RESUMEN
Limited data exist to describe the clinical features and outcomes for elderly patients with follicular lymphoma (FL). The Follicular Lymphoma Analysis of Surrogacy Hypothesis (FLASH) group performed a prospectively planned pooled analysis of individual patient data from first-line randomized controlled trials (RCTs) and examined associations between age (≤70 vs >70 years), clinical characteristics, and FL outcomes. We identified 18 multicenter clinical RCTs in the FLASH database that enrolled elderly patients (>70 years). Primary end points were early disease outcomes, CR24 and CR30, and progression-free survival (PFS) at 24 months (PFS24). Secondary end points were PFS and overall survival (OS). We identified 5922 previously untreated FL patients from 18 RCTs. Patients age >70 years (vs ≤70 years) more commonly had elevated lactate dehydrogenase, hemoglobin <12 g/dL, ECOG PS ≥2, and elevated ß2-microglobulin. Median follow-up was 5.6 years. Patients >70 years did not differ from patients ≤70 years in rates of CR24, CR30, or PFS24. With a median OS of 14.6 years for all patients, median OS was 7.4 and 15.7 years for patients >70 and ≤70 years of age, respectively (hazard ratio = 2.35; 95% confidence interval = 2.03-2.73; P < .001). Age >70 years was a significant predictor of OS and PFS due to higher rates of death without progression, but not PFS24, CR24, or CR30. FL patients >70 years treated on trials have similar early disease outcomes to younger patients. There is no disease-specific outcome difference between age groups. Age alone should not disqualify patients from standard treatments or RCTs.
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Linfoma Folicular , Anciano , Humanos , Linfoma Folicular/tratamiento farmacológico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como AsuntoAsunto(s)
Fluorodesoxiglucosa F18 , Histiocitos/patología , Linfoma/tratamiento farmacológico , Linfoma/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Sarcoidosis/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Femenino , Humanos , Inmunohistoquímica , Linfoma/terapia , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Prednisolona/efectos adversos , Prednisolona/uso terapéutico , Vincristina/efectos adversos , Vincristina/uso terapéuticoRESUMEN
Pegylated liposomal doxorubicin (PLD) can be administered for prolonged periods with minimal toxicity. The risk of cutaneous squamous cell carcinoma (SCC) with this therapy has not been reported. We describe cutaneous SCC of the plantar foot in two patients exposed to high doses of PLD. A 50-year-old man with angiosarcoma received a total PLD dose of 1350 mg/m2 and developed cutaneous SCC of bilateral plantar feet. A 45-year-old woman with cutaneous T-cell lymphoma was treated with a total PLD dose of 1142 mg/m2 with subsequent diagnosis of cutaneous SCC of the right plantar foot. No risk factors for SCC of the plantar foot were identified in either patient. Cutaneous SCC is likely an unreported side effect of prolonged exposure to PLD. An extended duration of hand-foot syndrome from other anti-cancer drugs may also share this risk. Regular complete skin examination with early intervention for suspicious lesions is indicated in this patient population.
Asunto(s)
Carcinoma de Células Escamosas/inducido químicamente , Doxorrubicina/análogos & derivados , Síndrome Mano-Pie/etiología , Neoplasias Cutáneas/inducido químicamente , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patología , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Femenino , Enfermedades del Pie/inducido químicamente , Enfermedades del Pie/diagnóstico , Enfermedades del Pie/patología , Hemangiosarcoma/tratamiento farmacológico , Humanos , Linfoma Cutáneo de Células T/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patologíaRESUMEN
BACKGROUND: Colon and rectal lymphomas are rare and can occur in the context of posttransplant lymphoproliferative disorder. Evidence-based management guidelines are lacking. OBJECTIVE: The purpose of this study was to characterize the presentation, diagnosis, and management of colorectal lymphoma and to identify differences within the transplant population. DESIGN: This was a retrospective review of patients evaluated for colorectal lymphoma between 2000 and 2017. Patients were identified through clinical note queries. SETTINGS: Four hospitals within a single health system were included. PATIENTS: Fifty-two patients (64% men; mean age = 64 y; range, 26-91 y) were identified. No patient had <3 months of follow-up. Eight patients (15%) had posttransplant lymphoproliferative disorder. MAIN OUTCOME MEASURES: Overall survival, recurrence, and complications in treatment pathway were measured. RESULTS: Most common presentations were rectal bleeding (27%), abdominal pain (23%), and diarrhea (23%). The most common location was the cecum (62%). Most frequent histologies were diffuse large B-cell lymphoma (48%) and mantle cell lymphoma (25%). Posttransplant lymphoproliferative disorder occurred in the cecum (n = 4) and rectum (n = 4). Twenty patients (38%) were managed with chemotherapy; 25 patients (48%) underwent primary resection. Mass lesions had a higher risk of urgent surgical resection (35% vs 8%; p = 0.017). Three patients (15%) treated with chemotherapy presented with perforation requiring emergency surgery. Overall survival was 77 months (range, 25-180 mo). Patients with cecal involvement had longer overall survival (96 vs 26 mo; p = 0.038); immunosuppressed patients had shorter survival (16 vs 96 mo; p = 0.006). Survival in patients treated with surgical management versus chemotherapy was similar (67 vs 105 mo; p = 0.62). LIMITATIONS: This was a retrospective chart review, with data limited by the contents of the medical chart. This was a small sample size. CONCLUSIONS: Colorectal lymphoma is rare, with variable treatment approaches. Patients with noncecal involvement and chronic immunosuppression had worse overall survival. Patients with mass lesions, particularly cecal masses, are at higher risk to require urgent intervention, and primary resection should be considered. See Video Abstract at http://links.lww.com/DCR/A929.
Asunto(s)
Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/terapia , Linfoma/diagnóstico , Linfoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Terapia Combinada , Femenino , Humanos , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: Testicular cancer survivors who have received platinum-based chemotherapy are at risk for premature cardiovascular disease. The etiology of this risk is not well understood. This pilot study explores the impact of platinum-based chemotherapy on endothelial function. METHODS: Testicular cancer survivors <30 years old at the time of diagnosis who received platinum-based chemotherapy between 2002 and 2012, as well as 17 similarly aged male controls, were identified. Consented subjects underwent vascular assessment using the HDI/PulseWave CR-2000 Cardiovascular Profiling System and the Endo-PAT2000 system. Biomarkers and functional test markers were compared among cases, controls, and a group of historical controls using two sided two-sampled t-tests and Wilcoxon rank-sum tests. RESULTS: Thirteen survivors with a median age of 30.2 years and body mass index of 27.3 were enrolled, along with 17 healthy controls with a median age of 27.1 years and body mass index of 24.8. Median time from chemotherapy was 4.7 (range: 0.8-14) years. There was no statistical difference in reactive hyperemia peripheral arterial tonometry ratio between cases and controls (p = 0.574). There was no statistical difference in small or large artery elasticity between cases and controls (p = 0.086) or between cases and historical controls (p = 0.729). There was also no statistical difference in the blood levels of circulating endothelial cells, von Willebrand factor, and vascular cell adhesion molecules. There was a trend toward increased metabolic syndrome in cases (15%) as compared to recruited controls (6%), though this difference was not statistically significant (p = 0.565). CONCLUSION: Testicular cancer survivors have no clinically significant difference in endothelial function compared to controls 4 years after the completion of chemotherapy. Further research is needed to explore the secondary modifiable causes that may contribute to the risk of premature cardiovascular disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivientes de Cáncer , Enfermedades Cardiovasculares/inducido químicamente , Compuestos Organometálicos/efectos adversos , Compuestos de Platino/efectos adversos , Neoplasias Testiculares/tratamiento farmacológico , Rigidez Vascular/efectos de los fármacos , Adulto , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Estudios Transversales , Diagnóstico Precoz , Elasticidad , Humanos , Masculino , Proyectos Piloto , Valor Predictivo de las Pruebas , Factores de Riesgo , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/epidemiología , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Purpose Follicular lymphoma (FL) is an indolent cancer, with effective but rarely curative treatment options. As a standard study end point for first-line FL therapy, progression-free survival (PFS) requires extended follow-up (median PFS, > 7 years). To provide patients with earlier access to newer therapies, an earlier end point to expedite clinical trials is needed. Our objective was to formally assess the complete response rate at 30 months (CR30) after initiation of induction therapy as a potential surrogate end point for PFS in first-line FL therapy. Patients and Methods We analyzed individual patient data from 13 randomized multicenter trials of induction and maintenance regimens in first-line FL therapy published after 1990 and with sufficient data to evaluate whether CR30 could predict treatment effects on PFS. Correlation of the CR30 odds ratio with the PFS hazard ratio was evaluated by both linear regression (R2WLS) and bivariate copula (R2Copula) models. Prespecified criteria for surrogacy required either R2WLS or R2Copula ≥ 0.80, with a lower-bound 95% CI > 0.60. Results Data from eight induction and five maintenance randomized trials in 3,837 evaluable patients were analyzed. The prespecified surrogacy threshold was met, with an R2WLS of 0.88 (95% CI, 0.77 to 0.96) and an R2Copula of 0.86 (95% CI, 0.72 to 1.00). Multiple sensitivity and supplemental analyses supported the robustness of the findings. A minimum 11% absolute improvement in CR30 from a 50% control rate predicted a significant treatment effect on PFS (hazard ratio, 0.69). Conclusion This large, prospective, pooled analysis of randomized chemotherapy, immunotherapy, and chemoimmunotherapy trials demonstrates that CR30 is a surrogate end point for PFS in first-line FL treatment trials. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before PFS results are mature.
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Quimioterapia de Inducción/métodos , Linfoma Folicular/tratamiento farmacológico , Quimioterapia de Mantención/métodos , Inducción de Remisión , Adulto , Anciano , Anciano de 80 o más Años , Ensayos Clínicos Fase III como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Modelos de Riesgos Proporcionales , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Tiempo , Adulto JovenRESUMEN
Patterns of myeloid growth factor (GF) usage and febrile neutropenia (FN) were examined in patients >60 years of age with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) enrolled on CALGB 9793/ECOG-SWOG 4494, receiving initial therapy with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or rituximab + CHOP (R-CHOP). Myeloid GFs were administered to 256/520 (49%) patients. Indications for use were: prevent dose reduction/dose delay (81%, 207/256); treat FN or non-febrile neutropenia (NFN) (19%, 48/256). One or more FN episodes occurred in 41% (212/520) of patients, with FN most often in cycle 1 (38% of episodes). In multivariate analysis, risk factors for FN included age >65 years (odds ratio (OR) = 2.6, 95% CI: [1.4, 4.9]) and anemia (hemoglobin <12 g/dl) (OR =2.2, 95% confidence intervals (CI): [1.4, 3.5]. Myeloid GF use was common in this older DLBCL population receiving CHOP-based therapy, as was FN, especially during cycle one. Risk factors predictive for FN should be used prospectively to identify patients for whom myeloid GFs are best utilized.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Factores Estimulantes de Colonias/uso terapéutico , Neutropenia Febril/tratamiento farmacológico , Neutropenia Febril/etiología , Linfoma de Células B Grandes Difuso/complicaciones , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factores Estimulantes de Colonias/administración & dosificación , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Neutropenia Febril/diagnóstico , Neutropenia Febril/epidemiología , Femenino , Humanos , Incidencia , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/efectos adversos , Prednisona/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Rituximab , Factores de Tiempo , Resultado del Tratamiento , Vincristina/efectos adversos , Vincristina/uso terapéuticoRESUMEN
We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline-based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c-statistic = 0.671) in the validation dataset compared to the IPI (c-statistic = 0.649) or the NCCN-IPI (c-statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12-88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps.
Asunto(s)
Linfoma de Células B Grandes Difuso/mortalidad , Modelos Estadísticos , Medicina de Precisión , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunoterapia/métodos , Estimación de Kaplan-Meier , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
The correlation of rheumatoid arthritis and lymphoma-and more generally, autoimmune disease and malignancy-has long been observed. Here, we present the case of a woman with rheumatoid arthritis who developed lymphoma limited to her hands.
Asunto(s)
Artritis Reumatoide/epidemiología , Mano , Linfoma de Células B Grandes Difuso/epidemiología , Neoplasias de los Tejidos Blandos/epidemiología , Anciano , Antirreumáticos/uso terapéutico , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Fraccionamiento de la Dosis de Radiación , Femenino , Mano/diagnóstico por imagen , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/radioterapia , Metotrexato/uso terapéutico , Tomografía de Emisión de Positrones , Radiografía , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/radioterapiaRESUMEN
BACKGROUND: Vascular-related toxicities have been reported among survivors of Hodgkin lymphoma (HL), but their genesis is not well understood. PROCEDURE: Fasting blood samples from 25 previously irradiated HL survivors were analyzed for biomarkers that can reveal underlying inflammation and/or endothelial cell activation: high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein (HDL), apolipoprotein ß, lipoprotein (a), fibrinogen, circulating endothelial cells (CECs), and vascular cell adhesion molecule-1 (VCAM-1) expression. Values were compared to subjects in the Coronary Artery Risk Development in Young Adults (CARDIA) study. CECs and VCAM-1 were compared to healthy controls. RESULTS: Survivors (76% male), median age 17.6 years (5-33) at diagnosis, 33.0 years (19-55) at follow-up, included stages IA (n = 6), IIA (n = 10), IIB (n = 2), IIIA (n = 4), and IVA (n = 3) patients. Twenty-four received at least chest radiation therapy (RT) (median dose 3,150 cGy; range: 175-4,650 cGy), one received neck only; 14 (56%) had a history of anthracycline exposure (median dose: 124 mg/m(2) range: 63-200 mg/m2). Compared to CARDIA subjects, mean hsCRP (3.0 mg/L ± 2.0 vs. 1.6 ± 1.9), total cholesterol (194.1 mg/dl ± 33.2 vs. 179.4 ± 32.9), lipoprotein (a) (34.2 mg/dl ± 17.5 vs. 13.8 ± 17.5), and fibrinogen (342.0 mg/dl ± 49.1 vs. 252.6 ± 48.4) were significantly elevated. CECs (2.3 cells/ml ± 1.5 vs. 0.34 ± 1.4) were significantly elevated compared to controls. No difference in VCAM-1 expression (51.1% ± 36.8 vs. 42.3 ± 35.6) was detected. CONCLUSION: HL survivors exposed to RT have evidence of vascular inflammation, dyslipidemia, and injury suggestive of early atherogenesis.
Asunto(s)
Biomarcadores/sangre , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/mortalidad , Sobrevivientes , Enfermedades Vasculares/etiología , Enfermedades Vasculares/mortalidad , Adolescente , Adulto , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Niño , Preescolar , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Fibrinógeno/metabolismo , Estudios de Seguimiento , Enfermedad de Hodgkin/radioterapia , Humanos , Inflamación/sangre , Inflamación/etiología , Inflamación/mortalidad , Lipoproteína(a)/sangre , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proyectos Piloto , Dosificación Radioterapéutica , Tasa de Supervivencia , Triglicéridos/sangre , Molécula 1 de Adhesión Celular Vascular/sangre , Enfermedades Vasculares/sangre , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Castleman disease can occur in association with autoimmune connective tissue disease and confound the clinical picture, resulting in delayed diagnosis and suboptimal treatment. This review focuses on the intersection of Castleman disease and autoimmunity with an emphasis on shared pathology and mutually beneficial treatments. RECENT FINDINGS: Targeting CD-20, interleukin-6, and the nuclear factor-κB pathway has shown promise in achieving long-term remission in patients with Castleman disease and associated autoimmune features. SUMMARY: Advances in understanding of pathogenic cell types and cytokines in Castleman disease have allowed the development of targeted therapies successful in the treatment of both Castleman disease and associated autoimmune disease.
Asunto(s)
Enfermedades Autoinmunes/complicaciones , Enfermedad de Castleman/complicaciones , Enfermedades Autoinmunes/patología , Enfermedades Autoinmunes/terapia , Enfermedad de Castleman/patología , Enfermedad de Castleman/terapia , HumanosRESUMEN
Few studies have examined the quality of life (QOL) in survivors of non-Hodgkin lymphoma (NHL). A total of 109 patients with NHL (58 aggressive [AGG], 51 indolent [IND]) completed two health-related QOL assessments using the Medical Outcomes Study 36-Item Short-Form Healthy Survey (MOS SF-36) and the Functional Assessment in Cancer Therapy - Fatigue (FACT-F). Scores between IND and AGG were compared using a two-sample t-test. Multiple linear regression was performed to account for any potentially explanatory variables. Overall, 70.6% had received chemotherapy and 55% had received immunotherapy. Some 17.6% of the IND group had received no therapy. The overall physical and mental component QOL scores of the SF-36 did not differ between survivors. Physical function in survivors of IND was significantly better when compared with that of AGG NHL. Our study reports a similar overall QOL between survivors of IND and AGG NHL. Physical function, however, may be more impaired in survivors of AGG NHL.
Asunto(s)
Linfoma no Hodgkin/psicología , Calidad de Vida/psicología , Encuestas y Cuestionarios , Sobrevivientes/psicología , Adulto , Anciano , Fatiga/psicología , Femenino , Encuestas Epidemiológicas , Humanos , Modelos Lineales , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Análisis MultivarianteRESUMEN
Anti-B4-blocked ricin (anti-B4-bR) is a potent immunotoxin directed against the CD19 antigen. Previous phase I and II studies suggested a possible role for anti-B4-bR as consolidation after high-dose chemotherapy and autologous stem cell transplant. Cancer and Leukemia Group B (CALGB) 9254 is a phase III study which randomized 157 patients with B-cell lymphoma in complete remission following autologous transplant to treatment with anti-B4-bR or observation. With a median follow-up time for patients of 5.8 years, the median event-free survival for protocol treatment and observation are 2.1 and 2.9 years, respectively (p = 0.275). The median overall survival for treatment and observation are 6.1 years and not reached, respectively (p = 0.063). Therefore, no differences were found in event-free survival and overall survival between protocol treatment and observation, although there was a trend toward improved survival with observation. These data fail to support a role for anti-B4-bR as consolidative therapy after bone marrow transplant in patients with B-cell lymphoma.
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Adyuvantes Inmunológicos/uso terapéutico , Trasplante de Médula Ósea , Inmunoconjugados/uso terapéutico , Linfoma de Células B/terapia , Ricina/uso terapéutico , Trasplante Autólogo , Adyuvantes Inmunológicos/efectos adversos , Adyuvantes Inmunológicos/farmacocinética , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante , Femenino , Humanos , Inmunoconjugados/efectos adversos , Inmunoconjugados/farmacocinética , Linfoma de Células B/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Ricina/efectos adversos , Ricina/farmacocinética , Análisis de Supervivencia , Acondicionamiento Pretrasplante , Resultado del Tratamiento , Adulto JovenRESUMEN
To assess if immunochemotherapy influenced the prognostic value of IPI in elderly diffuse large B-cell lymphoma (DLBCL) patients, we evaluated the performance of the standard International Prognostic Index (IPI) and following modifications: age adjusted (AA)-IPI, revised (R)-IPI, and an elderly IPI with age cut-off 70 years (E-IPI) in patients > 60 years treated with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). In 267 patients, by IPI/AA-IPI 60% were high-intermediate, 53% high and 12% low risk. With R-IPI, 60% were poor risk and none very good risk. Using E-IPI, 45% were high-intermediate/high risk and 27% low risk. No differences in outcome were seen in the low/low-intermediate groups with IPI/AA-IPI. For E-IPI, failure-free survival (FFS) and overall survival (OS) were significantly different for low/low-intermediate groups. No differences were detected in the four indices with model fit/discrimination measures; however, E-IPI ranked highest. For elderly R-CHOP treated patients, distribution of IPI/AA-IPI skewed toward high/high-intermediate risk with no differences in FFS/OS between low/low-intermediate risk. In contrast, with E-IPI, more are classified as low risk with significant differences in FFS/OS for low-intermediate compared to low risk. The R-IPI does not identify a very good risk group, thus minimizing its utility in this population. The prognostic discrimination provided by the E-IPI for low and low-intermediate elderly DLBCL patients needs validation by other datasets.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Indicadores de Salud , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Esquema de Medicación , Métodos Epidemiológicos , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Pronóstico , Rituximab , Resultado del Tratamiento , Vincristina/administración & dosificación , Vincristina/uso terapéuticoRESUMEN
Doxorubicin (DOX), despite causing cardiac toxicity, is an anthracycline chemotherapeutic agent that plays an important role in the treatment of breast cancer. Angiotensin-converting enzyme inhibitors (ACE-I) may protect against cardiac toxicity in patients receiving DOX chemotherapy. A total of 143 patients receiving DOX at the Masonic Comprehensive Cancer Clinic, University of Minnesota, who had two or more multigated blood pool imaging (MUGA) scans or echocardiograms performed between 2004 and 2007 were identified and reviewed. Patients with a 10% absolute drop in their ejection fraction (EF) or more to below 55% were identified and compared with those that did not have a 10% decline in EF. Impact of patient variables and the use of concurrent medications on EF drop were evaluated using logistic regression. Median age was 52 years old. 85 (60%) were female. Cancer diagnosis was breast (n = 26), lymphoma (n = 92), and other (n = 25). In spite of a similar baseline EF in all the patients, 22/142 (15%) patients had a significant drop in EF during DOX chemotherapy. Adjusting for age, the odds ratio of EF drop associated with the use of ACE-I is 0.267 (P = 0.0940), suggesting that ACE-I has a protective effect. Cumulative DOX dose, the use of beta-blockers, or aspirin did not appear to be predictive or protective. Although not statistically significant, this study suggests that the use of ACE-I when given with DOX chemotherapy protects against DOX chemotherapy and warrants further investigation.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antibióticos Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/efectos adversos , Cardiopatías/prevención & control , Linfoma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Niño , Femenino , Cardiopatías/inducido químicamente , Cardiopatías/diagnóstico por imagen , Cardiopatías/fisiopatología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Minnesota , Oportunidad Relativa , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Volumen Sistólico/efectos de los fármacos , Ultrasonografía , Adulto JovenRESUMEN
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of transplantation. We examined the role of positron emission tomography (PET) scanning in PTLD. METHODS: All patients treated for PTLD from 2001-2006 who also underwent PET scans were reviewed. RESULTS: Nineteen PTLD patients were included. Seventeen patients had PET scans for staging at diagnosis. Of these, two patients with primary central nervous system lymphoma and one patient with only bone marrow involvement after complete surgical resection of a bowel lesion had no abnormalities on CT or PET scan. The remaining patients had measurable, extracranial disease by CT scan and PET scan. The median maximum standard uptake value was 8.2 (range 3-30). Thirteen patients had a PET scan following treatment. Eleven of 13 patients had a complete response (CR). Two of 13 patients had persistent disease following therapy; in one of these patients, relapsed disease was documented by PET scan alone. Of the 11 patients with CR, three patients relapsed shortly thereafter. In each case, at the time of relapse, the PET scan confirmed recurrent disease regardless of histopathologic subtype. CONCLUSIONS: PET scans may have a role in the staging and follow-up of patients with PTLD. Additional prospective studies are warranted.
Asunto(s)
Trastornos Linfoproliferativos/diagnóstico por imagen , Trasplante de Órganos/efectos adversos , Tomografía de Emisión de Positrones/métodos , Adolescente , Adulto , Anciano , Biopsia , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Citometría de Flujo , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Trastornos Linfoproliferativos/etiología , Trastornos Linfoproliferativos/patología , Masculino , Mediastino , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
PURPOSE: To evaluate the efficacy and toxicity of the topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), in patients with relapsed lymphoma and to correlate 9-AC plasma concentrations with response and toxicity. METHODS: Eligible patients had relapsed Hodgkin lymphoma (HL) treated with one or two prior regimens, low grade non-Hodgkin's lymphoma (NHL) treated with one or two prior regimens, or aggressive NHL treated with one prior regimen. The first nine patients received 9-AC dimethylacetamide 0.85 mg/m(2) per day intravenously over 72 h every 2 weeks and the remaining 27 patients received 9-AC/colloidal dispersion 1.1 mg/m(2) per day. Patients received a minimum of three cycles unless progression or intolerable toxicity occurred. Responding patients received two cycles past best response with a minimum of six cycles. RESULTS: CALGB 9551 accrued 37 patients from April 1996 through October 2000; one patient with HD, 18 patients with indolent lymphoma, and 17 patients with aggressive lymphoma. The overall response rate was 17%, with response rates of 11% (2 partial responses) in patients with indolent histologies and 23% (1 complete response, 3 partial responses) in patients with aggressive histologies. The patient with HD did not respond. Response rates were similar for both drug formulations. The median remission duration for the six responders was 6.5 months, with one remission lasting longer than 12 months. Significant grade 3 and 4 toxicities included neutropenia (66%), anemia (31%), and thrombocytopenia (36%), with 20% of patients experiencing grade 3 or 4 infection. No treatment related deaths occurred. Steady state serum concentrations did not correlate with patient response or toxicity. CONCLUSION: Single agent 9-AC has modest activity in aggressive non-Hodgkin's lymphomas.
Asunto(s)
Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Enfermedad de Hodgkin/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Linfoma Folicular/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Camptotecina/sangre , Camptotecina/farmacocinética , Camptotecina/uso terapéutico , Resistencia a Antineoplásicos , Femenino , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/patología , Humanos , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/patología , Linfoma Folicular/sangre , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/patología , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pronóstico , Terapia Recuperativa , Tasa de SupervivenciaRESUMEN
The effect of rituximab on malignant B cells and normal circulating B cells has been previously studied. In contrast, data on the degree of depletion of nonneoplastic B cells induced by rituximab in lymph nodes and spleen is limited. For this purpose, clinical charts, autopsy records, lymph node and spleen sections, and immunoperoxidase stains were reviewed from 10 patients who had received 1 to 40 doses of rituximab before death. The percentage of nonneoplastic B cells was lower in the lymph node and spleen in rituximab-treated patients when compared with cyclophosphamide, doxorubicin, vincristine, and prednisone-treated patients and patients without lymphoma. The effect of rituximab on nonneoplastic B cells was observed as soon as 1 month after administration and with as few as 3 doses. Reappearance of normal numbers of B cells was not observed 1 to 12 months after the last dose of rituximab was administered. We conclude that rituximab induces prompt, consistent, profound, and prolonged depletion of B lymphocyte populations in human lymphoid tissue.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Linfocitos B/efectos de los fármacos , Ganglios Linfáticos/efectos de los fármacos , Bazo/efectos de los fármacos , Adolescente , Adulto , Anticuerpos Monoclonales de Origen Murino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Autopsia , Niño , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Inmunohistoquímica , Linfoma de Células B/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisona/uso terapéutico , Rituximab , Vincristina/uso terapéuticoRESUMEN
Toxic leukoencephalopathy syndromes are rare disorders of cerebral injury characterized by changes in the white matter and accompanying neurologic dysfunction. They have been reported in association with a variety of clinical etiologies, most commonly including severe hypertension, cranial irradiation, and environmental toxins. However, they have also been described in conjunction with immunosuppressive and chemotherapeutic agents. There has been one case of fatal leukoencephalopathy reported following CHOP chemotherapy for non-Hodgkin lymphoma. We report a second case of fatal necrotizing leukoencephalopathy following the administration of CHOP chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Encefalopatías/etiología , Encefalopatías/patología , Linfoma no Hodgkin/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Corteza Cerebral/patología , Terapia Combinada , Ciclofosfamida/efectos adversos , Ciclofosfamida/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/uso terapéutico , Humanos , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/radioterapia , Masculino , Prednisona/efectos adversos , Prednisona/uso terapéutico , Vincristina/efectos adversos , Vincristina/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: Castleman disease was initially described over 50 years ago as a benign localized mass of lymph nodes found primarily in the mediastinum of asymptomatic patients. Subsequently, additional types were recognized that extend the spectrum of this heterogeneous group of diseases. Optimal standard therapies have not been established. Currently, most patients receive treatments derived from past experience with non-Hodgkin lymphoma that are not altogether satisfactory. RECENT FINDINGS: Advances in understanding the biological basis of Castleman disease have provided new targets for therapeutic exploitation. Recognition of the role of interleukin-6 in disease perpetuation has led to the use of an antihuman interleukin-6 receptor monoclonal antibody, tocilizumab. Rituximab, an anti-CD20 monoclonal antibody, targets CD20-positive B lymphocytes, a prominent component of this disorder. Human herpes virus-8 and angiogenesis, both involved in the pathogenesis of Castleman disease, may provide additional unique therapeutic opportunities. SUMMARY: Rational approaches to the treatment of Castleman disease have begun to have an impact on disease management; however, the role of these new agents remains to be established. As the complexity of Castleman disease is more fully understood, additional targets for new innovative therapies undoubtedly will be identified.