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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.
Cancer ; 127(18): 3381-3389, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34138471

RESUMO

BACKGROUND: The outcome of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone plus ofatumumab hyper-CVAD + ofatumumab (hyper-CVAD + ofatumumab) has not been compared with the outcome of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone plus ofatumumab hyper-CVAD plus rituximab (hyper-CVAD + Rituximab) in Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) in a randomized clinical trial. METHODS: The authors compared the outcomes of 69 patients treated with hyper-CVAD + ofatumumab and 95 historical-control patients treated with hyper-CVAD + Rituximab. Historical-control patients were treated with hyper-CVAD + Rituximab if they had CD20 expression ≥ 20%. Ofatumumab (day 1 of course 1, 300 mg intravenously; subsequent doses, 2000 mg intravenously) was administered on days 1 and 11 of courses 1 and 3 and on days 1 and 8 of courses 2 and 4 for a total of 8 doses. A propensity score analysis with inverse probability of treatment weighting (IPTW) was performed to adjust for baseline covariates between groups. RESULTS: The median event-free survival with stem cell transplantation (SCT) censoring was 33 and 65 months with hyper-CVAD + Rituximab and hyper-CVAD + ofatumumab, respectively (crude P = .064; IPTW P = .054). The median overall survival with SCT censoring was 52 months and not reached, respectively (crude P = .087; IPTW P = .097). CONCLUSIONS: Hyper-CVAD + ofatumumab was associated with better outcomes than hyper-CVAD + Rituximab among patients with newly diagnosed Philadelphia chromosome-negative ALL.

4.
Cancer ; 127(15): 2648-2656, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793964

RESUMO

BACKGROUND: The achievement of a 3-month complete molecular response (CMR) is a major prognostic factor for survival in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). However, 25% of patients relapse during therapy with tyrosine kinase inhibitors (TKIs). METHODS: The authors reviewed 204 patients with Ph-positive ALL who were treated between January 2001 and December 2018 using the combination of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) plus a TKI (imatinib, 44 patients [22%]; dasatinib, 88 patients [43%]; or ponatinib, 72 patients [35%]). Progression-free survival (PFS) was defined as the time from the start date of therapy to the date of relapse, death, or last follow-up. Overall survival (OS) was defined as the time from the start date of therapy to the date of death or last follow-up. RESULTS: Overall, a 3-month CMR was observed in 57% of patients, including 32% of those who received imatinib, 52% of those who received dasatinib, and 74% of those who received ponatinib. The median follow-up was 74 months (imatinib, 180 months; dasatinib, 106 months; ponatinib, 43 months). Among 84 patients in 3-month CMR, 17 (20%) proceeded to undergo allogeneic stem cell transplantation (ASCT). The 5-year PFS and OS rates were 68% and 72%, respectively. By multivariate analysis, ponatinib therapy was the only significant favorable independent factor predicting for progression (P = .028; hazard ratio, 0.388; 95% CI, 0.166-0.904) and death (P = .042; hazard ratio, 0.379; 95% CI, 0.149-0.966). ASCT was not a prognostic factor for PFS and OS by univariate analysis. CONCLUSIONS: In patients with Ph-positive ALL, ponatinib is superior to other types of TKIs in inducing and maintaining a CMR, thus preventing disease progression. ASCT does not improve outcome once a 3-month CMR is achieved.

5.
Cancer ; 127(12): 2025-2038, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33740268

RESUMO

BACKGROUND: The outcome of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. The combination of inotuzumab with low-intensity mini-hyper-CVD (mini-hyper-CVD; cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 × 4 doses) chemotherapy has shown encouraging results. The sequential addition of blinatumomab might improve outcome in patients with R/R ALL. METHODS: We used lower intensity chemotherapy, mini-hyper-CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m2 x 4 doses) compared to conventional hyper-CVAD. RESULTS: Ninety-six patients with a median age of 37 years (range, 18-87 years) were treated. Overall, 77 patients (80%) responded, 55 (57%) of whom achieved complete response. The overall measurable residual disease negativity rate among responders was 83%. Forty-four (46%) patients underwent later allogeneic stem cell transplantation. Veno-occlusive disease of any grade occurred in 10 (10%) patients. The rates were 13% with the original schedule and 3% with the use of lower-dose inotuzumab and sequential blinatumomab. With a median follow-up of 36 months, the median overall survival (OS) was 13.4 months, with 3-year OS rates of 33%. The 3-year OS rate for patients with CD22 expression ≥70% and without adverse cytogenetics (KMT2A rearrangements, low hypodiploidy/near triploidy) was 55%. CONCLUSION: The combination of inotuzumab and low-intensity mini-hyper-CVD chemotherapy with or without blinatumomab shows sustained efficacy in patients with R/R ALL.

6.
Bone Marrow Transplant ; 56(6): 1316-1324, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33398094

RESUMO

Steroids remain the initial therapy for acute graft-vs.-host disease (AGVHD). Strategies to improve response and minimize steroid exposure are needed. We report results of a randomized, adaptive, Bayesian-designed, phase II trial of prednisone with or without extracorporeal photopheresis (ECP) as an initial therapy for patients with newly diagnosed AGVHD. The primary endpoint was success at day 56 defined as: alive, in remission, achieving AGVHD response without additional therapy, and on <1 mg/kg at day 28 and <0.5 mg/kg on day 56 of steroids. Eighty-one patients were randomized to the ECP arm (n = 51) or steroids alone (n = 30). Median age was 54 years (range: 17-75); 90% had grade II AGVHD and 10% had grades III and IV AGVHD, with skin (85%), upper (22%)/lower (22%) gastrointestinal, and liver (10%) involvement. The ECP arm had a higher probability of success (0.815) and exceeded the predefined threshold for determining the investigational arm promising. ECP was potentially more beneficial than steroids-alone in skin-only AGVHD (response rate: 72% vs. 57%, respectively) than for visceral-organ AGVHD (47% vs. 43%, respectively). The addition of ECP to steroids may result in higher GVHD response as initial therapy for AGVHD, especially for patients with skin-only involvement.


Assuntos
Doença Enxerto-Hospedeiro , Fotoferese , Doença Aguda , Adolescente , Adulto , Idoso , Teorema de Bayes , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Esteroides/uso terapêutico , Adulto Jovem
8.
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
10.
Blood Adv ; 4(7): 1296-1306, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32236526

RESUMO

At our center, we observed a series of patients who developed transudative refractory ascites secondary to noncirrhotic, non-veno-occlusive disease (VOD)-related portal hypertension after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients were considered to have idiopathic portal hypertension-related refractory ascites (IRA) if they developed ascites secondary to intrahepatic portal hypertension (serum ascites albumin gradient ≥1.1 g/dL or hepatic venous pressure gradient [HVPG] >5 mm Hg), but did not meet the clinical criteria for classical VOD/sinusoidal obstructive syndrome (SOS) and did not have any alternate etiology of portal hypertension. From our institutional database, we identified 40 patients who developed IRA after allo-HSCT between 2004 and 2018. The patients' median age at the time of allo-HSCT was 54 years (range, 21-73 years). The median time to development of IRA after allo-HSCT was 80 days (range, 16-576 days). The median number of paracentesis was 3 (range, 1-11), and 15 (38%) patients had an intraperitoneal catheter placed for continued drainage of the rapidly accumulating ascites. Portal pressures were measured in 19 patients; 6 (15%) had moderate portal hypertension (HVPG 6-9 mm Hg), and 13 (33%) had severe portal hypertension (HVPG ≥ 10 mm Hg). Liver biopsy was performed in 24 patients. None of the patients met the criteria for classical VOD/SOS (clinical/histological) or cirrhosis (histological). The cumulative incidence of nonrelapse mortality was 63%, and the median survival duration after the development of the IRA was 7 months (range, 0.8-125.6 months). IRA is a poorly understood and often fatal complication of allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Ascite/etiologia , Ascite/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/etiologia , Hepatopatia Veno-Oclusiva/terapia , Humanos , Incidência
11.
Biol Blood Marrow Transplant ; 26(6): 1077-1083, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31786242

RESUMO

In this retrospective analysis, we evaluated the impact of age on the outcome of patients with multiple myeloma who received an autologous hematopoietic stem cell transplantation (auto-HCT) at our institution. A total of 1128 patients were divided into the older (>70 years; 182 [16%]) and the younger (≤70 years; 946 [84%]) groups. Compared with the younger cohort, older patients had a higher International Staging System (ISS) stage (ISS-II, 57 [31%] versus 215 [23%]; ISS-III, 52 [28%] versus 211 [22%]; P = .01), higher use of reduced-dose melphalan as a conditioning regimen (140 mg/m², 59 [32%] versus 29 [3%]; P < .001), and a higher comorbidity index (median, 3 versus 2; P = .01). Nonrelapse mortality at 1 year after auto-HCT was significantly higher in older patients (7 [4%] versus 9 [1%]; hazard ratio [HR], 4.1; P = .005). Complete remission rates after auto-HCT for the older and the younger groups were 41% and 46%, respectively. With a median follow-up of 52 months, the 5-year progression-free survival (PFS) was 24% (95% confidence interval [CI], 17% to 32%) and 37% (95% CI, 33% to 40%) in the older and younger groups, respectively (HR, 1.3; P = .02). Five-year OS for the older and younger groups was 56% (95% CI, 47% to 64%) and 73% (95% CI, 70% to 76%; P < .001), respectively. Older age emerged as one of the predictors of shorter OS but not PFS in the multivariate classification and regression tree analysis. In conclusion, age ≥70 years was associated with shorter PFS and OS in patients with multiple myeloma who underwent an auto-HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Idoso , Intervalo Livre de Doença , Humanos , Mieloma Múltiplo/terapia , Prognóstico , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do Tratamento
12.
Biol Blood Marrow Transplant ; 26(4): 665-671, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31881283

RESUMO

The gain/amplification CKS1B gene at chromosome region 1q21 (1q+) is one of the most common genetic aberrations in multiple myeloma (MM). Amplification of CKS1B is frequently associated with the deletion of the CDKN2C gene at chromosome region 1p32 (1p-), which is also associated with inferior outcomes. In this retrospective study, we evaluated the outcomes of patients with 1q+ and/or 1p- after high-dose therapy and autologous hematopoietic cell transplantation (auto-HCT). From January 2006 to December 2015, 1491 newly diagnosed patients with MM underwent upfront high-dose therapy and auto-HCT at our institution. Of those, 899 had the fluorescent in situ hybridization (FISH) data available. FISH was performed at diagnosis and before the start of induction in 686 (76%) patients and after the initiation of induction therapy in 213 (24%) patients. We identified 100 patients with 1q+ and/or 1p- by FISH from the cohort of 899 patients. A control group (n = 287) with diploid cytogenetics and normal FISH panel was selected from the same cohort. From the above 2 cohorts, using a propensity score matched analysis, we identified matched controls for 85 of the 100 patients with 1q+/1p-. Patients were matched for age at auto-HCT, sex, International Staging System stage, induction regimen, creatinine level, disease status at auto-HCT, conditioning regimen, and maintenance therapy. Sixty-seven (79%), 4 (5%), and 14 (16%) patients had 1q+, 1p-, or both 1q+ and 1p-, respectively. There was no significant difference in induction therapy, preparative regimen, or maintenance therapy between the 1q+/1p- and the control group. The median follow-up time for all patients was 29.2 months (range, 0.29 to 84.96). The cumulative incidence of 100-day nonrelapse mortality was 1.2% and 0% for the 1q+/1p- and the control group, respectively. Forty-two patients (50%) in the 1q+/1p- group achieved complete response compared with 40 patients (47%) in the control group. The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 79% for the 1q+/1p- group and 56% and 86% for the control group. Patients in the 1q+/1p- group were at significantly increased risk of progression or death compared to the control group (hazard ratio [HR], 2.21; confidence interval [CI], 1.18 to 4.16; P = .014). No significant association between OS in the 2 groups was observed. The outcome of the 1q+/1p- alone (with no additional high-risk cytogenetics) and the propensity score matched control groups was also compared. Median PFS for the 1q+/1p- alone subgroup was 26.6 months, compared with 38.8 months for the control group (HR, 1.9; CI, 0.9 to 4.08; P = .09). The median OS had not been reached for the 1q+/1p- alone subgroup and was 81.1 months for the control group (HR, 1.25; CI, 0.3 to 4.6; P= .73). 1q+/1p- abnormalities with amplification of CKS1B and deletion ofCDKN2Cgenes were associated with shorter PFS compared with a propensity score matched group of patients with diploid cytogenetics and normal a FISH panel. The outcomes of 1q+/1p- patients with MM have improved with the use of more effective induction, conditioning, and maintenance therapy compared with historical controls, but we still need more effective therapeutic approaches to fully overcome the negative impact of 1q+/1p-.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Cromossomos , Humanos , Hibridização in Situ Fluorescente , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Pontuação de Propensão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
13.
Clin Cancer Res ; 25(22): 6781-6787, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31481508

RESUMO

PURPOSE: Patients with multiple myeloma with t(11;14) have been considered to have standard-risk disease. However, several recent reports have shown contradictory results. We identified 95 patients with multiple myeloma with t(11;14) on FISH studies, who underwent upfront autologous hematopoietic stem cell transplant (auto-HCT) at our center. We compared their outcome with a group of standard-risk patients with multiple myeloma who had diploid cytogenetics by both conventional cytogenetics (CC) and FISH (n = 287). EXPERIMENTAL DESIGN: To reduce the bias between the groups, we performed a 1:1 propensity score matching technique for analysis. A total of 160 patients, 80 in each group, were identified. Patients in the 2 groups were matched for age, International staging system stage at diagnosis, serum creatinine at presentation, disease status at auto-HCT, type of preparative regimens, dose of melphalan used for conditioning, and induction and maintenance regimens. RESULTS: Patients in t(11;14) group had a post auto-HCT overall response rate (ORR) of 97.5% (78/80), compared with 100% (80/80) in the standard-risk control group (P = 0.50). Complete response rate in the t(11;14) group was 35% (28/80), compared with 45% (36/80) in the standard-risk control group (P = 0.26). The 4-year PFS rates were 40.8% (95% CI, 29.6%-56.1%) and 51.1% (95% CI, 39.4%-66.3%) in the t(11;14) and standard-risk control groups, respectively (P = 0.14). The 4-year OS rates were 74.9% (95% CI, 63.3%-88.7%) and 88.3% (95% CI, 80.4%-97.0%) in the t(11;14) and standard-risk control groups, respectively (P = 0.17). Also, patients with t(11;14) with concurrent cytogenetics had significantly poor PFS and OS compared with a propensity matched standard-risk control group. CONCLUSIONS: Our study confirms that t(11;14) multiple myeloma undergoing upfront autologous transplantation had similar outcomes as patients with multiple myeloma with normal cytogenetic and FISH studies. Existence of additional genomic aberrations by CC or FISH was associated with a worse outcome.


Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 14 , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Translocação Genética , Idoso , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
14.
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
15.
Biol Blood Marrow Transplant ; 25(7): 1340-1346, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30763728

RESUMO

We analyzed 186 patients with lymphoma who underwent allogeneic stem cell transplantation (ASCT) with fludarabine-melphalan (FM) conditioning and different types of donors (25 haploidentical [HD], 98 matched unrelated [MUD], and 63 matched related [MRD]) at our institution between September 2009 and January 2018. Patients received fludarabine 160 mg/m2 (40 mg/m2/day for 4 days) in combination with 1 dose of melphalan 140 mg/m2 (FM140) or 100 mg/m2 (FM100). Engraftment was similar among the 3 groups (92%, 89%, and 98%, respectively; P = .7). The 6-month cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 4% in the HD group, 14% in the MUD group, and 8% in the MRD group (P not significant), and the respective 3-year cumulative incidence of chronic GVHD was 5%, 16%, and 26% (P not significant). The respective 3-year nonrelapse mortality and relapse rates were 31%, 32%, and 10% (HD versus MUD, P = .9; HD versus MRD, P = .02) and 15%, 21%, and 39% (HD versus MUD, P = .4; HD versus MRD, P = .04). At 3 years, progression-free survival (PFS) was 59%, 44%, and 46% (P not significant); overall survival (OS) was 52%, 54%, and 67% (P not significant); and GVHD-free, relapse-free survival was 39%, 31%, and 24% (P not significant). No differences in the 3-year PFS (57% versus 43%; P = .3) and OS (64% versus 58%; P = .7) were seen between patients receiving FM100 and those receiving FM140. Our data demonstrate that in patients with lymphoma, ASCT with HD transplants have similar outcomes as ASCT with HLA-matched transplants, and the FM100 conditioning regimen appears to be at least as effective as the FM140 regimen.


Assuntos
Doença Enxerto-Hospedeiro , Linfoma , Melfalan/administração & dosagem , Transplante de Células-Tronco , Doadores de Tecidos , Adolescente , Adulto , Idoso , Aloenxertos , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/terapia , Humanos , Incidência , Linfoma/mortalidade , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
16.
Bone Marrow Transplant ; 54(4): 601-606, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30337700

RESUMO

Allogeneic SCT for older patients remains challenging at least in part due to graft-versus-host disease (GVHD) and higher non-relapse mortality (NRM). We conducted a prospective pilot study primarily for older patients undergoing matched unrelated donor (MUD) SCT using a reduced-intensity (RIC) melphalan-based conditioning and post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis with tacrolimus and mycophenolate mofetil. Twenty-two patients (median age 64, IQR 58, 66) underwent RIC MUD SCT for high-risk hematological malignancies including AML/MDS (73%), CML/MPD (18%), and other (10%). Two (9%) patients had early death; the rest (100%) engrafted. After a median follow-up of 17 months, 11 patients were alive and disease-free with an estimated 2-year progression-free (PFS) and overall (OS) survival of 48%. The cumulative incidences of grades 2-4 and 3-4 acute GVHD (aGVHD) at day + 100 and 2-years were 32 and 4%, and 59 and 24%, respectively. No cases of chronic GVHD (cGVHD) were noted. However, late acute GVHD was observed in 6 (27%) patients. In conclusion, RIC MUD SCT with melphalan-based conditioning and PTCy-based GVHD-based prophylaxis for older patients appears effective in controlling relapse. While cGVHD was not seen and early aGVHD appears controllable, a significant proportion developed late aGVHD responsible for higher NRM seen in these patients.


Assuntos
Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/terapia , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Condicionamento Pré-Transplante/métodos , Ciclofosfamida/farmacologia , Feminino , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/farmacologia , Projetos Piloto , Estudos Prospectivos , Tacrolimo/farmacologia , Doadores não Relacionados
17.
Blood Adv ; 2(17): 2254-2261, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30206098

RESUMO

Donor availability for allogeneic transplantation remains an important factor in determining outcomes of a successful transplant. We examined outcomes of 242 patients treated over 3 years who had a matched unrelated donor (MUD) search at our institution. One hundred sixty patients (66%) had a 10 of 10 MUD identified, and 85 (53%) proceeded to MUD transplantation. White patients and those with common haplotypes were more likely to have a MUD identified (odds ratio [OR], 7.4 [P < .0001]; OR, 41.6 [P < .0001]), and were more likely to proceed to transplantation with a MUD (OR, 11.2 [P < .0001]; OR, 85.1 [P = .002]). In addition, patients who were newly diagnosed/in remission at the time of MUD search had a higher probability of receiving a transplant (OR, 2.01 [P = .013]) and better progression-free survival (PFS; P < .0001). In multivariate analysis for patients who received a transplant, donor type did not influence PFS at 3 years, which was 40% for MUD and 57% for haploidentical transplants, respectively (hazard ratio, 1.2 [P = .50]). In conclusion, race, haplotype frequency, and disease status at the time of MUD search influence the probability of identifying a MUD and receiving a transplant. Patients with a low likelihood of receiving a MUD transplant may proceed to a haploidentical transplant as soon as indicated, as this approach does not appear to compromise transplant outcomes.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Teste de Histocompatibilidade , Doadores não Relacionados/provisão & distribuição , Adolescente , Adulto , Idoso , Criança , Haplótipos , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Fatores de Risco , Análise de Sobrevida , Transplante Haploidêntico , Transplante Homólogo , Adulto Jovem
20.
Clin Cancer Res ; 24(10): 2304-2311, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29476021

RESUMO

Purpose: We evaluated the effect on long-term survival of adding rituximab (R) to BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning with or without yttrium-90 ibritumomab tiuxetan (90YIT) in patients with relapsed diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplant (ASCT).Experimental design: Patients were enrolled on three consecutive phase II clinical trials. Patients received two doses of rituximab (375 and 1,000 mg/m2) during mobilization of stem cells, followed by 1,000 mg/m2 on days +1 and +8 after ASCT with R-BEAM or 90YIT-R-BEAM (90YIT dose of 0.4 mCi/kg) conditioning.Results: One hundred thirteen patients were enrolled, with 73 receiving R-BEAM and 40 receiving 90YIT-R-BEAM. All patients had a prior exposure to rituximab. The median follow-up intervals for survivors were 11.8, 8.1, and 4.2 years in the three trials, respectively. The 5-year disease-free survival (DFS) rates were 62% for R-BEAM and 65% for 90YIT-R-BEAM (P = 0.82). The 5-year overall survival rates were 73% and 77%, respectively (P = 0.65). In patients with de novo DLBCL, survival outcomes of the germinal center/activated b-cell histologic subtypes were similar with 5-year OS rates (P = 0.52) and DFS rates (P = 0.64), irrespective of their time of relapse (<1 vs. >1 year) after initial induction chemotherapy (P = 0.97).Conclusions: Administering ASCT with rituximab during stem cell collection and immediately after transplantation induces long-term disease remission and abolishes the negative prognostic impact of cell-of-origin in patients with relapsed DLBCL. The addition of 90YIT does not confer a further survival benefit. Clin Cancer Res; 24(10); 2304-11. ©2018 AACR.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B/terapia , Rituximab/uso terapêutico , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autoenxertos , Biomarcadores Tumorais , Carmustina/uso terapêutico , Causas de Morte , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Citarabina/uso terapêutico , Intervalo Livre de Doença , Etoposídeo/uso terapêutico , Feminino , Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Retratamento , Rituximab/administração & dosagem , Resultado do Tratamento , Adulto Jovem
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