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1.
Leukemia ; 32(10): 2305, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30218008

RESUMEN

Following the publication of this article, the authors noted that the pomalidomide dose for the additional SC cohort in Fig. 1 was incorrectly listed. The correct dose for pomalidomide in the additional SC cohort should be the maximum tolerated dose of 4 mg/day, not 2 mg/day as listed in the original Fig. 1. The authors apologize for any inconvenience caused.

2.
Leukemia ; 31(12): 2695-2701, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28642620

RESUMEN

This phase 1 dose-escalation study evaluated pomalidomide, bortezomib (subcutaneous (SC) or intravenous (IV)) and low-dose dexamethasone (LoDEX) in lenalidomide-refractory and proteasome inhibitor-exposed relapsed or relapsed and refractory multiple myeloma (RRMM). In 21-day cycles, patients received pomalidomide (1-4 mg days 1-14), bortezomib (1-1.3 mg/m2 days 1, 4, 8 and 11 for cycles 1-8; days 1 and 8 for cycle ⩾9) and LoDEX. Primary endpoint was to determine the maximum tolerated dose (MTD). Thirty-four patients enrolled: 12 during escalation, 10 in the MTD IV bortezomib cohort and 12 in the MTD SC bortezomib cohort. Patients received a median of 2 prior lines of therapy; 97% bortezomib exposed. With no dose-limiting toxicities, MTD was defined as the maximum planned dose: pomalidomide 4 mg, bortezomib 1.3 mg/m2 and LoDEX. All patients discontinued treatment by data cutoff (2 April 2015). The most common grade 3/4 treatment-emergent adverse events were neutropenia (44%) and thrombocytopenia (26%), which occurred more frequently with IV than SC bortezomib. No grade 3/4 peripheral neuropathy or deep vein thrombosis was reported. Overall response rate was 65%. Median duration of response was 7.4 months. Pomalidomide, bortezomib and LoDEX was well tolerated and effective in lenalidomide-refractory and bortezomib-exposed patients with RRMM.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores , Bortezomib/administración & dosificación , Dexametasona/administración & dosificación , Resistencia a Antineoplásicos , Femenino , Humanos , Lenalidomida , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Estadificación de Neoplasias , Inhibidores de Proteasoma/administración & dosificación , Inhibidores de Proteasoma/uso terapéutico , Retratamiento , Talidomida/administración & dosificación , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Resultado del Tratamiento
3.
Clin Pharmacol Ther ; 102(3): 511-519, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28160288

RESUMEN

High-dose melphalan followed by autologous stem cell transplantation remains the standard of care for eligible patients with multiple myeloma, but disease response and toxicity, including severe mucositis, varies among patients. Our randomized trial investigated duration of cryotherapy (2 and 6 h) for reduction of mucositis prevalence and severity and explored factors associated with variability in pharmacokinetics and outcomes from melphalan therapy. The results demonstrate that 2-h is at least as effective as 6-h cryotherapy in decreasing severe mucositis. From a population pharmacokinetic model, we identified that fat-free mass, hematocrit, and creatinine clearance were significant covariates, as reported previously. Furthermore, we observed the rs4240803 SLC7A5 polymorphism was significantly associated with pharmacokinetic variability, and pharmacokinetics was associated with both mucositis and neutropenia. However, melphalan exposure was not associated with progression-free or overall survival in our dataset. These findings contribute to ongoing efforts to personalize melphalan dosing in transplant patients.


Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Crioterapia/métodos , Melfalán/administración & dosificación , Mieloma Múltiple/terapia , Estomatitis/prevención & control , Adulto , Anciano , Antineoplásicos Alquilantes/efectos adversos , Antineoplásicos Alquilantes/farmacocinética , Terapia Combinada , Creatinina/metabolismo , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Transportador de Aminoácidos Neutros Grandes 1/genética , Masculino , Melfalán/efectos adversos , Melfalán/farmacocinética , Persona de Mediana Edad , Polimorfismo Genético , Estomatitis/inducido químicamente , Tasa de Supervivencia , Factores de Tiempo
4.
Bone Marrow Transplant ; 49(10): 1323-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25068419

RESUMEN

Patients who undergo autologous stem cell transplant (ASCT) for hematologic malignancies frequently have multiple comorbidities. The hematopoietic cell transplantation comorbidity index (HCT-CI), a transplant-specific modification of the Charlson comorbidity index, can predict risk of readmission following allogeneic stem cell transplant. Its utility in the autologous setting is unknown. We evaluated 620 patients who underwent ASCT at the Ohio State University from 2007 to 2012 for lymphoma or multiple myeloma (MM) to identify factors associated with readmission. Univariable and multivariable logistic regression were used to estimate the odds of readmission within 30 days of discharge following ASCT. A Cox proportional hazards model was used to evaluate OS. Sixty-four patients were readmitted within 30 days; the most common indications were fever and prolonged gastrointestinal toxicity. MM compared with lymphoma (odds ratio (OR) 1.89, 95% confidence interval (95% CI): 1.06-3.38, P=0.03), HCT-CI⩾3 (OR 1.74, 95% CI: 1.03-2.96, P=0.04) and length of hospitalization ⩾28 days (OR 3.14, 95% CI: 1.26-7.83, P=0.01) remained significantly associated with 30-day readmission in a multivariable model. While the model had excellent fit (P>0.75), its ability to predict individual patients who would be readmitted was less than acceptable (receiver-operator curve=0.64, 95% CI: 0.57-0.71). In a multivariable proportional hazards model, 30-day readmission (hazards ratio (HR) 1.81, 95% CI: 1.04-3.18, P=0.04), length of hospitalization ⩾28 days (HR 4.93, 95% CI: 2.65-9.18, P<0.001) and chemorefractory disease (HR 3.08, 95% CI: 1.74-5.43, P<0.001) were independently associated with inferior OS, but HCT-CI was not. Evaluation of other assessment tools may allow better prediction of outcomes following ASCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/mortalidad , Linfoma/mortalidad , Mieloma Múltiple/mortalidad , Acondicionamiento Pretrasplante/mortalidad , Adolescente , Adulto , Anciano , Comorbilidad , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Linfoma/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/terapia , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/métodos , Adulto Joven
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