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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células del Manto/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Estudios de Seguimiento , Humanos , Linfoma de Células del Manto/radioterapia , Prednisona/uso terapéutico , Radioinmunoterapia/métodos , Rituximab , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: The role of body mass index (BMI) in survival outcomes is controversial among lymphoma patients. We evaluated the association between BMI at study entry and failure-free survival (FFS) and overall survival (OS) in three phase III clinical trials, among patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin's lymphoma (HL). PATIENTS AND METHODS: A total of 537, 730 and 282 patients with DLBCL, HL and FL were included in the analysis. Baseline patient and clinical characteristics, treatment received and clinical outcomes were compared across BMI categories. RESULTS: Among patients with DLBCL, HL and FL, the median age was 70, 33 and 56; 29%, 29% and 37% were obese and 38%, 27% and 37% were overweight, respectively. Age was significantly different among BMI groups in all three studies. Higher BMI groups tended to have more favorable prognosis factors at study entry among DLBCL and HL patients. BMI was not associated with clinical outcome with P-values of 0.89, 0.30 and 0.40 for FFS, and 0.64, 0.67 and 0.09 for OS, for patients with DLBCL, HL and FL, respectively. The association remains non-significant after adjusting for other clinical factors in the Cox model. A subset analysis of males with DLBCL treated on R-CHOP revealed no differences in FFS (P = 0.48) or OS (P = 0.58). CONCLUSION: BMI was not significantly associated with clinical outcomes among patients with DLBCL, HD or FL, in three prospective phase III clinical trials. The findings contradict some previous reports of similar investigations. Further work is required to understand the observed discrepancies.
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Índice de Masa Corporal , Enfermedad de Hodgkin/mortalidad , Linfoma Folicular/mortalidad , Linfoma de Células B Grandes Difuso/mortalidad , Obesidad/mortalidad , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Estudios Prospectivos , Rituximab , Resultado del Tratamiento , Estados Unidos , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: Treatment options for patients with nonbulky stage IA-IIA Hodgkin lymphoma include combined modality therapy (CMT) using doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) plus involved-field radiation therapy (IFRT), and chemotherapy with ABVD alone. There are no mature randomized data comparing ABVD with CMT using modern radiation techniques. PATIENTS AND METHODS: Using German Hodgkin Study Group HD10/HD11 and NCIC Clinical Trials Group HD.6 databases, we identified 588 patients who met mutually inclusive eligibility criteria from the preferred arms of HD10 or 11 (n = 406) and HD.6 (n = 182). We evaluated time to progression (TTP), progression-free (PFS) and overall survival, including in three predefined exploratory subset analyses. RESULTS: With median follow-up of 91 (HD10/11) and 134 (HD.6) months, respective 8-year outcomes were for TTP, 93% versus 87% [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.24-0.78]; for PFS, 89% versus 86% (HR 0.71, 95% CI 0.42-1.18) and for overall survival, 95% versus 95% (HR 1.09, 95% CI 0.49-2.40). In the exploratory subset analysis including HD10 eligible patients who achieved complete response (CR) or unconfirmed complete response (CRu) after two cycles of ABVD, 8-year PFS was 87% (HD10) versus 95% (HD.6) (HR 2.8; 95% CI 0.64-12.5) and overall survival 96% versus 100%. In contrast, among those without CR/CRu after two cycles of ABVD, 8-year PFS was 88% versus 74% (HR 0.35; 95% CI 0.16-0.79) and overall survival 95% versus 91%, respectively (HR 0.42; 95% CI 0.12-1.44). CONCLUSIONS: In patients with nonbulky stage IA-IIA Hodgkin lymphoma, CMT provides better disease control than ABVD alone, especially among those not achieving complete response after two cycles of ABVD. Within the follow-up duration evaluated, overall survivals were similar. Longer follow-up is required to understand the implications of radiation and chemotherapy-related late effects. CLINICAL TRIALS: The trials included in this analysis were registered at ClinicalTrials.gov: HD10 - NCT00265018, HD11 - NCT00264953, HD.6 - NCT00002561.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adulto , Bleomicina/uso terapéutico , Quimioradioterapia , Dacarbazina/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Enfermedad de Hodgkin/mortalidad , Humanos , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Retrospectivos , Resultado del Tratamiento , Vinblastina/uso terapéuticoRESUMEN
INTRODUCTION: To assess the efficacy of an abbreviated Stanford V regimen in patients with early-stage Hodgkin lymphoma (HL). PATIENTS AND METHODS PATIENTS: with untreated nonbulky stage I-IIA supradiaphragmatic HL were eligible for the G4 study. Stanford V chemotherapy was administered for 8 weeks followed by radiation therapy (RT) 30 Gy to involved fields (IF). Freedom from progression (FFP), disease-specific survival (DSS) and overall survival (OS) were estimated. RESULTS: All 87 enrolled patients completed the abbreviated regimen. At a median follow-up of 10 years, FFP, DSS and OS are 94%, 99% and 94%, respectively. Therapy was well tolerated with no treatment-related deaths. CONCLUSIONS: Mature results of the abbreviated Stanford V regimen in nonbulky early-stage HL are excellent and comparable to the results from other contemporary therapies.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Adolescente , Adulto , Bleomicina/administración & dosificación , Terapia Combinada , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/patología , Humanos , Masculino , Mecloretamina/administración & dosificación , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
BACKGROUND AND AIMS: The results of class prediction and the determination of prognostic markers in diffuse large B-cell lymphoma (DLBCL) have been variably reported. Apart from biological variations, this may be caused by differences in laboratory techniques, scoring definitions and inter- and intra-observer variation. In this study, an international collaboration of clinical lymphoma research groups has concentrated on validation and standardisation of immunohistochemistry of the currently potentially interesting prognostic markers in DLBCL. METHODS: Sections of a tissue microarray with 36 cases of DLBCL were stained in eight laboratories with antibodies to CD20, CD5, bcl-2, bcl-6, CD10, HLA-DR, MUM-1 and Ki-67 according to local methods. The study was performed in two rounds, firstly focused on the evaluation of laboratory staining variation, and secondly on the scoring variation. RESULTS: Different techniques resulted in highly variable results and poor reproducibility for almost all markers. Reproducibility of the nuclear markers was highly sensitive to technical variations, including immunological enhancement techniques (agreements 34%). With elimination of variation due to staining and uniformly agreed on scoring criteria, significant improvement was seen; however less so for bcl-6 and Ki-67 (agreement 53-58%). Absence of internal controls that preclude scoring, significantly influenced the results for CD10 and bcl-6. CONCLUSION: Semi-quantitative immunohistochemistry for subclassification of DLBCL is feasible, but with varying rates of concordance for different markers and only using optimised techniques and strict scoring criteria. These findings may explain the wide variation in prognostic impact reported in the literature. Harmonisation of techniques and centralised consensus review appears mandatory when using immunohistochemical biomarkers for treatment stratification.
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Biomarcadores de Tumor/metabolismo , Linfoma de Células B Grandes Difuso/diagnóstico , Antígenos CD/metabolismo , Proteínas de Unión al ADN/metabolismo , Antígenos HLA-DR/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Linfoma de Células B Grandes Difuso/clasificación , Proteínas de Neoplasias/metabolismo , Variaciones Dependientes del Observador , Pronóstico , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6 , Reproducibilidad de los Resultados , Análisis de Matrices Tisulares/métodosRESUMEN
BACKGROUND: In the National Cancer Institute of Canada Clinical Trials Group/Eastern Cooperative Oncology Group HD.6 trial, progression-free survival was better in patients randomized to therapy that included radiation, compared to doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) alone. We now evaluate patterns of progression and subsequent outcomes of patients with progression. PATIENTS AND METHODS: After a median of 4.2 years, 33 patients have progressed. Two radiation oncologists determined whether sites of progression were confined within radiation fields. Freedom from second progression (FF2P) and freedom from second progression or death (FF2P/D) were compared. RESULTS: Reviewers agreed for the extended (kappa = 0.87) and involved field (kappa = 1.0) analyses. Progression after ABVD alone was more frequently confined within both the extended (20/23 vs. 3/10; P = 0.002) and involved fields (16/23 vs. 2/10; P = 0.02). There was no difference in FF2P between groups [5-year estimate 99% (radiation) versus 96% (ABVD alone)] [hazard ratio (HR) = 3.14, 95% confidence interval (CI) 0.63-15.6; P = 0.14]; the 5-year estimates of FF2P/D were 94% in each group (HR = 1.04, 95% CI 0.41-2.63; P = 0.93). CONCLUSION: Treatment that includes radiation reduces the risk of progressive Hodgkin lymphoma in sites that receive this therapy, but we are unable to detect differences in FF2P or FF2P/D.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Bleomicina/uso terapéutico , Dacarbazina/uso terapéutico , Progresión de la Enfermedad , Doxorrubicina/uso terapéutico , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Estadificación de Neoplasias , Resultado del Tratamiento , Vinblastina/uso terapéuticoRESUMEN
This paper examines the evidence available to guide treatment decisions in three areas of Hodgkin's lymphoma management. In Section I Dr. Evert Noordijk describes evolving strategies for patients with early stage disease outlining the eras during which the focus has changed from initially accomplishing cure through refining and intensifying the treatment to one of maximizing cure rates and finally into a patient-oriented era in which the twin goals of maintaining high rates of cure and minimizing late toxicity are being achieved. In Section II Dr. Sandra Horning reviews the way in which the cooperative groups of North America and Europe have built upon initial observations from single centers to assemble the trials that have defined the treatment for advanced stage Hodgkin's lymphoma. Over a period of almost three decades, these well-constructed trials have defined a current standard of treatment, ABVD chemotherapy and are now investigating innovative approaches to move beyond this standard. She also indicates the need to appreciate diagnostic factors and the implications of prognostic factor models for the design and interpretation of clinical trials. In Section III Dr. Joseph Connors summarizes the evidence available to inform our choice of treatment for the uncommon but important entity of lymphocyte predominance Hodgkin's lymphoma. Once again, the guidance that can be derived from carefully conducted clinical investigation is used to address the issues surrounding choice of treatment, reasonable monitoring in long term follow-up and the clear-cut need to base diagnosis on objective immunohistochemical evidence.
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Enfermedad de Hodgkin/terapia , Terapia Combinada , Medicina Basada en la Evidencia , Enfermedad de Hodgkin/clasificación , Humanos , Radioterapia Adyuvante , Resultado del TratamientoRESUMEN
A retrospective analysis was performed to investigate the outcome of high-dose therapy (HDT) and autologous hematopoietic cell transplantation in patients with follicular lymphomas beyond first remission. Ninety-two patients with primary induction failure or relapsed follicular low-grade lymphoma (FLGL), follicular large cell lymphoma (FLCL), and transformed follicular lymphoma (TFL) were treated with myeloablative therapy consisting of etoposide (60 mg/kg), cyclophosphamide (100 mg/kg), and either carmustine (BCNU;15 mg/kg) or fractionated total body irradiation (FTBI; 1200 cGy) followed by transplantation of purged autologous bone marrow or peripheral blood hematopoietic cells. For the 49 patients with relapsed FLGL, the median age was 49 years and the median interval from diagnosis to HDT was 30 months. The 4-year estimate of overall survival (OS) was 60% (95% confidence interval [CI], 45%-75%) and of disease-free survival (DFS) was 44% (95% CI, 29%-59%). Treatment with the FTBI-containing HDT regimen was associated with significantly longer DFS (P = .04) and OS (P = .04) in our multivariate analysis. OS was also significantly longer among those treated with 3 or fewer chemotherapy regimens. For the 26 FLCL patients, the median age was 51 years and in 31% the indication for HDT was primary induction failure. For FLCL patients, the 4-year estimate of OS was 58% (95% CI, 37%-79%) and of DFS was 51% (95% CI, 30%-72%). Among the 17 patients with TFL, 13 (76%) transformed at first relapse, and only 6 patients (35%) achieved complete remission with salvage therapy prior to HDT. For TFL patients, the 4-year estimate of OS was 50% (95% CI, 24%-76%) and of DFS 49% (95% CI, 20%-78%). There were 3 occurrences of myelodysplasia (1 after treatment with TBI, 2 after BCNU treatment), yielding an estimated incidence of 7% (95% CI, 0%-16%) at 56 months. This analysis shows that relapsed FLGL patients treated with 3 or fewer different chemotherapy regimens show inferior survival. The HDT regimen containing FTBI appears to be superior to the BCNU-based regimen for relapsed FLGL, although longer follow-up is needed to evaluate late effects. Lastly, patients with TFL or induction failure and relapsed FLCL can achieve survival outcome comparable to those observed with the indolent follicular lymphomas.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Linfoma Folicular/terapia , Adulto , Anciano , Carmustina/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , Linfoma Folicular/clasificación , Linfoma Folicular/complicaciones , Masculino , Persona de Mediana Edad , Defectos del Tubo Neural/etiología , Pronóstico , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento , Irradiación Corporal TotalRESUMEN
Advanced stage follicular small cleaved and mixed cell lymphoma is characterized by relapse from remission and survival ranging from 6 to 12 years. Because young patients have the greatest compromise in longevity, the efficacy and toxicity of high-dose radiochemotherapy and bone marrow transplantation after conventional chemotherapy was evaluated in a prospective phase II clinical trial. Thirty-seven patients in a minimal disease state after conventional chemotherapy received fractionated total body irradiation and high-dose etoposide and cyclophosphamide, followed by purged autologous bone marrow. A reference sample of 188 patients of similar age, stage, and histology managed at this institution before 1988 was identified for comparison of patient characteristics and outcomes. Compared with reference patients, transplant recipients had a higher tumor burden at diagnosis. With a median follow-up of 6.5 years, the estimated 10-year survival after transplantation was 86%. There was a single lymphoma death yielding a 10-year disease-specific survival of 97%. There were 2 early transplant-related deaths and 2 late acute leukemia deaths. Ten patients relapsed, one with microscopic disease only. High tumor burden at diagnosis and incomplete response to chemotherapy adversely influenced survival in the reference but not in the transplanted patients. The estimated risk of death of 14% and relapse of 30% at 10 years in our transplanted follicular lymphoma patients, the majority of whom had high tumor burdens, compares favorably with our observations in appropriately matched reference patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea/mortalidad , Linfoma Folicular/terapia , Análisis Actuarial , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Estudios de Cohortes , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/normas , Ciclofosfamida/toxicidad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Linfoma Folicular/mortalidad , Masculino , Persona de Mediana Edad , Neoplasia Residual , Prednisona/administración & dosificación , Prednisona/normas , Prednisona/toxicidad , Estudios Prospectivos , Radioterapia Adyuvante , Recurrencia , Inducción de Remisión , Tasa de Supervivencia , Trasplante Autólogo/mortalidad , Vincristina/administración & dosificación , Vincristina/normas , Vincristina/toxicidadRESUMEN
High-dose CBV (cyclophosphamide, carmustine, and etoposide) in combination with autologous HCT achieves survival rates of approximately 50% at 5 years in recurrent or refractory Hodgkin's disease (HD). However, carmustine (BCNU) dose-dependent pulmonary toxicity occurs in 20% to 30% of patients. A decreased incidence of interstitial pneumonitis as well as a possible benefit in efficacy has been reported with lomustine (CCNU) compared to BCNU in the standard dose setting. In a dose-escalation study, we substituted CCNU for BCNU in the CBV regimen for 16 patients with HD (n = 12) or non-Hodgkin's lymphoma (n = 4). Based on the promising results, an additional 47 consecutive patients with HD were treated with the following regimen: CCNU (15 mg/kg) orally on day -6, etoposide (60 mg/kg) intravenously on day -4, and cyclophosphamide (100 mg/kg) intravenously on day -2. Peripheral blood progenitor cells and/or bone marrow were infused on day 0. With a median follow-up for the surviving patients of 3.2 years (range, 0.8-9.9 years), the 3-year overall survival rate was 57% (CI, +/-15%), event-free survival was 52% (CI, +/-14%), and freedom from progression was 68% (CI, +/-14%). There were 21 deaths, 10 due to HD. Six patients died due to respiratory failure. Interstitial pneumonitis occurred in 63% of patients and could not be correlated with prior chest radiotherapy. This regimen demonstrated survival rates similar to those of historical studies that used the CBV regimen. However, the incidence of interstitial pneumonitis was in excess of expected.
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Antineoplásicos Alquilantes/administración & dosificación , Enfermedad de Hodgkin/terapia , Lomustina/administración & dosificación , Trasplante de Células Madre/métodos , Adolescente , Adulto , Anciano , Antineoplásicos Alquilantes/toxicidad , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carmustina/administración & dosificación , Carmustina/toxicidad , Niño , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Etopósido/administración & dosificación , Femenino , Enfermedad de Hodgkin/complicaciones , Humanos , Lomustina/toxicidad , Enfermedades Pulmonares Intersticiales/inducido químicamente , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/terapia , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Terapia Recuperativa/efectos adversos , Terapia Recuperativa/métodos , Terapia Recuperativa/mortalidad , Trasplante de Células Madre/efectos adversos , Trasplante de Células Madre/mortalidad , Tasa de Supervivencia , Equivalencia Terapéutica , Trasplante AutólogoRESUMEN
A diagnostic continuum exists between lymphocyte-predominant Hodgkin's disease, T-cell-rich B-cell lymphoma (TCRBCL), and diffuse large B-cell lymphoma. While TCRBCLs are uncommon, their clinical and morphologic presentation can mimic other Hodgkin's and non-Hodgkin's lymphomas from which they must be distinguished for diagnosis and treatment. We present an unusual case of a 30-year-old man with recurrent TCRBCL arising from lymphocyte-predominant Hodgkin's disease with remarkable response to treatment with the anti-CD20 antibody, rituximab.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Linfoma de Células B/inmunología , Linfoma de Células B/terapia , Linfocitos T/inmunología , Adulto , Anticuerpos Monoclonales de Origen Murino , Humanos , Inmunofenotipificación , Hígado/diagnóstico por imagen , Hígado/efectos de los fármacos , Hígado/patología , Ganglios Linfáticos/patología , Linfoma de Células B/patología , Masculino , Recurrencia Local de Neoplasia , Inducción de Remisión , Rituximab , Bazo/diagnóstico por imagen , Bazo/efectos de los fármacos , Bazo/patología , Linfocitos T/patología , Tomografía Computarizada por Rayos XRESUMEN
Our purpose was to evaluate the outcome and costs of high-dose chemotherapy and autologous peripheral blood progenitor cell (PBPC) transplantation in patients with the inability to mobilize sufficient numbers of PBPCs to allow rapid engraftment after PBPC transplantation. We treated 172 consecutive non-Hodgkin's lymphoma (NHL) patients with cyclophosphamide and granulocyte colony-stimulating factor followed by apheresis to collect PBPCs. The cells were separated on a Percoll gradient and purged with monoclonal antibodies and complement. The patients were categorized as "good" mobilizers if a collection of > or =2 x 10(6) CD34+ cells/kg was obtained (n = 138, 80%) or "poor" mobilizers if <2 x 10(6) CD34+ cells/kg were obtained (n = 34, 20%). With a median follow-up of 3.5 years, there is no statistically significant difference in actuarial event-free survival, overall survival, or relapse for good mobilizers compared with poor mobilizers. However, there was a trend toward increasing nonrelapse, transplantation-related mortality of 11.8% for poor mobilizers versus 3.6% for good mobilizers (P = .08) and early death from all causes including relapse within 120 days (poor 20.6% versus good 8.7%, P = .06). The total cost for bone marrow transplantation-related care was significantly higher, at $140,264 for poor mobilizers versus $80,833 for good mobilizers (P = .0001). The population of patients with NHL who mobilize PBPCs poorly into the circulation have a higher cost for posttransplant support. However, there is no significant difference in relapse, event-free survival, or overall survival for such patients compared with those who mobilize PBPCs easily.
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Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recuento de Células Sanguíneas , California/epidemiología , Carmustina/administración & dosificación , Costos y Análisis de Costo , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Costos de la Atención en Salud , Movilización de Célula Madre Hematopoyética/economía , Trasplante de Células Madre Hematopoyéticas/economía , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/economía , Linfoma no Hodgkin/mortalidad , Masculino , Persona de Mediana Edad , Inducción de Remisión , Resultado del Tratamiento , Irradiación Corporal TotalRESUMEN
A method for the detection of diazepam in horse hair samples by low resolution gas chromatography-mass spectrometry (GC-MS) was developed. Two other techniques, gas chromatography-high-resolution mass spectrometry (GC-HRMS) and high-performance liquid chromatography-atmospheric pressure chemical-ionisation mass spectrometry (HPLC-APCI-MS-MS) were applied on some selected samples. Sample preparation was performed according to a technique previously described for human hair, involving incubation with Sorensen buffer and solvent extraction. Hair samples from different sites such as coat on the neck, coat on the back, mane and tail were collected from two thoroughbreds which had received several dosages of diazepam corresponding to a total dose of 750 mg and 200 mg of diazepam respectively. In the first experiment, by low resolution GC-MS using single ion monitoring, diazepam was detected in the mane for at least 85 d after the last administration. In the second one, using the same method, diazepam was detected in the coat on the neck up to 25 d following the last administration. Low resolution GC-MS data were confirmed by the two other techniques. Furthermore, GC-HRMS even made possible the detection of diazepam up to 38 d after the administration of 200 mg of diazepam.
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Diazepam/análisis , Cabello/química , Hipnóticos y Sedantes/análisis , Animales , Diazepam/química , Caballos , Hipnóticos y Sedantes/química , Espectrometría de Masas/métodosRESUMEN
We conducted a pilot study in 20 patients with high-risk or recurrent/refractory non-Hodgkin's lymphoma (NHL) using high-dose sequential chemotherapy (HDSC) and autologous hematopoietic cell transplantation (AHCT). After cytoreduction with standard salvage therapy, HDSC/AHCT was administered in 4 phases at 2- to 4-week intervals. Phase 1 consisted of cyclophosphamide 7 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) at 10 microg/kg per day and leukapheresis upon recovery from white blood cell nadir. The hematopoietic cell product was enriched by Percoll gradient separation and purged with a B-cell or T-cell monoclonal antibody panel and complement. Phase 2 consisted of methotrexate 8 g/m2 with leucovorin rescue and vincristine 1.4 mg/m2. Phase 3 was etoposide 2 g/m2 with G-CSF 5 microg/kg per day. In phase 4, the preparative regimen of mitoxantrone 60 mg/m2 and melphalan 180 mg/m2 was administered followed by AHCT. The NHL histologies were diffuse large cell, follicular/diffuse mixed, small noncleaved cell, T-cell-rich B-cell, lymphoblastic, and peripheral T cell. The remission status was first partial remission (PR1; n = 1) or beyond first complete remission (post-CR1; n = 19). Of the 20 patients enrolled, 11 proceeded through all 4 phases. Nine were removed from the study after the first or second phase because of progressive disease (n = 5), poor hematopoietic cell mobilization (n = 1), excessive toxicity (n = 2), and chronic active hepatitis C (n = 1). Treatment-related toxicities in the remaining 11 transplant recipients were cardiomyopathy, hemorrhagic cystitis, persistent cytopenias, acute renal failure, abnormal liver function test results, and infectious complications. There were no treatment-related deaths. Eight of the 11 transplant recipients were alive, 6 without disease, at a median follow-up of 2.7 years. The estimated median 2-year event-free survival was 55%, and overall survival was 70%. We conclude that HDSC/AHCT in refractory/recurrent NHL is associated with considerable acute and chronic toxicities. Given the toxicity profile, efficacy data were not sufficiently promising to warrant further study.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Purgación de la Médula Ósea , Movilización de Célula Madre Hematopoyética/efectos adversos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfoma no Hodgkin/tratamiento farmacológico , Acondicionamiento Pretrasplante/efectos adversos , Lesión Renal Aguda/inducido químicamente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades de la Médula Ósea/inducido químicamente , Cardiomiopatías/inducido químicamente , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Cistitis/inducido químicamente , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Esquema de Medicación , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Hemorragia/inducido químicamente , Humanos , Infecciones , Leucovorina/administración & dosificación , Tablas de Vida , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/terapia , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Mitoxantrona/efectos adversos , Proyectos Piloto , Terapia Recuperativa , Análisis de Supervivencia , Tasa de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
PURPOSE: This survey was designed to confirm the prevalence and duration of fatigue in the cancer population and to assess its physical, mental, social, and economic impacts on the lives of patients and caregivers. Patients and Methods. A 25-minute telephone interview was completed with 379 cancer patients having a prior history of chemotherapy. Patients were recruited from a sample of 6, 125 households in the United States identified as having a member with cancer. The median patient age was 62 years, and 79% of respondents were women. Patients reporting fatigue at least a few times a month were asked a series of questions to better describe their fatigue and its impact on quality of life. RESULTS: Seventy-six percent of patients experienced fatigue at least a few days each month during their most recent chemotherapy; 30% experienced fatigue on a daily basis. Ninety-one percent of those who experienced fatigue reported that it prevented a "normal" life, and 88% indicated that fatigue caused an alteration in their daily routine. Fatigue made it more difficult to participate in social activities and perform typical cognitive tasks. Of the 177 patients who were employed, 75% changed their employment status as a result of fatigue. Furthermore, 65% of patients indicated that their fatigue resulted in their caregivers taking at least one day (mean, 4.5 days) off work in a typical month. Physicians were the health care professionals most commonly consulted (79%) to discuss fatigue. Bed rest/ relaxation was the most common treatment recommendation (37%); 40% of patients were not offered any recommendations. CONCLUSIONS: Cancer-related fatigue is common among cancer patients who have received chemotherapy and results in substantial adverse physical, psychosocial, and economic consequences for both patients and caregivers. Given the impact of fatigue, treatment options should be routinely considered in the care of patients with cancer.
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Costo de Enfermedad , Fatiga/etiología , Neoplasias/complicaciones , Calidad de Vida , Adulto , Anciano , Recolección de Datos , Fatiga/economía , Fatiga/epidemiología , Fatiga/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapiaRESUMEN
The use of HDT and AHCT in Hodgkin's disease patients with early relapsed and refractory disease is supported by historical comparisons. In regard to the late relapsed patient or the newly diagnosed high-risk patient, the role AHCT plays would ideally be answered by well-controlled phase 3 trials. A surrogate approach would be the comparison of AHCT data with well-matched historical controls. It is important, however, to be mindful of the changes that have occur red in the therapy of the newly diagnosed and relapsed HD patient (ABVD replacing MOPP regimens) and the impact these changes may or may not have on nonrelapse mortality in the autografted and nonautografted setting. In addition, the incorporation of consistent prognostic factors in any trial design may identify groups of relapsed or refractory and high-risk HD patients who may or may not gain benefit from HDT. The most effective and efficient route to answering these treatment questions is enrollment of patients in well-controlled and well-designed clinical trials.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Análisis Actuarial , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Células Sanguíneas/trasplante , Trasplante de Médula Ósea , Ensayos Clínicos como Asunto , Terapia Combinada , Estudios Cruzados , Supervivencia sin Enfermedad , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Humanos , Persona de Mediana Edad , Pronóstico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Factores de Riesgo , Terapia Recuperativa , Análisis de Supervivencia , Trasplante Autólogo , Resultado del TratamientoRESUMEN
Central nervous system (CNS) involvement by non-Hodgkin's lymphoma (NHL) carries a poor patient prognosis whether it occurs as a primary site of disease or secondarily in patients with systemic disease. In a group of 481 patients undergoing high-dose therapy with hematopoietic cell transplantation (HCT) for NHL, 15 patients (3.1%) were identified with CNS involvement. Two patients had primary CNS lymphoma, and 13 had secondary disease. All patients received intrathecal chemotherapy, and 13 received CNS radiotherapy before transplantation. Fourteen patients received systemic chemotherapy. At the time of transplantation, both patients with primary CNS lymphoma and 8 patients with secondary disease had achieved a complete response, 3 patients had achieved a partial response, 1 had failed induction therapy, and 1 had progression of CNS disease before high-dose therapy. Fourteen patients received carmustine, etoposide, and cyclophosphamide as the preparative regimen, and 1 patient received fractionated total body irradiation instead of carmustine. The 2 patients with primary CNS lymphoma were alive and free of disease, 1 at 1,085 days after HCT and 1 at 3,704 days after HCT. The actuarial 5-year event-free survival (EFS) was 46% +/- 26%, and overall survival (OS) was 41% +/- 28%. The median EFS and OS were 2.2 and 1.5 years, respectively. Three patients experienced symptomatic memory loss or intellectual decline after therapy, 1 patient developed paraplegia, and 1 patient had a thrombotic stroke 20 months after HCT. Despite treatment-related toxicities, 7 patients responding to quality-of-life questions at approximately 1 year after HCT gave their overall quality of life a median rating of 9 out of a possible 10 (range, 6-10). High-dose therapy with autologous HCT can produce extended EFS in patients with secondary CNS lymphoma and possibly in those with primary CNS NHL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/terapia , Sistema Nervioso Central/patología , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin/terapia , Análisis Actuarial , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Purgación de la Médula Ósea , Carmustina/administración & dosificación , Carmustina/efectos adversos , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/radioterapia , Trastornos del Conocimiento/etiología , Terapia Combinada , Irradiación Craneana , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/radioterapia , Masculino , Persona de Mediana Edad , Mielitis Transversa/etiología , Invasividad Neoplásica , Calidad de Vida , Traumatismos por Radiación/etiología , Análisis de Supervivencia , Tasa de Supervivencia , Acondicionamiento Pretrasplante/efectos adversos , Resultado del Tratamiento , Irradiación Corporal TotalRESUMEN
Given the successful treatment for most patients with Hodgkin's lymphoma, efforts have been directed primarily toward improving outcomes for the minority of patients with poor prognosis or relapsed disease or reducing the late effects of therapy for long-term survivors. Recently, a simple and clinically useful prognostic scoring system was developed for patients with advanced disease. This system allows better risk assessment for individual patients and more uniformity among patients participating in clinical trials. In addition, trials using newer chemotherapeutic regimens such as Stanford V or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are maturing with promising results. Other studies are helping to define the role of high-dose therapy for patients with Hodgkin's lymphoma, although biologic treatments such as cellular or antibody-based therapies are still in early phases of development. Lastly, positron emission tomographic scanning is emerging as a useful tool in staging and following Hodgkin's lymphoma.
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Enfermedad de Hodgkin/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/radioterapia , Humanos , Inmunoterapia , Masculino , Estudios Multicéntricos como Asunto , Estadificación de Neoplasias , Pronóstico , Radioterapia/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Inducción de Remisión , Terapia Recuperativa , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tomografía Computarizada de EmisiónRESUMEN
BACKGROUND: Oncologic literature cites many different definitions of critical response measurements. PATIENTS AND METHODS: Response criteria (RC) for non-Hodgkin's lymphoma (NHL) were developed by lymphoma experts, endorsed by international lymphoma clinicians, and applied to a 166-patient rituximab (Rituxan, MabThera) trial by a third-party, blinded panel of NHL experts (LEXCOR). Retrospectively, we analyzed this data using variations of the original RC and comparing with recently published RC. RESULTS: The definition of a 'normal' lymph node affected the complete response (CR) rate (< or = 1.0 x 1.0 cm, 6%; < or = 1.5 x 1.5 cm, 18%; < or = 2.0 x 2.0 cm, 28%); overall response rate (ORR) was not affected. CR rates increased progressively without > or = 28 days response confirmation: 12% vs. 6% (< or = 1.0 x 1.0 cm), 26% vs. 18% (< or = 1.5 x 1.5 cm), and 36% vs. 28% (< or = 2.0 x 2.0 cm). CR rate and duration of response (DR) were unaffected when only the six largest, rather than all lesions, were measured. When the new RC were applied, CR rate (32%) was higher and DR (13.9 months) and time to progression (15.6 months) were shorter in complete responders. CONCLUSIONS: Standard RC must be consistently and rigorously applied for accurate comparisons between studies.