RESUMEN
Procalcitonin (PCT) is a a marker of bacterial infection. Its prognostic role in the critically-ill patient, however, is still object of debate. Aim of this study was to evaluate the capacity of admission PCT (aPCT) in assessing the prognosis of the critically-ill patient regardless the presence of bacterial infection. A single-cohort, single-center retrospective study was performed evaluating critically-ill patients admitted to a stepdown care unit. Age, sex, Simplified Acute Physiology Score II (SAPS-II), shock, troponin-I, aPCT, serum creatinine, cultures and clinical endpoints (in-hospital mortality or Intensive Care Unit (ICU) transfer) were collected. Time free from adverse event (TF-AE) was defined as the time between hospitalization and occurrence of one of the clinical endpoints, and calculated with Kaplan-Meier curves. We engineered a new predictive model (POCS) adopting aPCT, age and shock.We enrolled 1063 subjects: 450 reached the composite outcome of death or ICU transfer. aPCT was significantly higher in this group, where it predicted TF-AE both in septic and non-septic patients. aPCT and POCS showed a good prognostic performance in the whole sample, both in septic and non-septic patients. aPCT showed a good prognostic accuracy, adding informations on the rapidity of clinical deterioration. POCS model reached a performance similar to SAPS-II.
Asunto(s)
Biomarcadores/metabolismo , Enfermedad Crítica/mortalidad , Mortalidad Hospitalaria/tendencias , Inflamación/diagnóstico , Unidades de Cuidados Intensivos/tendencias , Puntuaciones en la Disfunción de Órganos , Polipéptido alfa Relacionado con Calcitonina/análisis , Anciano , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Inflamación/metabolismo , Masculino , Polipéptido alfa Relacionado con Calcitonina/metabolismo , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Maintenance therapy was explored in multiple myeloma (MM) patients after conventional thalidomide, dexamethasone and pegylated liposomal doxorubicin (ThaDD). Patients with newly or relapsed MM obtaining at least minor response after 6 ThaDD courses, were randomised to receive alpha-interferon (IFN) 3 MU 3 times a week or thalidomide 100 mg daily until relapse. Both groups also received pulsed dexamethasone 20 mg 4 d a month. Fifty-one patients were randomized in the IFN-dexamethasone (ID) arm and 52 in the thalidomide-dexamethasone (TD) arm. The characteristics of two groups were similar. A significantly better 2-years progression-free survival (PFS; 63% vs. 32%; P = 0.024) and overall survival (84% vs. 68%; P = 0.030) was observed in the thalidomide arm. In high-risk patients and in those achieving less than very good partial response after induction, TD fared better in term of PFS. Main side effects were peripheral neuropathy and constipation in TD group, fatigue, anorexia and haematological toxicity in ID arm. There was a 21% probability of discontinuation at 3 years in the thalidomide arm and 44% in the IFN arm (P = 0.014). Low-dose thalidomide plus pulsed low-dose dexamethasone after conventional thalidomide combination-based therapy was also feasible in the long term, enabling significantly better residual disease control if compared with a standard maintenance therapy.
Asunto(s)
Dexametasona/administración & dosificación , Inmunosupresores/uso terapéutico , Interferón-alfa/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Talidomida/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Dexametasona/uso terapéutico , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Estudios Prospectivos , Recurrencia , Inducción de Remisión , Estadísticas no Paramétricas , Tasa de Supervivencia , Talidomida/uso terapéuticoRESUMEN
BACKGROUND: Few studies have focused on factors affecting outcome in patients with multiple myeloma (MM) treated with thalidomide-based therapy. We investigated factors affecting response, progression-free survival (PFS), and overall survival (OS) in patients with MM treated with the thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) regimen with the aim to select patients benefiting more from this therapy. PATIENTS AND METHODS: Sixty-six patients with MM were treated first line with the ThaDD regimen. We analyzed demographics and disease-related characteristics to search for factors affecting response (> or = very good partial remission [VGPR] vs. < VGPR], PFS, and OS. RESULTS: Overall, 45 patients (68%) showed response > or = VGPR; median TTP and OS were 23.5 months and 35.5 months, respectively. Multivariate analysis selected only serum C-reactive protein (sCRP) as a predictive factor for response (P < .0001). By multivariate analysis, normal sCRP level (P = .001) and response to treatment > or = VGPR (P = .007) were found to be associated with longer PFS. The factors that remained significantly associated with a longer OS when assessed by multivariate analysis were normal sCRP level (P = .005) and response to therapy > or = VGPR (P = .019). CONCLUSION: Serum C-reactive protein before therapy and response after therapy are the only factors useful in identifying patients benefiting from anthracycline/thalidomide-based therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Mieloma Múltiple/sangre , Mieloma Múltiple/terapia , Anciano , Antraciclinas/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Talidomida/administración & dosificación , Resultado del TratamientoRESUMEN
OBJECTIVES: Nearly all patients with multiple myeloma (MM) relapse or become refractory to front-line therapy. Several salvage therapies have been explored, but the optimal combination regimen has not been defined. We performed a case-matched study comparing patients with relapsed/refractory MM receiving thalidomide-dexamethasone alone or the combination thalidomide-dexamethasone-liposomal pegylated doxorubicin. METHODS: Forty-seven patients received thalidomide (100 mg/d), dexamethasone (40 mg p.o. on days 1-4 and 9-12), and pegylated liposomal doxorubicin (40 mg/m(2) on day 1 every 28 d) (ThaDD). Their clinical outcome was compared with that of 47 pair mates selected from patients treated at relapse with thalidomide (100 mg/d) and dexamethasone (40 mg p.o. on days 1-4) (Thal-Dex) and matched for age, beta2-microglobulin and previous therapy. RESULTS AND CONCLUSIONS: Overall response rate was significantly higher in ThaDD group (92% vs. 63.5%; P < 0.0001) as partial response rate (> or =PR) (75.5% vs. 59.5%; P = 0.077), very good partial response rate (> or =VGPR) (36% vs. 15%; P = 0.018) and near complete remission rate (> or =nCR) (30% vs. 10.5%; P = 0.002). Non-hematologic toxicity was similar in the two groups of patients whereas hematologic toxicity and infections were significantly higher in ThaDD patients. Median progression-free survival, event-free survival, and overall survival were significantly longer in patients receiving ThaDD than in those treated with Thal-Dex. ThaDD regimen significantly improved response rate and overall survival in comparison with Thal-Dex. Although the frequency of hematologic toxicity and infections resulted higher in ThaDD group compared with control group, they were not particularly frequent after adequate prophylaxis was added and were easily managed when occurred.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/análogos & derivados , Mieloma Múltiple/tratamiento farmacológico , Polietilenglicoles/administración & dosificación , Talidomida/administración & dosificación , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Casos y Controles , Dexametasona/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Estudios de Seguimiento , Humanos , Liposomas , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Recurrencia , Estudios Retrospectivos , Terapia Recuperativa , Tasa de Supervivencia , Talidomida/efectos adversos , Resultado del TratamientoRESUMEN
We present the results of a phase 2 study using thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) in the treatment of 50 patients older than 65 years with newly diagnosed multiple myeloma. Thalidomide 100 mg was administered orally at bedtime continuously, dexamethasone 40 mg was administered orally on days 1 to 4 and 9 to 12, and pegylated liposomal doxorubicin 40 mg/m2 was administered intravenously on day 1 over the 28-day cycle. Response was assessed according to the EBMT criteria. Seventeen (34%) patients achieved CR, 7 (14%) nCR, 5 (10%) VGPR, 15 (30%) PR, and 5 (10%) MR, resulting in an ORR of 98%. Only 1 patient (2%) presented progressive disease. Time to progression (TTP), event-free survival (EFS), and overall survival (OS) projected at 3 years were 60%, 57%, and 74%, respectively, and these parameters were significantly higher in those patients achieving a response of at least VGPR versus those who did not. Grade 3 and 4 nonhematologic adverse events were constipation (10%), fatigue (6%), tremors (4%), mucositis (4%), and palmar-plantar erythrodysesthesia (2%). Grade 3 and 4 neutropenia occurred in 12% of patients. Grade 3 and 4 infections and thromboembolic accidents were observed in 22% and 14% of patients, respectively. In the treatment of elderly patients with newly diagnosed multiple myeloma, ThaDD is a very effective regimen with manageable toxicity.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Antineoplásicos Hormonales/farmacología , Dexametasona/farmacología , Doxorrubicina/análogos & derivados , Mieloma Múltiple/tratamiento farmacológico , Polietilenglicoles/farmacología , Talidomida/farmacología , Anciano , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Doxorrubicina/farmacología , Femenino , Humanos , Masculino , Estudios Prospectivos , Inducción de Remisión , Resultado del TratamientoRESUMEN
The objective of this study was to assess the utility of C-reactive protein (CRP) on differential diagnosis of pulmonary infiltrates occurring in 143 febrile patients with hematologic malignancies. Serum CRP level, measured on the first day of pneumonia, was significantly higher in patients with fungal lung infiltrates than in those with nonfungal pneumonia (22.3 mg/dl vs 7.3 mg/dl; p<0.0001). Predictive factors for fungal pneumonia were CRP level higher than 10 mg/dl, neutropenia longer than 10 days, and active underlying disease.
Asunto(s)
Proteína C-Reactiva/análisis , Neoplasias Hematológicas/complicaciones , Enfermedades Pulmonares Fúngicas/diagnóstico , Neumonía/diagnóstico , Adulto , Anciano , Análisis de Varianza , Biomarcadores/sangre , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Bacteriana/diagnóstico , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y Especificidad , Estadísticas no ParamétricasRESUMEN
The aim of this prospective, multicenter, phase II study was to investigate the combination of pegylated liposomal doxorubicin (Caelyx) 40 mg/m2 on day 1 every 28 days, dexamethasone 40 mg p.o. on days 1-4 and 9-12 and thalidomide 100 mg daily in 50 patients with advanced multiple myeloma. Twenty-six percent of patients achieved a complete response, 6% a near complete response, 6% a very good partial response, 38% a partial response, 16% a minor response and 8% progressed, for an overall response rate of 92%. The median event-free survival was 17 months and the median overall survival was not reached. Grade 3 non-hematologic toxicity occurred in 12% of patients, thromboembolic disease in 12% and severe infection in 16%. The combination of pegylated liposomal doxorubicin, dexamethasone an thalidomide is safe and very effective in advanced multiple myeloma.