19168784

RESUMO

In this study, we analyzed the long-term outcome of a risk-adapted transplantation strategy for mantle cell lymphoma in 121 patients enrolled in sequential transplantation protocols. Notable developments over the 17-year study period were the addition of rituximab to chemotherapy and preparative regimens and the advent of nonmyeloablative allogeneic stem cell transplantation (NST). In the autologous transplantation group (n = 86), rituximab resulted in a marked improvement in progression-free survival for patients who received a transplant in their first remission (where a plateau emerged at 3-8 years) but did not change the outcomes for patients who received a transplant beyond their first remission. In the NST group, composed entirely of patients who received a transplant beyond their first remission, durable remissions also emerged in progression-free survival at 5 to 9 years. The major determinants of disease control after NST were the use of a peripheral blood stem cell graft and donor chimerism of at least 95%, whereas the major determinant of death was immunosuppression for chronic graft-versus-host disease. Our results show that long-term disease-free survival in mantle cell lymphoma is possible after rituximab-containing autologous transplantation for patients in first remission and after NST for patients with relapsed or refractory disease.


Assuntos
Doença Enxerto-Hospedeiro/terapia , Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto/terapia , Condicionamento Pré-Transplante , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Linfoma de Célula do Manto/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores de Risco , Rituximab , Taxa de Sobrevida , Transplante Autólogo , Resultado do Tratamento
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