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1.
J Clin Apher ; 33(3): 303-309, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29134688

RESUMO

BACKGROUND: Peripheral blood progenitor cell (PBPC) mobilization with chemotherapy in addition to Granulocyte-Colony Stimulating Factor (G-CSF) improves cell collection compared to G-CSF alone; however, it is associated with increased risk of neutropenic fever (NF). METHODS: We analyzed risk factors for post-priming NF and NF association with autologous stem cell transplant outcomes. Between 1998 and 2008, 593 adult patients with lymphoma underwent PBPC mobilization with etoposide and G-CSF. RESULTS: Median age was 51 years (range 18-77) and 372 (63%) were male. Diagnoses were 457 (77%) non-Hodgkin lymphoma and 136 (23%) Hodgkin lymphoma. Of 554 (93%) transplanted patients, majority were in complete or partial remission at time of transplant (88%). Overall, 141 (24%) patients were hospitalized for NF. Nine patients (6%) had bacteremia, 4 (3%) had pneumonia, 2 (<1%) had herpes simplex viral infections, and the remaining 126 (90%) had no identified infection source. NF patients had lower likelihood of proceeding to transplant (86% vs. 96%, P < .001), lower CD34+ cell dose collection (median 7.23 × 106 CD34+ cells/kg vs. 8.98 × 106 CD34+ cells/kg, P = .002), and were more likely to require > 4 days of apheresis (48% vs. 37%, P < .001). NF was associated with a higher 30-day readmission rate following transplant hospitalization (17% vs. 9%, P = .012). CONCLUSION: NF during etoposide priming is associated with lower likelihood of proceeding to transplant, lower CD34+ cell dose collection, more apheresis days required for collection and a higher 30-day readmission rate following transplant discharge.


Assuntos
Antígenos CD34/análise , Remoção de Componentes Sanguíneos , Neutropenia Febril , Mobilização de Células-Tronco Hematopoéticas/métodos , Células-Tronco de Sangue Periférico/efeitos dos fármacos , Adolescente , Adulto , Idoso , Etoposídeo/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma/terapia , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Fatores de Tempo , Transplante Autólogo , Adulto Jovem
2.
Biol Blood Marrow Transplant ; 23(5): 776-781, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28108271

RESUMO

Allogeneic hematopoietic cell transplantation conditioning regimen intensity has varied for patients with acute myeloid leukemia and myelodysplastic syndrome. A comparative effectiveness analysis was performed to assess outcomes of busulfan and fludarabine (BuFlu) versus those of fludarabine and 400 cGy total body irradiation (FluTBI) conditioning. Thirty-three subjects received BuFlu and 38 received FluTBI. The BuFlu group received more red blood cell transfusions (P = .02) and had a longer time to platelet recovery (P = .004). There were no differences between the regimens regarding incidence of acute or chronic graft-versus-host disease (GVHD), quality of life, or 2-year outcome estimates for relapse (48; 95% confidence interval [CI], 30 to 64 and 50; 95% CI, 33 to 65), nonrelapse mortality (29; 95% CI, 14 to 45 and 29; 95% CI, 15 to 44), relapse-free survival (27; 95% CI, 13 to 43 and 29; 95% CI, 16 to 44), and overall survival (35; 95% CI, 19 to 51; and 37; 95% CI, 22 to 52), respectively. These comparable outcomes have implications for health care resource utilization. Future prospective investigation comparing these regimens with larger patient cohorts and additional strategies to prevent relapse and limit toxicities as well as cost-effectiveness analyses are warranted.


Assuntos
Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Bussulfano/uso terapêutico , Transfusão de Eritrócitos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Qualidade de Vida , Recidiva , Análise de Sobrevida , Condicionamento Pré-Transplante/normas , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Irradiação Corporal Total/métodos
3.
Biol Blood Marrow Transplant ; 22(9): 1588-1595, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27343718

RESUMO

High-dose busulfan (Bu) is an integral component of commonly used preparative regimens for both allogeneic and autologous transplantation. There is significant interest in comparing the efficacy and toxicity of administering Bu every 6 (Bu6) or every 24 hours (daily Bu). To facilitate a therapeutic dose-monitoring protocol, we transitioned from Bu6 to daily Bu dosing for patients with Hodgkin and non-Hodgkin lymphoma undergoing autologous stem cell transplantation (ASCT). Here, we retrospectively review outcomes of 400 consecutive eligible lymphoma patients who underwent ASCT from 2007 to 2013 with high-dose busulfan (Bu), cyclophosphamide (Cy), and etoposide (E). Bu was given at a fixed dose of either .8 mg/kg every 6 hours for 14 doses for 307 patients or a fixed dose of 2.8 mg/kg every 24 hours for 4 doses (days -9 through -6) for 93 patients who underwent transplantation after the transition from Bu6 to daily Bu was made. Toxicity was assessed using pulmonary and liver function tests (LFT) at specified time points before and after ASCT. Baseline patient and disease characteristics of patients dosed with Bu6 and daily Bu were similar. There was no significant difference in forced expiratory volume in 1 second or diffusing capacity of the lungs for carbon monoxide before and after transplantation in the Bu6 versus daily Bu cohorts. Changes in LFTs with daily Bu were not significantly different than those with Bu6. There were no differences in relapse, nonrelapse mortality, progression-free survival, or overall survival between Bu6 and Bu 24 administration schedules in univariable or multivariable analysis (P ≥ .34). For a subset of 23 patients who had first-dose Bu levels measured, we observed significant variation in an median estimated cumulative area under the curve (AUC) of 17,568 µM-minute (range, 12,104 µM-23,084 µM-minute). In conclusion, daily Bu with Cy/E is more convenient than Bu6, has equivalent outcomes, and results in no increase in either hepatic or pulmonary toxicity. Consistent with previous reports, there is a significant range of Bu AUC levels, with a standard deviation of 13%. These data provide rationale for our prospective clinical trial of real-time therapeutic dose monitoring of Bu.


Assuntos
Bussulfano/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/tratamento farmacológico , Adulto , Idoso , Bussulfano/farmacocinética , Bussulfano/uso terapêutico , Bussulfano/toxicidade , Ciclofosfamida/uso terapêutico , Esquema de Medicação , Etoposídeo/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Doença de Hodgkin/complicações , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Testes de Função Hepática , Linfoma/complicações , Linfoma/mortalidade , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
4.
Am J Hematol ; 89(4): 349-54, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24273135

RESUMO

A previous interim report of MM-011, the first study that combined lenalidomide with anthracycline-based chemotherapy followed by lenalidomide maintenance for relapsed and/or refractory multiple myeloma (RRMM), showed promising safety and activity. We report the long-term outcomes of all 76 treated patients with follow-up ≥ 5 years. This single-center phase I/II study administered lenalidomide (10 mg on days 1-21 of every 28-day cycle), intravenous liposomal doxorubicin (40 mg/m(2) on day 1), dexamethasone (40 mg on days 1-4), and intravenous vincristine (2 mg on day 1). After 4-6 planned induction cycles, lenalidomide maintenance therapy was given at the last tolerated dose until progression, with or without 50 mg prednisone every other day. The median number of previous therapies was 3 (range, 1-7); 49 (64.5%) patients had refractory disease. Forty-three (56.6%) patients received maintenance therapy. Grade 3/4 adverse events occurred during induction and maintenance therapy in 48.7% and 25.6% of patients, respectively. Four (5.3%) treatment-related deaths occurred during induction. Responses were seen in 53.0% (at least partial response) and 71.2% (at least minor response) of patients. Overall, median progression-free survival and overall survival were 10.5 and 19.0 months, respectively; in patients with refractory disease these values were 7.5 and 11.3 months, respectively. Lenalidomide with anthracycline-based chemotherapy followed by maintenance lenalidomide provided durable control in patients with RRMM (ClinicalTrials.gov number, NCT00091624).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Doenças Hematológicas/induzido quimicamente , Humanos , Controle de Infecções , Estimativa de Kaplan-Meier , Cariotipagem , Lenalidomida , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Modelos de Riscos Proporcionais , Indução de Remissão , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/análogos & derivados , Trombose/prevenção & controle , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos
5.
Biol Blood Marrow Transplant ; 18(6): 874-80, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22040844

RESUMO

Patient readmission within 30 days from discharge has been perceived by the Centers for Medicare and Medical Services as an indicator of poor healthcare quality for specific high-cost medical conditions. Patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are often being readmitted. Our study identified the risk factors for 30-day readmission among 618 adult recipients of myeloablative allo-HCT from 1990 to 2009. Two hundred forty-two (39%) of 618 patients (median age = 42 years [range: 18-66]) were readmitted a median of 10 days (range: 1-30) from their hospital discharge. Median duration of readmission was 8 days (range: 0-103). Infections (n = 68), fever with or without identified source of infection (n = 63), gastrointestinal complications (n = 44), graft-versus-host disease (GVHD) (n = 38), and other reasons (n = 29) accounted for 28%, 26%, 18%, 16%, and 12% of readmissions, respectively. During their index admission, patients who were subsequently readmitted had more documented infections (P < .001), higher hematopoietic cell transplantation comorbidity index (HCT-CI) (P < .01), total body irridiation (TBI)-based conditioning (P < .001), unrelated donor (P < .001), and peripheral stem cell (P = .014) transplantation. In multivariable analysis, HCT-CI (odds ratio [OR] = 1.78; 95% confidence interval [CI], 1.25-2.52), TBI-based preparative regimen (OR = 2.63; 95% CI, 1.67-4.13), and infection during admission for allo-HSCT (OR = 2.00; 95% CI, 1.37-2.92) predicted 30-day readmission. Thirty-day readmission itself was an independent predictor of all-cause mortality (hazard ratio [HR](Adj) = 1.66; 95% CI, 1.36-2.10). Our data emphasize the importance of a risk-standardized approach to 30-day hospital readmission if it is used as a quality-of-care metric for bone marrow transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Linfoide/terapia , Leucemia Mieloide/terapia , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Tempo de Internação/estatística & dados numéricos , Leucemia Linfoide/imunologia , Leucemia Linfoide/mortalidade , Leucemia Mieloide/imunologia , Leucemia Mieloide/mortalidade , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Readmissão do Paciente/estatística & dados numéricos , Qualidade da Assistência à Saúde , Recidiva , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Irradiação Corporal Total
6.
Biol Blood Marrow Transplant ; 17(7): 1079-83, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21193053

RESUMO

Vitamin D (VD) deficiency can cause osteomalacia, bone pain, muscle weakness, fatigue, and increased risk of fracture, and may precipitate or exacerbate osteopenia and osteoporosis. Patients receiving treatment for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) may have limited exposure to sunlight and often experience gastrointestinal side effects that may decrease their ability to maintain an adequate VD level. We hypothesized that patients with AML and ALL would have a low VD level after allogeneic hematopoietic cell transplant (HCT), and that these patients would have a high incidence of osteoporosis/osteopenia. We therefore studied the incidence of low VD level and low bone mineral density after HCT. Of 289 patients with AML or ALL undergoing HCT between January 1, 2000, and January 31, 2009, at the Cleveland Clinic, 58 (20.1%) patients had VD testing after HCT. Of these, 52 (89.7%) patients had a low VD level, and 6 (10.3%) had a normal level. Most patients with VD testing had graft-versus-host disease (GVHD) and were taking corticosteroids (94.8% and 98.3%, respectively). Of the 49 patients with VD testing who also had bone mineral density testing, 65% had abnormal (low bone density) results. Only 21% of patients with VD testing were taking VD supplements prior to testing, and 65% had an elevated parathyroid hormone level. We found that most patients did not have VD testing after HCT, but those that did were very likely to have a low level and have low bone mineral density. Those with a low VD level were likely to have received corticosteroids, have GVHD, and have an elevated parathyroid hormone (PTH) level. Given the potential morbidity of low VD level, VD deficiency should be considered after HCT. Prospective study of VD level and its impact on morbidity and mortality after HCT is warranted.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/sangue , Complicações Pós-Operatórias/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Deficiência de Vitamina D/etiologia , Vitamina D/sangue , Adolescente , Corticosteroides/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Idoso , Densidade Óssea , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/etiologia , Suplementos Nutricionais , Feminino , Gastroenteropatias/complicações , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Incidência , Tempo de Internação , Leucemia Mieloide Aguda/cirurgia , Masculino , Desnutrição/complicações , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/etiologia , Hormônio Paratireóideo/sangue , Complicações Pós-Operatórias/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Homólogo , Vitamina D/administração & dosagem , Deficiência de Vitamina D/epidemiologia , Adulto Jovem
7.
Br J Haematol ; 153(3): 358-63, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21410449

RESUMO

Prior series have demonstrated that early relapsed (within 1 year) or refractory Hodgkin lymphoma (HL) is associated with poor prognosis. To determine the outcome for patients with early relapsed/refractory HL in the modern era, we combined data from two large transplant centres, Cleveland Clinic Taussig Cancer Institute (CCTCI) and Memorial Sloan-Kettering Cancer Center (MSKCC), and analysed consecutive patients transplanted for relapsed/refractory HL following induction failure or remission durations of <1 year. Two hundred and fourteen patients were analysed and the event-free survival (EFS) and overall survival (OS) at 6 years for all patients were 45% and 55%, respectively. Factors significant for prognosis in multivariate analysis were extranodal disease and bulky disease (≥5 cm). Patients with 0, 1, or 2 risk factors achieved 6 year EFS of 65%, 47%, and 24% and 6 year OS of 81%, 55%, and 27%, respectively. Patients with the sole risk factor of early relapsed/refractory disease achieved good outcomes in this large series; however the presence of bulk and/or extranodal disease significantly reduced EFS and OS. Patients with these additional risk factors are best suited for clinical trials investigating novel salvage regimens and post-transplant maintenance strategies.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Métodos Epidemiológicos , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Resultado do Tratamento , Vimblastina/uso terapêutico , Adulto Jovem
8.
Br J Haematol ; 152(5): 561-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21223255

RESUMO

High dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the preferred treatment modality for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). To assess long-term outcomes of these patients, we retrospectively analysed data from 309 consecutive patients who underwent ASCT for DLBCL between 1994 and 2006. We found that non-relapse mortality (NRM) became the major cause of death beginning approximately 8 years after ASCT. The most common causes of NRM during the study period were respiratory failure (31%), infection (13%), cardiac toxicity (15%) and secondary malignancy (15%). The strongest predictor of relapse mortality (RM) was disease status at transplant: patients who were in second or greater complete or partial remission had a higher risk of RM than those in first complete or partial remission [hazard ratio (HR) 3·7, P<0·001], as did those who were relapsed or refractory (HR 4·9, P<0·001). We describe the longest reported follow-up of a large cohort of DLBCL patients uniformly-treated with ASCT. Although relapse was initially the more likely cause of death, NRM exceeded RM after 8 years. After ASCT, surviving patients have significantly increased risk mortality rates relative to the general population and this excess risk persists over time.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Métodos Epidemiológicos , Feminino , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
9.
J Clin Apher ; 26(3): 111-5, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21647951

RESUMO

Early and reliable prediction of the likelihood of achieving adequate stem cell collection for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) would improve collection efficiency, prevent unnecessary aphereses, and permit appropriate treatment alterations. No previous study has reported a threshold CD34+ cell collection quantity on Day 1 or 2 of leukapheresis that could predict successful stem cell collection. We performed a retrospective analysis of all MM patients undergoing first attempt of stem cell collection at our institution from 2001 through 2008. Recursive partitioning analysis was used to identify Day 1 or Day 1+2 CD34+ collection quantity that predicted failure to reach target ≥ 2 × 10(6) CD34+ cells/kg within five days of collection. Totally, 172 patients were included in the analysis. Patients underwent mobilization with G-CSF or G-CSF+ chemotherapy. 23 of 172 patients (13.4%) failed to collect sufficient (≥ 2 × 10(6) CD34+ cells/kg) CD34+ cells after five days of apheresis: 22 of 29 who collected ≤ 0.70 × 10(6) CD34+ cells/kg and 1 of 143 who collected > 0.70 × 10(6) CD34+ cells/kg (75.9% vs. 0.7%, P < 0.001) on Day 1. Collection failure occurred in 23 of 30 patients who collected ≤ 1.54 × 10(6) CD34+ cells/kg and 0 of 142 who collected >1.54 × 10(6) CD34+ cells/kg (76.7% vs. 0%, P < 0.001) on Days 1 + 2. Day 1 CD34+ cell collection quantity identifies patients unlikely to achieve adequate collection for ASCT. Patients who collect ≤ 0.70 × 10(6) CD34+ cells/kg on day 1 could be considered for treatment modifications to improve CD34+ collection, such as early administration of plerixafor or large volume apheresis.


Assuntos
Antígenos CD34/análise , Mobilização de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Valor Preditivo dos Testes , Adulto , Idoso , Contagem de Células Sanguíneas , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/normas , Humanos , Leucaférese/métodos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Fatores de Tempo , Transplante Autólogo , Falha de Tratamento
10.
Biol Blood Marrow Transplant ; 16(12): 1738-46, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20558313

RESUMO

Allogeneic hematopoietic stem cell transplantation (SCT) for patients who have previously undergone allogeneic or autologous SCT is potentially curative, but dangerous. To identify patient, disease, and treatment characteristics associated with outcome, we analyzed prognostic factors in 98 consecutive patients who underwent second transplants using allogeneic donors at the Cleveland Clinic between May 1987 and October 2008. Inclusion criteria included age ≥18 years, first SCT either autologous or allogeneic, and second SCT allogeneic. Patients whose second transplant was myeloablative (MA) had shorter survival (median 3.2 versus 14.7 months, P < .001) than patients whose second transplant was nonmyeloablative (NMA). In multivariable analysis, MA second transplant was associated with a higher risk of NRM (hazard ratio [HR] 2.01, P = 0.022) and death (HR 2.13, P = 0.002). Improved survival after NMA second transplant occurred primarily in patients without acute leukemia and when the first transplant was allogeneic. Among 17 patients transplanted within 3 months of first transplant, mortality was 100% and median survival was 2.3 months. MA transplantation within 3 months of prior SCT carries an unacceptably high rate of NRM. NMA second transplants were associated with substantially less NRM and despite a higher incidence of relapse, significantly improved survival compared to MA second transplants.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia/mortalidade , Leucemia/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Recidiva , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
11.
Br J Haematol ; 148(2): 226-34, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19821828

RESUMO

Autologous stem cell transplantation (ASCT) with cyclophosphamide, etoposide and oral busulfan (BuCyVP) is an effective therapy for relapsed or refractory non-Hodgkin lymphoma (NHL). Substituting intravenous for oral busulfan reduces variability in drug exposure, potentially improving the safety and efficacy of the BuCyVP regimen. We retrospectively compared the outcomes of 604 consecutively treated patients who underwent ASCT for NHL with BuCyVP using oral (n = 468) or IV (n = 136) busulfan, without measurement of busulfan levels for pharmacokinetic (PK) analysis. Patients who received oral busulfan experienced more severe oral mucositis and a higher incidence of nonrelapse mortality. Median overall survival (OS) after ASCT was 72 months with oral busulfan but was not reached for the IV busulfan group. IV busulfan was associated with a lower rate of relapse, and superior relapse-free survival (RFS) and OS. In multivariate models, the route of busulfan administration was an independent prognostic factor for relapse (P = 0.01), RFS (P = 0.002) and OS (P = 0.001). IV busulfan appears to provide better efficacy and lower toxicity than oral busulfan in ASCT with BuCyVP for NHL. Whether PK-based busulfan dosing can achieve further improvements in this setting is worthy of study.


Assuntos
Bussulfano/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma não Hodgkin/terapia , Agonistas Mieloablativos/administração & dosagem , Condicionamento Pré-Transplante/métodos , Administração Oral , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Etoposídeo/uso terapêutico , Feminino , Humanos , Injeções Intravenosas , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida , Transplante Autólogo , Adulto Jovem
12.
Clin Lymphoma Myeloma Leuk ; 18(1): e95-e102, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29208403

RESUMO

BACKGROUND: Young fit patients with mantle cell lymphoma (MCL) are commonly treated with induction chemotherapy followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT). Induction regimens with modifications of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and/or incorporation of high-dose cytarabine (HDAC) appear more effective than R-CHOP alone. PATIENTS AND METHODS: We adopted a modification of the Nordic protocol using standard, rather than higher dose R-CHOP, alternating with HDAC (rituximab plus HDAC), for 3 cycles each or, for patients already treated with R-CHOP alone before referral for AHCT, an additional 2 cycles of rituximab plus HDAC. We herein report our experience with 28 patients treated with this regimen who proceeded to AHCT, and compare their outcomes with patients treated with either standard-dose R-CHOP (n = 38) or R-HCVAD/MA (cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate, and cytarabine; n = 21), before AHCT. RESULTS: With a median follow-up duration of 26 months, our data show that this modification of the Nordic regimen is a highly effective pre-AHCT first-line therapy for MCL (3-year progression-free and overall survival rates of 69% and 75%, respectively). CONCLUSION: By using a less intense induction, this regimen can serve as a platform for combined use of novel agents, with less risk of additive toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Célula do Manto/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Feminino , Humanos , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Mayo Clin Proc ; 81(7): 889-95, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16835968

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of adding thalidomide to the pegylated liposomal doxorubicin, vincristine, and decreased-frequency dexamethasone (DVd) regimen for multiple myeloma. PATIENTS AND METHODS: Patients newly diagnosed as having active multiple myeloma and those with relapsed-refractory disease were studied between August 2001 and October 2003. Patients received DVd as previously described. Thalidomide was given at 50 mg/d orally and the dose increased slowly to a maximum of 400 mg/d. At the time of best response, patients received maintenance prednisone, 50 mg orally every other day, and daily thalidomide at the maximum tolerated dose for each patient. The primary end point was the rate of complete responses plus very good partial responses as defined by the European Group for Blood and Marrow Transplantation criteria and the Intergroupe Français du Myélome, respectively. RESULTS: Of 102 eligible patients, 53 were newly diagnosed as having multiple myeloma, and 49 had been previously treated for multiple myeloma. The complete response plus very good partial response rate was 49% and 45%, with an overall response rate of 87% and 90% for patients with newly diagnosed and previously treated multiple myeloma, respectively. Furthermore, better responses were associated with improved progression-free and overall survival. The most common grade 3 and 4 adverse events were thromboembolic events (25%), peripheral neuropathy (22%), and neutropenia (14%). CONCLUSIONS: The addition of thalidomide to the DVd regimen significantly improves the response rate and quality of responses compared with the DVd regimen alone. This improvement is associated with longer progression-free and overall survival. The rate of observed quality responses is comparable to responses seen with high-dose therapy.


Assuntos
Dexametasona/administração & dosagem , Doxorrubicina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Talidomida/uso terapêutico , Vincristina/uso terapêutico , Idoso , Antineoplásicos Fitogênicos/uso terapêutico , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/uso terapêutico , Quimioterapia Combinada , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
15.
Med Oncol ; 23(2): 263-72, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16720927

RESUMO

BACKGROUND: Single-agent arsenic trioxide has shown promising results in patients with relapsed or refractory multiple myeloma (MM). Because preclinical data suggested greater activity with dexamethasone and ascorbic acid, a phase 2 trial of the combination of arsenic trioxide, dexamethasone, and ascorbic acid in patients with relapsed or refractory MM was conducted. METHODS: Twenty patients in whom no more than two previous therapies had failed were enrolled. The mean age was 62 yr, and 55% of the patients had refractory disease. The regimen consisted of 14- or 15-wk cycles, with the first cycle considered induction, followed by one or two consolidation cycles with a reduced steroid schedule and then a maintenance cycle in responding patients. RESULTS: The overall response rate was 30%, with at least stable disease in 80% of patients. Median progression- free survival was 316 d in all patients and 584 d in those with a response. The regimen was well tolerated, with most adverse events being mild or moderate. CONCLUSIONS: This study showed the clinical efficacy and tolerability of the combination of arsenic trioxide, dexamethasone, and ascorbic acid. Further study is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/efeitos adversos , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Óxidos/administração & dosagem , Óxidos/efeitos adversos , Recidiva , Vitaminas/administração & dosagem , Vitaminas/efeitos adversos
16.
Mayo Clin Proc ; 80(12): 1568-74, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16342649

RESUMO

OBJECTIVE: To study the efficacy of daily low-dose aspirin (81 mg orally) in decreasing the incidence of venous thromboembolic events (VTEs) in patients with multiple myeloma receiving pegylated doxorubicin, vincristine, and decreased-frequency dexamethasone, plus thalidomide (DVd-T). PATIENTS AND METHODS: In this phase 2 clinical trial of DVd-T, conducted by the Cleveland Clinic Foundation from August 2001 to October 2003, 105 patients were enrolled. The first 35 patients experienced increased numbers of VTEs. von Willebrand levels and platelet aggregation to ristocetin before and after treatment with DVd-T increased significantly, suggesting a pathophysiology involving platelet-endothelial interaction. Aspirin was added to the regimen, thus generating 3 patient groups: group 1 received aspirin from the start of DVd-T treatment before the study began (58 patients), group 2 received aspirin after the start of DVd-T treatment and after the study began (26 patients), and group 3 did not receive daily low-dose aspirin during the study (19 patients). Two patients being treated with warfarin for other indications were excluded from the study. The primary end point for this study was the incidence of VTE in the form of either deep venous thrombosis or pulmonary embolism. Secondary end points were the time to the first VTE, time to the composite end point of death or first VTE, and incidence of bleeding complications. RESULTS: After a median follow-up of 24 months, on an intent-to-treat basis, 26 posttreatment VTEs occurred after a median of 90 days, with 19% occurring in group 1, 15% in group 2, and 58% in group 3. Following multivariate time-to-event analysis, aspirin use continued to be associated with lower relative risk of VTE (hazard ratio, 0.22; confidence interval, 0.10-0.47; P<.001) and of the composite end point (hazard ratio, 0.28; confidence interval, 0.15-0.51; P<.001). CONCLUSION: Daily low-dose aspirin (81 mg orally) given to patients with newly diagnosed and relapsed/refractory multiple myeloma who were receiving DVd-T reduced the incidence of VTEs without an increase in bleeding complications.


Assuntos
Aspirina/administração & dosagem , Fibrinolíticos/administração & dosagem , Imunossupressores/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Talidomida/efeitos adversos , Trombose Venosa/induzido quimicamente , Trombose Venosa/prevenção & controle , Adulto , Idoso , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Talidomida/administração & dosagem , Vincristina/administração & dosagem , Vincristina/efeitos adversos
17.
Hematol Oncol Stem Cell Ther ; 8(3): 115-24, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26183670

RESUMO

OBJECTIVE/BACKGROUND: The most common indication for high-dose chemotherapy (HDC) and autologous hematopoietic cell transplantation (AHCT) in the 1990s was breast cancer. Several randomized trials and a more recent meta-analysis failed to show a survival benefit for AHCT in metastatic breast cancer (MBC); however, they demonstrated a better-than-expected 10-year to 15-year survival in 5-15% of patients. We thus evaluated the long-term results of treatment with HDC and AHCT in MBC at our institution. METHODS: From 1984 to 2000, 285 patients underwent AHCT for MBC. The patient characteristics were collected through the Cleveland Clinic, United Transplant Database. A retrospective review of the medical records of the long-term surviving breast-cancer patients treated with HDC and AHCT was conducted. RESULTS: With a median follow-up of 169 months, 34 (12%) remain alive. Of the 251 patients who died, 218 (87%) died of metastatic disease. A comparison by age (<50 years and >50 years) and hormonal status did not demonstrate any differences in relapse (p=.33 and p=.32, respectively) or survival (p=.13 and p=.42). Of the 34 long-term survivors, sufficient data were available on 28 patients, and further evaluation revealed that the majority had a primary or locally recurrent oligometastatic disease. CONCLUSION: This retrospective evaluation of patients who underwent AHCT for MBC demonstrates long-term survival in a small subset of patients, primarily those with primary or recurrent oligometastatic disease. Oligometastatic breast cancer is a distinct entity within MBC, which may be curable with multimodality therapy. We thus conclude there remains no overall-survival benefit to HDC in MBC.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama Masculina/mortalidade , Neoplasias da Mama/mortalidade , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/terapia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Análise Multivariada , Metástase Neoplásica , Recidiva , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
J Pain Symptom Manage ; 25(3): 288-91, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12614964

RESUMO

Pruritus is a relatively rare but distressing symptom associated with cholestasis, renal failure, and malignancies. Medical management recently has included the use of ondansetron and paroxetine. We report four patients whose pruritus responded to mirtazapine.


Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Mianserina/uso terapêutico , Prurido/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Colestase/complicações , Feminino , Humanos , Masculino , Mianserina/análogos & derivados , Pessoa de Meia-Idade , Mirtazapina , Neoplasias/complicações , Prurido/etiologia , Insuficiência Renal/complicações
20.
Leuk Lymphoma ; 52(6): 986-93, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21314484

RESUMO

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone combined with cytarabine and methotrexate) is an intense chemotherapy regimen frequently used for hematologic malignancies including mantle cell lymphoma. To address whether treatment with hyper-CVAD impairs mobilization of peripheral blood stem cells, we retrospectively analyzed mobilization data from 77 consecutive adult patients with mantle cell lymphoma who underwent peripheral blood stem cell (PBSC) mobilization for planned autologous stem cell transplant (ASCT). Compared to patients treated with alternative regimens, patients treated with hyper-CVAD collected fewer CD34+ cells, required more total days of pheresis, and more frequently required a second mobilization attempt, despite being more likely to have undergone mobilization with a VP16-containing regimen. In multivariable linear regression analysis, treatment with hyper-CVAD was associated with a significant reduction in total CD34+ cells mobilized (p < 0.001). These findings suggest that alternative mobilizing strategies prior to ASCT are needed for patients with mantle cell lymphoma who have received hyper-CVAD.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Linfoma de Célula do Manto/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Adulto , Idoso , Antígenos CD34/sangue , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucaférese/métodos , Linfoma de Célula do Manto/sangue , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Vincristina/administração & dosagem
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