RESUMEN
BACKGROUND: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment. We tested this hypothesis in a phase II study. PATIENTS AND METHODS: We enrolled 25 patients with relapsed/refractory HL with a median age of 42 years and who had previously received a median of five therapies including 18 (72%) with failed autologous stem cell transplant, 23 (92%) with failed brentuximab vedotin, and 11 (44%) with prior radiation therapy. Idelalisib was administered at 150 mg two times daily; an increase to 300 mg two times daily was permitted at the time of disease progression. RESULTS: The overall response rate to idelalisib therapy was 20% (95% confidence interval: 6.8%, 40.7%) with a median time to response of 2.0 months. Seventeen patients (68%) experienced reduction in target lesions with one complete remission and four partial remissions. The median duration of response was 8.4 months and median progression-free survival was 2.3 months. The most common grade ≥3 adverse event was elevation of alanine aminotransferase (two patients, 8%). Diarrhea/colitis was seen in three patients and was grade 1-2. There was one adverse event leading to death (hypoxia). CONCLUSIONS: Idelalisib was tolerable and had modest single-agent activity in heavily pretreated patients with HL. Rational combinations with other novel agents may improve response rate and duration of response. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov # NCT01393106.
Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/genética , Enfermedad de Hodgkin/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Purinas/administración & dosificación , Quinazolinonas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/fisiopatología , Femenino , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Purinas/efectos adversos , Quinazolinonas/efectos adversosRESUMEN
BACKGROUND: Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT. METHODS: In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic score was then validated in an independent clinical sample (part II). RESULTS: In part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [Asunto(s)
Trasplante de Células Madre Hematopoyéticas
, Enfermedad de Hodgkin/terapia
, Análisis de Supervivencia
, Adulto
, Anciano
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Pronóstico
, Modelos de Riesgos Proporcionales
, Recurrencia
, Factores de Riesgo
RESUMEN
OBJECTIVES: To evaluate the recommendations for multiparametric prostate MRI (mp-MRI) interpretation introduced in the recently updated Prostate Imaging Reporting and Data System version 2 (PI-RADSv2), and investigate the impact of pathologic tumour volume on prostate cancer (PCa) detectability on mpMRI. METHODS: This was an institutional review board (IRB)-approved, retrospective study of 150 PCa patients who underwent mp-MRI before prostatectomy; 169 tumours ≥0.5-mL (any Gleason Score [GS]) and 37 tumours <0.5-mL (GS ≥4+3) identified on whole-mount pathology maps were located on mp-MRI consisting of T2-weighted imaging (T2WI), diffusion-weighted (DW)-MRI, and dynamic contrast-enhanced (DCE)-MRI. Corresponding PI-RADSv2 scores were assigned on each sequence and combined as recommended by PI-RADSv2. We calculated the proportion of PCa foci on whole-mount pathology correctly identified with PI-RADSv2 (dichotomized scores 1-3 vs. 4-5), stratified by pathologic tumour volume. RESULTS: PI-RADSv2 allowed correct identification of 118/125 (94 %; 95 %CI: 90-99 %) peripheral zone (PZ) and 42/44 (95 %; 95 %CI: 89-100 %) transition zone (TZ) tumours ≥0.5 mL, but only 7/27 (26 %; 95 %CI: 10-42 %) PZ and 2/10 (20 %; 95 %CI: 0-52 %) TZ tumours with a GS ≥4+3, but <0.5 mL. DCE-MRI aided detection of 4/125 PZ tumours ≥0.5 mL and 0/27 PZ tumours <0.5 mL. CONCLUSIONS: PI-RADSv2 correctly identified 94-95 % of PCa foci ≥0.5 mL, but was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL. DCE-MRI offered limited added value to T2WI+DW-MRI. KEY POINTS: ⢠PI-RADSv2 correctly identified 95 % of PCa foci ≥0.5 mL ⢠PI-RADSv2 was limited for the assessment of GS ≥4+3 tumours ≤0.5 mL ⢠DCE-MRI offered limited added value to T2WI+DW-MRI.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Sistemas de Información Radiológica , Anciano , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Próstata/diagnóstico por imagen , Próstata/patología , Estudios RetrospectivosRESUMEN
AIM: To determine the accuracy of 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) in the detection of advanced colorectal adenomas. MATERIALS AND METHODS: In this retrospective study, patient consent was waived by the institutional review board. Combined FDG whole-body PET and computed tomography (CT) images (2000-2009) were re-read and compared with reports of complete colonoscopy performed up to 1 year after the PET examination. One or more areas of focal colonic uptake greater than the background indicated a positive PET result, irrespective of standardized uptake value (SUV). Lesion and patient-level measures of PET accuracy with their 95% confidence intervals (CI) were calculated. RESULTS: One hundred and eighty patients undergoing colonoscopy with or without biopsy underwent PET within 1 year prior to colonoscopy. There were 92 women and 88 men (mean age 63.3 years). Indications for PET were extent of disease and treatment response in all cases. Patients had non-colorectal cancer (n = 160) or colon cancer (n = 20). One hundred and fourteen FDG-avid lesions were present. In 33, there was no colonoscopic correlate. Two hundred and fifty-eight biopsies revealed tubular adenomas (n = 91, one with intra-mucosal cancer), tubulovillous adenomas (n = 28), adenocarcinoma (n = 37), inflammation (n = 22), hyperplastic polyps (n = 54), serrated adenoma (n = 5), metastatic disease (n = 5), normal/benign mucosa or submucosal benign tumors (n = 13) or miscellaneous (n = 3). Per-lesion performance of PET showed a sensitivity of 38% (95% CI: 31-46; 64/167) for all adenomas and carcinomas and 58% (95% CI: 49-67; 57/98) for lesions ≥ 10 mm. At the patient level, for all adenomas and carcinomas the sensitivity was 54% (95% CI: 44-63; 61/113), specificity 100% (pre-defined), positive predictive value (PPV) 100% (pre-defined), and negative predictive value (NPV) 56% (95% CI: 47-65; 67/119). For patients with advanced adenoma, PET sensitivity was 49% (95% CI: 35-63; 26/53) specificity, 100%, PPV 100% and NPV 82% (95% CI: 76-88; 127/154). Five of 37 adenocarcinomas were not detected, one of which was mucinous at histology. CONCLUSION: FDG PET detected most cancers, but only identified one-half of patients harbouring advanced adenomas. Based on the data, PET cannot be relied upon to accurately identify patients with advanced adenoma.
Asunto(s)
Adenoma/diagnóstico por imagen , Neoplasias Colorrectales/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Radiofármacos , Adenoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Pólipos del Colon/diagnóstico por imagen , Pólipos del Colon/cirugía , Colonoscopía/estadística & datos numéricos , Neoplasias Colorrectales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Tomografía de Emisión de Positrones/métodos , Estudios Retrospectivos , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodosRESUMEN
Hallucinations, delusions, and compulsive behaviors are frequent iatrogenic complications of the treatment of motor dysfunction in Parkinson's disease (PD). Although these have been studied, and the phenomenology described, there are few detailed descriptions of the various psychiatric problems our treated PD patients live with that allow physicians who do not have a great deal of experience with PD patients to appreciate the extent of their altered lives. This report is a compilation of vignettes describing these behavioral problems that the treating neurologist or psychiatrist attributed to the medications used for treating PD.
Asunto(s)
Antiparkinsonianos/efectos adversos , Carbidopa/efectos adversos , Conducta Compulsiva/inducido químicamente , Deluciones/inducido químicamente , Alucinaciones/inducido químicamente , Levodopa/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Escalas de Valoración PsiquiátricaRESUMEN
BACKGROUND: Minimal residual disease (MRD) monitoring has been used to identify early molecular relapse and predict clinical relapse in mantle cell lymphoma (MCL). Few published data exist in MCL on the performance of next-generation sequencing-based assay of immunoglobulin gene rearrangements for MRD assessment. PATIENTS AND METHODS: In a prospective clinical trial (NCT01484093) with intensive induction chemotherapy and autologous stem-cell transplantation, posttreatment peripheral blood samples were collected from 16 MCL patients and analyzed with an earlier version of the Adaptive Biotechnologies MRD assay. RESULTS: Of the 7 patients whose disease remained in remission, the MRD test remained negative in 5 (71%). Of the 9 patients who experienced relapse, the MRD test was positive at least 3 months before relapse in 6 patients (67%) and positive at the time of relapse in 1 patient (11%). All patients with at least 2 positive MRD tests experienced relapse. CONCLUSION: The next-generation sequencing-based MRD assay identified early molecular relapse, and we observed more sensitivity in the cellular (circulating leukocytes) versus acellular (plasma cell-free DNA) compartment. This observation may be due to availability of tumor target or a limitation of the assay.
Asunto(s)
ADN de Neoplasias/sangre , Linfoma de Células del Manto/sangre , Linfoma de Células del Manto/diagnóstico , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/diagnóstico , Anciano , Quimioradioterapia , Femenino , Reordenamiento Génico , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunoglobulinas/genética , Inmunoterapia , Quimioterapia de Inducción , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Neoplasia Residual , Células Neoplásicas Circulantes , Estudios Prospectivos , Inducción de Remisión , Trasplante de Células Madre , Trasplante AutólogoRESUMEN
BACKGROUND: The proliferative index (PI) is a powerful prognostic factor in mantle cell lymphoma (MCL); however, its utility is hampered by interobserver variability. The mantle cell international prognostic index (MIPI) has been reported to have prognostic importance. In this study, we determined the prognostic value of the PI as determined by quantitative image analysis in MCL. PATIENTS AND METHODS: Eighty-eight patients with adequate tissue were included in this analysis. Patients were treated with one of two treatment programs: sequential therapy with high-dose therapy consolidation or radioimmunotherapy followed by combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone. Patients were divided into four groups based on PI (<10%, 10%-29.9%, 30%-49.9%, and >50%), and outcomes were analyzed. RESULTS: Thirty percent was identified as the optimal cut-off for PI. By univariate analysis, intensive treatment and a low PI were associated with a superior progression-free survival (PFS); only PI was associated with overall survival. By multivariate analysis, both intensive treatment and PI correlated with PFS. The MIPI had no prognostic impact. CONCLUSIONS: PI is the most important prognostic factor in MCL. The cut-off of 30% is clinically meaningful and can be used to tailor the intensity of therapy in future clinical trials.
Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Antígeno Ki-67/análisis , Linfoma de Células del Manto/mortalidad , Linfoma de Células del Manto/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Proliferación Celular/efectos de los fármacos , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Linfoma de Células del Manto/tratamiento farmacológico , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: The Stanford group has reported excellent results with the Stanford V regimen for patients with bulky and/or advanced Hodgkin lymphoma (HL). However, Gobbi reported markedly inferior failure-free survival (FFS) comparing Stanford V to other regimens but included major deviations from the original program. We retrospectively examined whether treatment at our institution carefully following Stanford V guidelines would confirm the original Stanford outcome data. PATIENTS AND METHODS: From June 1995 to May 2002, 126 patients with either locally extensive or advanced HL were treated with the 12-week Stanford V chemotherapy program followed by 36-Gy involved-field radiotherapy to sites initially > or =5 cm and/or to macroscopic splenic disease. Overall, 26% had stage IV disease and 20% had international prognostic score (IPS) > or =4. Overall survival (OS), disease-specific survival, progression-free survival (PFS), FFS, and freedom from second relapse (FF2R) were determined. RESULTS: The 5- and 7-year OS were 90% and 88%, respectively. The 5-year FFS was 78%. IPS > or =4 was a significant independent predictor of worse OS and PFS. The FF2R was 64% at 3 years. CONCLUSION: Stanford V with appropriate radiotherapy is a highly effective regimen for locally extensive and advanced HL.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/terapia , Recurrencia Local de Neoplasia/terapia , Adolescente , Adulto , Anciano , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Estadificación de Neoplasias , Estudios Retrospectivos , Terapia Recuperativa , Tasa de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Torsion dystonia is a movement disorder of unknown etiology characterized by loss of control of voluntary movements appearing as sustained muscle contractions and/or abnormal postures. Dystonic movements can be caused by lesions in the basal ganglia, drugs, or gene defects. Several hereditary forms have been described, most of which have autosomal dominant transmission with variable expressivity. In the Ashkenazi Jewish population the defective gene frequency is about 1/10,000. Here, linkage analysis using polymorphic DNA and protein markers has been used to locate a gene responsible for susceptibility to dystonia in a large, non-Jewish kinship. Affected members of this family have a clinical syndrome similar to that found in the Jewish population. This dystonia gene (ITD1) shows tight linkage with the gene encoding gelsolin, an actin binding protein, and appears by multipoint linkage analysis to lie in the q32-q34 region of chromosome 9 between ABO and D9S26, a region that also contains the locus for dopamine-beta-hydroxylase.
Asunto(s)
Cromosomas Humanos Par 9 , Distonía Muscular Deformante/genética , Polimorfismo de Longitud del Fragmento de Restricción , Proteínas de Unión al Calcio/genética , Mapeo Cromosómico , Sondas de ADN , Dopamina beta-Hidroxilasa/genética , Gelsolina , Ligamiento Genético , Marcadores Genéticos , Humanos , Proteínas de Microfilamentos/genética , LinajeRESUMEN
INTRODUCTION: HDT/ASCT is standard for relapsed and refractory DLCL patients responding to second-line chemotherapy. We incorporated a thrombopoietic agent into the ICE chemotherapy program to potentially: decrease platelet associated toxicities, augment stem cell collection and maintain dose intensity. METHODS: This randomized, double-blind, placebo-controlled phase I/II trial examines PEG-rHuMGDF versus placebo with ICE chemotherapy. Phase I compared three cohorts and defined a clinically effective dose (CED). Phase II evaluated the CED versus placebo. Outcome measures included safety, hematological end-points, stem cell collection and the impact of dose-intensity on outcome. RESULTS: Forty-one patients with primary refractory (16) or relapsed DLCL (25) were treated; Response rates for evaluable patients are: 75% (12/16) for placebo and 82% (18/22) for PEG-rHuMGDF. PEG-rHuMGDF treated patients had significantly less grade IV thrombocytopenia, higher median platelet nadirs, and less platelet transfusion per cycle. ICE dose intensity was improved with PEG-rHuMGDF versus placebo: 75 versus 42% (P = 0.008). At 8.5 years median follow-up, overall and event-free survival are 47 and 31%, respectively. Patients treated on PEG-rHuMGDF versus placebo had improved survival (59 versus 31%, P = 0.06). CONCLUSION: PEG-rHuMGDF ameliorated thrombocytopenia, improved platelet recovery, and maintained ICE dose intensity. Potential survival advantages conferred by maintaining dose intensity require validation with newer thrombopoietic agents.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Polietilenglicoles/administración & dosificación , Trombopoyetina/administración & dosificación , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Resistencia a Antineoplásicos , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Estado de Ejecución de Karnofsky , Linfoma no Hodgkin/patología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Probabilidad , Pronóstico , Proteínas Recombinantes/administración & dosificación , Valores de Referencia , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma. Rhabdomyosarcoma, the most common soft tissue sarcoma of childhood. makes up less than 1% of solid malignancies in adults with around 400 new cases each year in the United States. They have not previously been reported concurrently. CASE PRESENTATION: A 37 year old woman presented with painful enlarging leg mass. Biopsy of the mass was consistent with embryonal rhabdomyosarcoma. Staging imaging revealed a PET avid anterior mediastinal lymph node. Excisional biopsy of this mass was consistent with diffuse large B-cell lymphoma. Hybridization capture-based next-generation DNA sequencing did not reveal shared somatic tumor mutations. Germline analysis did not show identifiable aberrations of TP53 or other heritable cancer susceptibility genes. She was treated with a personalized chemotherapy regimen combining features of R-CHOP and Children's Oncology Group ARST 0331. CONCLUSIONS: This case illustrates a unique clinical entity successfully treated with a personalized chemotherapeutic regimen.
RESUMEN
In the CORAL study, 255 chemosensitive relapses with diffuse large B-cell lymphoma (DLBCL) were consolidated with autologous stem cell transplantation (ASCT), and 75 of them relapsed thereafter. The median time between ASCT and progression was 7.1 months. The median age was 56.1 years; tertiary International Prognosis Index (tIPI) observed at relapse was 0-2 in 71.6% of the patients and >2 in 28.4%. The overall response rate to third-line chemotherapy was 44%. The median overall survival (OS) was 10.0 months (median follow-up: 32.8 months). Thirteen patients received an allogeneic SCT, and three a second ASCT. The median OS was shorter among patients who relapsed <6 months (5.7 months) compared with those relapsing ⩾12 months after ASCT (12.6 months, P=0.0221). The median OS in patients achieving CR, PR or no response after the third-line regimen was 37.7 (P<0.0001), 10.0 (P=0.03) and 6.3 months, respectively. The median OS varied according to tIPI: 0-2: 12.6 months and >2: 5.3 months (P=0.0007). In multivariate analysis, tIPI >2, achievement of response and remission lasting <6 months predicted the OS. This report identifies the prognostic factors for DLBCL relapsing after ASCT and thus helps to select patients for experimental therapy.
Asunto(s)
Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/terapia , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Tasa de SupervivenciaRESUMEN
PURPOSE: To examine the correlations between uni-dimensional RECIST and volumetric measurements in patients with lung adenocarcinoma and to assess their association with overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: In this study of patients receiving chemotherapy for lung cancer in the setting of a clinical trial, response was prospectively evaluated using RECIST 1.0. Retrospectively, volumetric measurements were recorded and response was assessed by two different volumetric methods at each followup CT scan using a semi-automated segmentation algorithm. We subsequently evaluated the correlation between the uni-dimensional RECIST measurements and the volumetric measurements and performed landmark analyses for OS and PFS at the completion of the first and second follow-ups. Kaplan-Meier curves together with log-rank tests were used to evaluate the association between the different response criteria and patient outcome. RESULTS: Forty-two patients had CT scans at baseline, after the first follow up scan and second followup scan, and then every 8 weeks. The uni-dimensional RECIST measurements and volumetric measurements were strongly correlated, with a Spearman correlation coefficient (ρ) of 0.853 at baseline, ρ=0.861 at the first followup, ρ=0.843 at the 2nd followup, and ρ=0.887 overall between-subject. On first follow-up CT, partial responders and non responders as assessed by an "ellipsoid" volumetric criteria showed a significant difference in OS (p=0.008, 1-year OS of 70% for partial responders and 46% for non responders). There was no difference between the groups when assessed by RECIST criteria on first follow-up CT (p=0.841, 1-year OS rate of 64% for partial responders and 64% for non responders). CONCLUSION: Volumetric response on first follow-up CT may better predict OS than RECIST response. CLINICAL RELEVANCE STATEMENT: Assessment of tumor size and response is of utmost importance in clinical trials. Volumetric measurements may help to better predict OS than uni-dimensional RECIST criteria.
Asunto(s)
Adenocarcinoma/diagnóstico por imagen , Tomografía Computarizada de Haz Cónico/métodos , Neoplasias Pulmonares/diagnóstico por imagen , Criterios de Evaluación de Respuesta en Tumores Sólidos , Adenocarcinoma del Pulmón , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard second-line treatment for relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, the strategy is less clear in patients who require third-line treatment. Updated outcomes of 203 patients who could not proceed to scheduled ASCT in the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) are herein reviewed. In the intent-to-treat analysis, overall response rate to third-line chemotherapy was 39%, with 27% CR or CR unconfirmed, and 12% PR. Among the 203 patients, 64 (31.5%) were eventually transplanted (ASCT 56, allogeneic SCT 8). Median overall survival (OS) of the entire population was 4.4 months. OS was significantly improved in patients with lower tertiary International Prognostic Index (IPI), patients responding to third-line treatment and patients transplanted with a 1-year OS of 41.6% compared with 16.3% for the not transplanted (P<0.0001). In multivariate analysis, IPI at relapse (hazard ratio (HR) 2.409) and transplantation (HR 0.375) independently predicted OS. Third-line salvage chemotherapy can lead to response followed by transplantation and long-term survival in DLBCL patients. However, improvement of salvage efficacy is an urgent need with new drugs.
Asunto(s)
Linfoma de Células B Grandes Difuso/mortalidad , Linfoma de Células B Grandes Difuso/terapia , Terapia Recuperativa/métodos , Trasplante de Células Madre , Adolescente , Adulto , Anciano , Autoinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recurrencia , Tasa de SupervivenciaRESUMEN
PURPOSE: The results of laparoscopic procedures on patients with suspected or known lymphoma were analyzed to review the application and define the role of laparoscopy in lymphoma. PATIENTS AND METHODS: The hospital records of 94 patients who underwent 101 procedures between June 1993 and October 1996 were reviewed for demographic and clinicopathologic information. RESULTS: The procedure was diagnostic in 85 patients, either at primary presentation (48 patients), possible relapse (21 patients), in the course of treatment (eight patients), or of a liver lesion (eight patients). In the remaining 16 patients, it was used to stage possible intraabdominal disease. Twenty-seven patients had a previous unsuccessful diagnostic procedure. There were no operative deaths and eight postoperative complications (8%). The laparoscopy revealed non-Hodgkin's lymphoma (NHL) in 48 patients, Hodgkin's disease (HD) in 14 patients, other neoplastic conditions in six patients, and benign conditions in 33 patients. There was adequate information in all procedures in which lymphoma was diagnosed for treatment decisions. There was one false-negative and one nonresult for technical reasons. Ten patients commenced chemotherapy before discharge after a median delay of 3.5 days. In five of 24 patients (21%) with recurrent or persistent lymphoma, the precise diagnosis was significantly different from the original one. CONCLUSION: From our experience, laparoscopy can safely provide tissue samples of suspected lymphoma for full diagnostic analysis. It should be considered when percutaneous biopsy is not technically possible, when chromosomal or genetic analysis is needed for treatment decisions, or when the results of percutaneous biopsy are inadequate to make therapeutic decisions.
Asunto(s)
Neoplasias Abdominales/diagnóstico , Laparoscopía , Linfoma/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Niño , Femenino , Humanos , Hígado/patología , Ganglios Linfáticos/patología , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To evaluate a chemotherapy regimen that consisted of ifosfamide administered as an infusion with bolus carboplatin, and etoposide (ICE) supported by granulocyte colony-stimulating factor (G-CSF) for cytoreduction and stem-cell mobilization in transplant-eligible patients with primary refractory or relapsed non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: One hundred sixty-three transplant-eligible patients with relapsed or primary refractory NHL were treated from October 1993 to December 1997 with ICE chemotherapy at Memorial Sloan-Kettering Cancer Center. Administration of three cycles of ICE chemotherapy was planned at 2-week intervals. Peripheral-blood progenitor cells were collected after cycle 3, and all patients who achieved a partial response (PR) or complete response (CR) to ICE chemotherapy were eligible to proceed to transplantation. Event-free and overall survival, ICE-related toxicity, and the number of CD34(+) cells collected after treatment with ICE and G-CSF were evaluated. RESULTS: All 163 patients were assessable for response, and there was no treatment-related mortality. A major response (CR/PR) was evident in 108 patients (66.3%); 89% of the responding patients underwent successful transplantation. Patient who underwent transplantation and achieved a CR to ICE had a superior overall survival to that of patients who achieved a PR (65% v 30%; P =.003). The median number of CD34(+) cells/kg collected was 8.4 x 10(6). The dose-limiting toxicity of ICE was hematologic, with 29.4% of patients developing grade 3/4 thrombocytopenia. There were minimal nonhematologic side effects. CONCLUSION: ICE chemotherapy, with ifosfamide administered as a 24-hour infusion to decrease CNS side effects, and the substitution of carboplatin for cisplatin to minimize nephrotoxicity, is a very effective cytoreduction and mobilization regimen in patients with NHL. Furthermore, the quality of the clinical response to ICE predicts for posttransplant outcome.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Movilización de Célula Madre Hematopoyética , Linfoma no Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Movimiento Celular , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Leucocitos Mononucleares/inmunología , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Células Madre/fisiologíaRESUMEN
The quantity of hematopoietic progenitors in an apheresis collection is defined by the number of CD34(+) cells or granulocyte macrophage colony-forming units present. These parameters are believed to give roughly equivalent information on graft quality. We here report that the in vitro proliferative potential of r-metHuSCF (stem cell factor) plus filgrastim (granulocyte colony-stimulating factor; r-metHuG-CSF) mobilized peripheral blood (PB) CD34(+) cells obtained from previously heavily treated non-Hodgkin's lymphoma patients inversely correlates with extent of prior therapy. CD34(+) cells were enriched using the CellPro Ceprate system and placed in liquid culture for 4 weeks in the presence of either r-metHuSCF, IL-3, IL-6, filgrastim (S36G), or S36G plus erythropoietin (S36GE) with a weekly exchange of media and cytokines with reestablishment of culture at the starting cell concentration (Delta assay) and enumeration of progenitors. Starting with 4 x 10(4) CD34(+) cells from apheresis samples from patients who had received <10 cycles of prior chemotherapy, progenitors were detectable in culture at 4 weeks 81% of the time as compared to 14% with CD34(+) cells from patients who had received >10 cycles and 5% for >10 cycles plus radiotherapy. The total number of progenitors generated over the duration of culture (area under the curve) was calculated using the trapezoidal rule as a novel measure of the proliferative potential of the enriched PB CD34(+) cell population. The median area under the curve of CD34(+) cells from patients receiving <10 cycles of prior chemotherapy was 7.4 and 5.7 (x10(5)) using S36G or S36GE, respectively, 1.8 and 1.9 if the patients received >10 cycles of prior chemotherapy, and 1.4 and 1.2 if the patients received >10 cycles of prior chemotherapy plus radiotherapy (P < 0.001). These data show that prior therapy impacts on the quality of PB CD34(+) cells as measured by their ability to generate committed progenitors over a number of weeks in liquid culture.
Asunto(s)
Factor Estimulante de Colonias de Granulocitos/farmacología , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas/efectos de los fármacos , Linfoma no Hodgkin/patología , Factor de Células Madre/análogos & derivados , Antígenos CD34/análisis , Área Bajo la Curva , División Celular , Ensayo de Unidades Formadoras de Colonias , Filgrastim , Trasplante de Células Madre Hematopoyéticas , Humanos , Interleucina-3/farmacología , Interleucina-6/farmacología , Leucaféresis , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/terapia , Proteínas Recombinantes/farmacología , Factor de Células Madre/farmacologíaRESUMEN
The objective of this study was to identify factors associated with poor mobilization of peripheral blood progenitor cells (PBPCs) or delayed platelet engraftment after high-dose therapy and autologous stem cell transplantation in patients with lymphoma. Fifty-eight patients with Hodgkin's disease or non-Hodgkin's lymphoma underwent PBPC transplantation as the "best available therapy" at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1993 and 1995. PBPCs were mobilized with either granulocyte colony-stimulating factor (G-CSF) alone (n = 19) or G-CSF following combination chemotherapy (n = 39). Forty-eight of these patients underwent a PBPC transplant, receiving a conditioning regimen containing cyclophosphamide, etoposide, and either total body irradiation, total lymphoid irradiation, or carmustine. A median number of 4.6 x 10(6) CD34+ cells/kg were obtained with a median of three leukapheresis procedures. Mobilization of PBPCs using chemotherapy plus G-CSF was superior to G-CSF alone (6.7 x 10(6) versus 1.5 x 10(6) CD34+ cells/kg; P = 0.0002). Poorer mobilization of progenitor cells was observed in patients who had previously received stem cell-toxic chemotherapy, including (a) nitrogen mustard, procarbazine, melphalan, carmustine or > 7.5 g of cytarabine chemotherapy premobilization (2.0 x 10(6) versus 6.0 x 10(6) CD34+ cells/kg; P = 0.005), or (b) > or = 11 cycles of any previous chemotherapy (2.6 x 10(6) versus 6.7 x 10(6) CD34+ cells/kg; P = 0.02). Platelet recovery to > 20,000/microliter was delayed in patients who received < 2.0 x 10(6) CD34+ cells (median, 13 versus 22 days; P = 0.06). Patients who received > or = 11 cycles of chemotherapy prior to PBPC mobilization tended to have delayed platelet recovery to > 20,000/microliter and to require more platelet transfusions than less extensively pretreated patients (median, 13.5 versus 23.5 days; P = 0.15; median number of platelet transfusion episodes, 13 versus 9; P = 0.17). These data suggest that current strategies to mobilize PBPCs may be suboptimal in patients who have received either stem cell-toxic chemotherapy or > or = 11 cycles of chemotherapy prior to PBPC mobilization. Alternative approaches, such as ex vivo expansion or the use of other growth factors in addition to G-CSF, may improve mobilization of progenitor cells for PBPC transplantation.