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1.
Anticancer Res ; 39(4): 1899-1906, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952731

RESUMO

BACKGROUND: A retrospective analysis was performed to investigate the survival outcomes in adult acute lymphoblastic leukemia (ALL) based on treatment received. MATERIALS AND METHODS: Data from 17,504 men and women (≥18 years of age) registered in the National Cancer Database who were diagnosed with ALL between 2004 and 2013 and had follow-up to the end of 2014, were analyzed. The primary predictor variable was treatment received, and overall survival was the outcome variable. Additional variables addressed and adjusted included gender, age, race, Charleston Comorbidity Index, level of education, income, insurance, distance traveled, facility type and diagnosing/treating facility. RESULTS: The mean age of patients was 48.8 years with a standard deviation of 19.3 years. In multivariate analysis, after adjusting for secondary predictor variables, treatment modality was a statistically significant predictor of overall survival from ALL. Relative to patients who were treated with chemotherapy only, the patients who got chemotherapy and stem cell transplant had a decreased risk of mortality by 39%. Of the 5,409 patients between the ages of 18 and 39 years i.e. adolescent and young adults (AYA), no statistically significant survival difference was found between patients treated with stem cell transplant and those not. CONCLUSION: Stem cell transplant led to improved survival for all age groups except the AYA.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Fatores Etários , Idoso , Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
3.
Cancer ; 125(2): 185-193, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30480777

RESUMO

High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are established components in the treatment of multiple myeloma; however, undergoing transplantation usually requires hematopoietic support, which poses a challenge among patients who are unwilling to receive blood products. Most transplant centers decline HDT/ASCT to these patients because of safety concerns. Here, the authors' institutional data on safety, engraftment parameters, and survival outcomes after bloodless ASCT (BL-ASCT) are examined among patients with myeloma. This retrospective case-control study included patients who underwent BL-ASCT and Transfusion-supported ASCT (TS-ASCT) at Emory University Hospital between August 2006 and August 2016. In total, 24 patients who underwent BL-ASCT and 70 who underwent TS-ASCT were included. The median time for neutrophil engraftment, platelet engraftment and the median length of hospital stay all were equivalent for both groups. There were no transplant-related cardiovascular complications or mortality in either the BL-ASCT group or the TS-ASCT group. The median progression-free survival was 36 months and 44 months in the BL-ASCT and TS-ASCT groups, respectively (P = .277), and the median OS was not reached in either group at a median follow-up of 59 months after ASCT (P = .627). There was no transplant-related mortality at the 100-day or 1-year mark in either group. BL-ASCT is safe and feasible; transplant-related mortality, cardiovascular and hematologic complications are similar to those associated with TS-ASCT. Furthermore, BL-ASCT can yield similar engraftment and survival parameters comparable to those observed with TS-ASCT.


Assuntos
Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Transplante de Células-Tronco/métodos , Adulto , Idoso , Amiloidose/mortalidade , Amiloidose/terapia , Transfusão de Sangue , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Análise de Sobrevida , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Transplante Autólogo/mortalidade , Resultado do Tratamento
4.
Transplantation ; 102(12): 1994-2001, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30211830

RESUMO

Chronic kidney disease is common in patients with multiple myeloma. Historically, individuals with end-stage renal disease and multiple myeloma did poorly with renal transplantation due to higher mortality rates from the malignancy itself or associated comorbidities. However, over the past 2 decades, there have been significant advances in the treatment of multiple myeloma with the advent of new therapeutic agents resulting in an improvement of long-term survival. As a result, more individuals with multiple myeloma are being referred for kidney transplantation, especially those with good functional capacity and minimal comorbidities. Recent literature has suggested that certain patients with multiple myeloma can successfully undergo renal transplantation after stem transplantation with consideration for maintenance therapy, although caution should be used with immunomodulating drugs due to the anecdotally reported risk of acute rejection. Therefore, having a multidisciplinary approach with the transplant team and hematology both before and after transplant is crucial in maximizing the chance of success for these individuals. This review summarizes the literature on renal transplantation in patients with multiple myeloma as well as the therapeutic advancements that have occurred which may allow certain patients to undergo successful transplantation.


Assuntos
Antineoplásicos/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Mieloma Múltiplo/terapia , Transplante de Células-Tronco , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Tomada de Decisão Clínica , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade , Seleção de Pacientes , Inibidores de Proteassoma/uso terapêutico , Medição de Risco , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Resultado do Tratamento
5.
Clin Lymphoma Myeloma Leuk ; 18(11): e493-e499, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30104177

RESUMO

INTRODUCTION: Deletion 17p (del 17p) portends a poor prognosis in myeloma, but its significance in light-chain amyloidosis is unknown. PATIENTS AND METHODS: We identified patients with light-chain amyloidosis and del 17p at diagnosis, and analyzed presenting characteristics, treatments, and clinical outcomes. All had baseline biopsy results showing amyloid and serologic and marrow studies, including standard fluorescence in-situ hybridization determinations of del 17p using commercial probes. Consensus criteria for hematologic and organ involvement, progression, and response were used. Kaplan-Meier (log rank) analyses and Cox regression analysis of baseline variables were used to identify predictors of overall and progression-free survival (PFS). Six-month landmark analyses were performed to assess the impact of treatment-related variables. RESULTS: We identified 44 patients from 7 countries with median marrow and del 17p plasma cells of 22% (range, 3%-100%) and 30% (2%-93%). Ninety-five percent had cardiac involvement, including 44% stage III. Two-thirds of the patients initially received bortezomib-based therapy. Forty-nine percent of patients experienced complete response or very good partial response, with median time to best response of 4 months (range, 1-28 months). Median overall survival and PFS were 49 and 32 months. Cardiac stage and hematologic response were the key predictors of outcomes. Patients with > 50% and ≤ 50% del 17p in clonal plasma cells had median survivals of 28 and 52 months, respectively (P = .08). In landmark analyses, only hematologic response predicted both overall survival and PFS. CONCLUSION: Cardiac stage, hematologic response, and del 17p percentage impact outcomes in these cases. Emphasis should be placed on optimizing supportive care and achieving a deep hematologic response.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Transplante de Células-Tronco/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Seguimentos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/genética , Amiloidose de Cadeia Leve de Imunoglobulina/patologia , Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
6.
Clin Lymphoma Myeloma Leuk ; 18(11): e481-e491, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30100330

RESUMO

INTRODUCTION: Optimal post-remission therapy (PRT) for intermediate risk acute myeloid leukemia remains an area of ongoing research. We aimed to retrospectively compare outcomes following autologous stem cell transplantation (autoSCT) with allogeneic SCT (alloSCT) and consolidation chemotherapy (CMT) in patients with intermediate-risk karyotype AML in first complete remission. PATIENTS AND METHODS: We compared overall survival (OS) and leukemia-free survival (LFS) using propensity score (PS)-adjusted analysis of patients receiving PRT with autoSCT, matched sibling (MSD) alloSCT, unrelated/mismatch (UD/MM) alloSCT, and CMT. We included patients diagnosed between 1984 and 2003 (period of autoSCT at our center) in CR1 following induction CMT and received at least 2 consolidative cycles. RESULTS: We identified 190 patients (62 MSD-alloSCT, 18 UD/MM-alloSCT, 30 autoSCT, and 80 CMT). Baseline characteristics were used for PS calculation and were well-balanced after weight adjustment. The median follow-up for patients surviving beyond 1 year was 8.7 years. We excluded 55 patients based on PS calculation. Adjusted multivariate hazard ratio (HR), 95% confidence interval (CI) and P-value for OS, considering CMT as reference, were: MSD-alloSCT (HR, 0.4; 95% CI, 0.2-0.8; P = .009), UD/MM-alloSCT (HR, 1.5; 95% CI, 0.6-3.9; P = .363), and autoSCT (HR, 1.2; 95% CI, 0.5-3.1; P = .666), respectively. Adjusted multivariate HR, 95% CI and P-value for LFS were MSD-alloSCT (HR, 0.3; 95% CI, 0.2-0.6; P < .001), UD/MM-alloSCT (HR, 1.1; 95% CI, 0.4-2.7; P = .854), and autoSCT (HR, 0.8; 95% CI, 0.3-2.2; P = .697), respectively. CONCLUSION: Patients with intermediate risk-karyotype acute myeloid leukemia who underwent MSD-alloSCT in first complete remission had the best outcomes. There were no survival differences between autoSCT, UD/MM-alloSCT, and CMT. Further study incorporating molecular changes and minimal residual disease status is warranted to select appropriate patients for autoSCT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Quimioterapia de Consolidação/mortalidade , Cariotipagem/métodos , Leucemia Mieloide Aguda/mortalidade , Transplante de Células-Tronco/mortalidade , Adolescente , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Pontuação de Propensão , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo , Transplante Homólogo , Adulto Jovem
7.
Clin Lymphoma Myeloma Leuk ; 18(8): 533-540, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29910180

RESUMO

BACKGROUND: High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy. PATIENTS AND METHODS: We analyzed CR patients treated in 2 phase III trials, GIMEMA-RV-MM-PI-209 and RV-MM-EMN-441, to compare HDT-ASCT with an R-Alk (lenalidomide, alkylator) regimen as consolidation, and lenalidomide (R) maintenance with no maintenance. The primary endpoints were PFS, second PFS (PFS2), and OS from consolidation and maintenance (_m). RESULTS: Overall, the data from 166 patients in CR were analyzed, 95 in the HDT-ASCT group and 71 in the R-Alk group. The CR patients who received HDT-ASCT had a better PFS (hazard ratio [HR], 0.55; P = .01), PFS2 (HR, 0.46; P = .02), and OS (HR, 0.42; P = .03) compared with patients randomized to R-Alk. The survival benefit with HDT-ASCT was confirmed among all the subgroups, according to age, International Staging System (ISS stage, cytogenetic profile, and receipt of maintenance therapy. CR patients who received lenalidomide maintenance had a better PFS_m (4 years: 54% vs. 19%; HR, 0.43; P = .02) compared with those who received no maintenance. However, no difference was observed in terms of PFS2_m (4 years: 72% vs. 58%; HR, 0.83; P = .67) and OS_m (4 years: 79% vs. 72%; HR, 0.82; P = .73) with maintenance therapy. CONCLUSION: Even in CR patients, outcomes were improved by an intensified approach with HDT-ASCT consolidation and lenalidomide-based maintenance therapy.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Lenalidomida/administração & dosagem , Mieloma Múltiplo/terapia , Transplante de Células-Tronco , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Quimioterapia de Consolidação , Feminino , Humanos , Lenalidomida/efeitos adversos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Neoplasia Residual , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Transplante Autólogo
8.
Eur J Cancer ; 94: 16-25, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29505967

RESUMO

BACKGROUND: For metastatic germ cell tumour patients with intermediate prognosis (IPGCT) according to the IGCCCG classification 5-year overall survival (OS) rates of 79% were described, but recent data suggest significant changes. PATIENTS AND METHODS: To compare the outcome of current IPGCT with former patients and to find new prognosticators a retrospective observational study was performed. Eligibility criteria were: age ≥16 years, diagnosed between 1979 and 2014. Primary end-point was the 5-year OS rate. RESULTS: This database includes 707 IPGCT: group 1 was diagnosed 1979-1996 (n = 237), and group 2 1997-2014 (n = 470). Median follow-up was 8.6 years (IQR: 14.4). Group 1 and 2 received first-line treatment with BEP (median 4 cycles; range 1-6) in 99% (group 1) and 95% (group 2), respectively. The proportion of first-line chemotherapy responders (CR and marker negative PR) was similar: 94% (group 1) and 96% (group 2), respectively (P = 0.290), but OS was superior in group 2 with a 5-year OS rate of 89% compared with 83% in group 1 (P = 0.035). In refractory disease, high-dose chemotherapy and treatment beyond second line was performed more often in group 2. A lactate dehydrogenase (LDH) cut-off value of 2 ULN (P = 0.002; HR 2.121) and alpha-fetoprotein (AFP) levels of 6200 IU/ml (P = 0.032; HR 2.155) pre-chemotherapy were independent prognosticators for OS in a multivariate analysis. CONCLUSION: Outcome of IPGCT has improved and is now closer to the good prognosis category. LDH and AFP levels represent potential markers to stratify IPGCT before treatment initiation.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Embrionárias de Células Germinativas/patologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/terapia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Risco , Transplante de Células-Tronco/métodos , Transplante de Células-Tronco/mortalidade , Adulto Jovem
9.
Trials ; 19(1): 169, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29514706

RESUMO

BACKGROUND: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance. METHODS/DESIGN: ACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively. All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression. DISCUSSION: The question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM. TRIAL REGISTRATION: ISRCTN, ISRCTN10038996 . Registered on 15 December 2016.


Assuntos
Antineoplásicos/administração & dosagem , Compostos de Boro/administração & dosagem , Glicina/análogos & derivados , Quimioterapia de Manutenção/métodos , Mieloma Múltiplo/terapia , Inibidores de Proteassoma/administração & dosagem , Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos , Antineoplásicos/efeitos adversos , Compostos de Boro/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Esquema de Medicação , Feminino , Glicina/administração & dosagem , Glicina/efeitos adversos , Humanos , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/mortalidade , Masculino , Estudos Multicêntricos como Assunto , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Neoplasia Residual , Intervalo Livre de Progressão , Inibidores de Proteassoma/efeitos adversos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Terapia de Salvação , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/mortalidade , Transplante Autólogo , Resultado do Tratamento , Reino Unido
10.
Korean J Intern Med ; 33(6): 1169-1181, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29295612

RESUMO

BACKGROUND/AIMS: Data on dexamethasone, cytarabine, and cisplatin (DHAP) as a mobilization regimen, compared to high-dose cyclophosphamide (HDC), for up-front autologous stem cell transplantation (ASCT) in non-Hodgkin's lymphoma (NHL) is limited. METHODS: Consecutive patients with aggressive NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab-CHOP who underwent chemomobilization using HDC or DHAP plus granulocyte-colony stimulating factor (G-CSF) for up-front ASCT were enrolled from three institutions between 2004 and 2014. RESULTS: Ninety-six patients (57 men) were included. Sixty-five patients (67.7%) received HDC; and 31 (32.3%), DHAP. The total CD34+ cells mobilized were significantly higher in patients receiving DHAP (16.1 vs. 6.1 × 106/kg, p = 0.001). More patients achieved successful mobilization with DHAP (CD34+ cells ≥ 5.0 × 106/kg) compared to HDC (87.1% vs. 61.5%, respectively; p = 0.011), particularly within the first two sessions of apheresis (64.5% vs. 32.3%, respectively; p = 0.003). Mobilization failure rate (CD34+ cells < 2.0 × 106/kg) was significantly higher in patients receiving HDC (20.0% vs. 3.2%, p = 0.032). On multivariate analysis, the DHAP regimen (odds ratio, 4.12; 95% confidence interval, 1.12 to 15.17) was an independent predictor of successful mobilization. During chemomobilization, patients receiving HDC experienced more episodes of febrile neutropenia compared to patients receiving DHAP (32.3% vs. 12.9%, p = 0.043). CONCLUSION: The DHAP regimen was associated with a significantly higher efficacy for stem cell mobilization and lower frequency of febrile neutropenia. Therefore, DHAP plus G-CSF is an effective for mobilization in patients with aggressive NHL who were candidates for up-front ASCT.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/terapia , Rituximab/administração & dosagem , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia Febril Induzida por Quimioterapia/etiologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Mobilização de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Rituximab/efeitos adversos , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto Jovem
11.
J Clin Oncol ; 36(4): 310-318, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29226763

RESUMO

Purpose To develop a prognostic system for transplantation-age patients with primary myelofibrosis (PMF) that integrates clinical, cytogenetic, and mutation data. Patients and Methods The study included 805 patients with PMF age ≤ 70 years recruited from multiple Italian centers and the Mayo Clinic (Rochester, MN), forming two independent learning and validation cohorts. A Cox multivariable model was used to select from among a list of 22 variables those that were predictive of overall survival (OS). Integrated clinical and genetic prognostic models with (MIPSS70-plus) or without (MIPSS70) cytogenetic information were developed. Results Multivariable analysis identified the following as significant risk factors for OS: hemoglobin < 100 g/L, leukocytes > 25 × 109/L, platelets < 100 × 109/L, circulating blasts ≥ 2%, bone marrow fibrosis grade ≥ 2, constitutional symptoms, absence of CALR type-1 mutation, presence of high-molecular risk mutation (ie, ASXL1, EZH2, SRSF2, IDH1/ 2), and presence of two or more high-molecular risk mutations. By assigning hazard ratio (HR)-weighted points to these variables, three risk categories were delineated for the MIPSS70 model; 5-year OS was 95% in low-risk, 70% in intermediate-risk, and 29% in high-risk categories, corresponding to median OS of 27.7 years (95% CI, 22 to 34 years), 7.1 years (95% CI, 6.2 to 8.1 years), and 2.3 years (95% CI, 1.9 to 2.7 years), respectively. In the MIPSS70-plus model, which included cytogenetic information, four risk categories were delineated, with 5-year OS of 91% in low-risk, 66% in intermediate-risk (HR, 3.2; 95% CI, 1.9 to 5.2), 42% in high-risk (HR, 6.4; 95% CI, 4.1 to 10.0), and 7% very high-risk categories (HR, 17.0; 95% CI, 9.8 to 29.2). Both models remained effective after inclusion of older patients in the analysis. Conclusion MIPSS70 and MIPSS70-plus provide complementary systems of risk stratification for transplantation-age patients with PMF and integrate prognostically relevant clinical, cytogenetic, and mutation data.


Assuntos
Biomarcadores Tumorais/genética , Análise Citogenética , Análise Mutacional de DNA , Técnicas de Apoio para a Decisão , Mutação , Mielofibrose Primária/genética , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Minnesota , Fenótipo , Valor Preditivo dos Testes , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/mortalidade , Mielofibrose Primária/cirurgia , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Adulto Jovem
12.
Pediatr Transplant ; 22(2)2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29239087

RESUMO

In SCT, death from transplant-related complications is the major obstacle hindering improvement of transplant outcomes, and proper supportive care is essential to reduce TRM. The transplant outcomes of 210 pediatric patients with malignant and non-malignant disorders who consecutively underwent SCT in our institution from 2000 to 2013 were analyzed. The transplant years were divided into three periods: A (2000-2004), B (2005-2008), and C (2009-2013), and an improvement in 5-year OS and a decrease in 5-year TRM were observed over these time periods; that is, OS was 61.5%, 60.3%, and 79.5% (P = .062), and TRM was 19.9%, 7.9%, and 0.0% (P < .001) in periods A, B, and C, respectively. On multivariate analysis, the prognostic factor for TRM for all patients was administration of danaparoid (HR = 0.109, 95% CI = 0.033-0.363, P < .001), and for patients with hematological malignancies in allogeneic SCT, the prognostic factors were danaparoid (HR = 0.046, 95% CI = 0.006-0.326, P = .002) and advanced disease at SCT (HR = 4.802, 95% CI = 1.734-13.30, P = .003). A reduction in TRM after SCT was observed over the time periods, and supportive care with danaparoid was found to be significantly effective in reducing TRM in SCT for children.


Assuntos
Anticoagulantes/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Dermatan Sulfato/uso terapêutico , Heparitina Sulfato/uso terapêutico , Transplante de Células-Tronco/mortalidade , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Análise de Sobrevida
14.
Biol Blood Marrow Transplant ; 24(1): 127-132, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28865972

RESUMO

The kidney is the most common organ affected by immunoglobulin light-chain (AL) amyloidosis and monoclonal immunoglobulin deposition disease (MIDD), often leading to end-stage renal disease (ESRD). High-dose melphalan and stem cell transplantation (HDM/SCT) is effective for selected patients with AL amyloidosis, with high rates of complete hematologic response and potential for improved organ dysfunction. Data on tolerability and response to HDM/SCT in patients with ESRD due to AL amyloidosis and MIDD are limited. We analyzed data on toxicity, efficacy, and hematologic and renal response of HDM/SCT in 32 patients with AL amyloidosis and 4 patients with MIDD who were dialysis-dependent for ESRD treated at Boston Medical Center between 1994 and 2016. The most common grade 3/4 nonhematologic toxicities were infections (75%), metabolic abnormalities (56%), mucositis (42%), constitutional symptoms (39%), pulmonary complications (39%), and diarrhea (28%). Treatment related mortality (defined as death within 100 days of SCT) occurred in 8% (3 of 36). A complete hematologic response was achieved in 70% of evaluable patients (19 of 27) at 1 year after HDM/SCT. In the entire cohort, median overall survival (OS) after HDM/SCT was 5.8 years; median OS was 1 year for those who did not achieve a complete hematologic response and 8 years for those who did achieve a complete hematologic response. Twelve patients (33%) underwent kidney transplantation after successful treatment with HDM/SCT at a median of 2.4 years after SCT. HDM/SCT is safe and effective in inducing hematologic complete responses and prolonging survival in patients with ESRD from AL amyloidosis and MIDD. Achievement of a durable hematologic response can make these patients possible candidates for renal transplantation.


Assuntos
Amiloidose de Cadeia Leve de Imunoglobulina/terapia , Melfalan/uso terapêutico , Diálise Renal , Transplante de Células-Tronco/métodos , Adulto , Idoso , Feminino , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/complicações , Falência Renal Crônica/terapia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/mortalidade , Resultado do Tratamento
16.
Cancer Med ; 6(12): 2766-2774, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29076254

RESUMO

Overall survival (OS) is the gold-standard end point for studies evaluating autologous stem cell transplantation (ASCT) in follicular lymphoma (FL), but assessment may be elusive due to the lengthy disease course. We analyzed the validity of two earlier end points, proposed in the setting of first-line chemo-/immunotherapy, as surrogates for OS-progression-free survival (PFS) status at 24 months (PFS24) and complete response at 30 months (CR30) post-ASCT. We also have investigated the clinical features of patients with early progression after ASCT. Data were available for 626 chemosensitive FL patients who received ASCT between 1989 and 2007. Median follow-up was 12.2 years from ASCT. In the PFS24 analysis, 153 (24%) patients progressed within 24 months and 447 were alive and progression-free at 24 months post-ASCT (26 who died without disease progressions within 24 months were excluded). Early progression was associated with shorter OS (hazard ratio [HR], 6.8; P = 0.00001). In the subgroup of patients who received an ASCT in the setting or relapse after being exposed to rituximab, the HR was 11.3 (95% CI, 3.9-30.2; P < 0.00001). In the CR30 analysis, 183 of 596 (31%) response-evaluable patients progressed/died with 30 months post-ASCT. The absence of CR30 was associated with shorter OS (HR, 7.8; P < 0.00001), including in patients with prior rituximab (HR, 8.2). PFS24 and CR30 post-ASCT are associated with poor outcomes and should be primary end points. Further research is needed to identify this population to be offered alternative treatments.


Assuntos
Linfoma Folicular/cirurgia , Transplante de Células-Tronco , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Determinação de Ponto Final , Feminino , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Espanha , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
17.
Biol Blood Marrow Transplant ; 23(12): 2184-2191, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28864138

RESUMO

Since 2000, various phase III randomized controlled trials (RCTs) have investigated the efficacy of rabbit antithymocyte globulin (ATG) in patients following allogeneic stem cell transplantation (allo-SCT). Comparisons of different ATG formulations are lacking, however. Our aim was to synthesize all published efficacy evidence to enable a comparison of all available formulations of rabbit ATG in the allo-SCT setting. We performed a systematic literature review to identify all available phase III RCT evidence. We searched the Cochrane Library, MEDLINE, MEDLINE In-Process, and the website www.ClinicalTrials.gov. In addition, a trial presented at the Annual Meeting of the American Society of Hematology 2016 was added to include the most recent evidence. We identified a total of 6 RCTs, including 2 formulations: anti-T lymphocyte globulin (ATLG; Grafalon, Neovii Biotech, Lexington, MA) and polyclonal globulin immunized with human thymocytes (Thymoglobulin [Thymo]; Genzyme-Sanofi, Cambridge, MA). The evidence was synthesized using a conventional network meta-analysis (NMA). The best treatment for preventing graft-versus-host disease (GVHD) was ATLG, which had a more favorable hazard ratio (HR) compared with standard treatment (chronic GVHD: HR, .42; 95% confidence interval [CI], .31 to .56; acute GVHD grade II-IV: HR, .54; 95% CI, .39 to .73; acute GVHD grade III-IV: HR, .50; 95% CI, .29 to .86), whereas both ATLG and Thymo were at least similarly effective in terms of transplantation-related mortality (TRM) (ATLG: HR, .90; 95% CI, .61 to 1.32; Thymo: HR, .90; 95% CI, .56 to 1.44). Thymo tended to be the better treatment option regarding overall survival (OS) (HR, .86; 95% CI, .59 to 1.26). Our NMA provides the first report of the relative efficacy of all available rabbit ATG formulations in patients undergoing allo-SCT. Until additional data from randomized head-to-head comparisons are available, based on the present analysis, ATLG seems to be the best option to prevent chronic and acute GVHD. Both formulations show similar efficacy in terms of TRM, whereas Thymo appears to be the better treatment option in terms of OS.


Assuntos
Soro Antilinfocitário/uso terapêutico , Meta-Análise em Rede , Transplante de Células-Tronco/métodos , Animais , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Coelhos , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Taxa de Sobrevida , Transplante Homólogo
18.
Blood ; 130(13): 1585-1596, 2017 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-28811306

RESUMO

Multiple candidate gene-association studies of non-HLA single-nucleotide polymorphisms (SNPs) and outcomes after blood or marrow transplant (BMT) have been conducted. We identified 70 publications reporting 45 SNPs in 36 genes significantly associated with disease-related mortality, progression-free survival, transplant-related mortality, and/or overall survival after BMT. Replication and validation of these SNP associations were performed using DISCOVeRY-BMT (Determining the Influence of Susceptibility COnveying Variants Related to one-Year mortality after BMT), a well-powered genome-wide association study consisting of 2 cohorts, totaling 2888 BMT recipients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome, and their HLA-matched unrelated donors, reported to the Center for International Blood and Marrow Transplant Research. Gene-based tests were used to assess the aggregate effect of SNPs on outcome. None of the previously reported significant SNPs replicated at P < .05 in DISCOVeRY-BMT. Validation analyses showed association with one previously reported donor SNP at P < .05 and survival; more associations would be anticipated by chance alone. No gene-based tests were significant at P < .05. Functional annotation with publicly available data shows these candidate SNPs most likely do not have biochemical function; only 13% of candidate SNPs correlate with gene expression or are predicted to impact transcription factor binding. Of these, half do not impact the candidate gene of interest; the other half correlate with expression of multiple genes. These findings emphasize the peril of pursing candidate approaches and the importance of adequately powered tests of unbiased genome-wide associations with BMT clinical outcomes given the ultimate goal of improving patient outcomes.


Assuntos
Transplante de Medula Óssea/mortalidade , Intervalo Livre de Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Transplante de Células-Tronco/mortalidade , Estudos de Validação como Assunto , Aloenxertos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
19.
J Clin Oncol ; 35(29): 3279-3289, 2017 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-28742454

RESUMO

Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myélome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta-analysis demonstrates a significant OS benefit and confirms the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM when compared with placebo or observation.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Mieloma Múltiplo/terapia , Transplante de Células-Tronco , Talidomida/análogos & derivados , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Quimioterapia Adjuvante , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Lenalidomida , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Transplante de Células-Tronco/efeitos adversos , Transplante de Células-Tronco/mortalidade , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
20.
Transpl Infect Dis ; 19(4)2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28471073

RESUMO

BACKGROUND: We conducted a retrospective single-center study to investigate the potential impact of cytomegalovirus (CMV) DNAemia on mortality in allogeneic stem cell transplant (allo-SCT) recipients. METHODS: A total of 151 consecutive patients who underwent T-cell replete allo-SCT were included in the study. Patients with CMV DNAemia were treated preemptively with antivirals upon detection of plasma CMV DNA loads >1500 IU/mL. RESULTS: At least one episode of CMV DNAemia occurred in 109 (72.2%) patients, and 67 of these patients (61.5%) required one or more courses of antiviral therapy. The cumulative incidence of 1-year overall and non-relapse mortality (NRM) was 28.5% (95% confidence interval [CI], 18.4%-39.5%) and 23.2% (95% CI 12.81%-35.4%), respectively. The occurrence of either CMV DNAemia or CMV recurrences had no apparent effect on 1-year overall mortality and NRM; nevertheless, a trend towards an increased risk of death was seen in patients with one or more episodes of CMV DNAemia requiring antiviral therapy (hazard ratio [HR], 2.10; 95% CI, 0.96-4.61; P=.06 for overall mortality, and HR, 2.36; 95% CI, 0.96-5.76; P=.06 for NRM) but not in those displaying one or more self-resolving episodes. CONCLUSION: Therefore, the data suggest that withholding preemptive antiviral therapy until the plasma CMV DNA load reaches 1500 IU/mL has no apparent detrimental effect on patient survival.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/mortalidade , Citomegalovirus/isolamento & purificação , DNA Viral/sangue , Transplante de Células-Tronco/mortalidade , Adolescente , Adulto , Idoso , Citomegalovirus/genética , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Transplante de Células-Tronco/efeitos adversos , Transplantados , Transplante Homólogo , Adulto Jovem
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