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1.
Dis Colon Rectum ; 62(6): 694-702, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30870226

RESUMO

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.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Linfoma/diagnóstico , Linfoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Terapia Combinada , Feminino , Humanos , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
2.
Am J Hematol ; 91(2): 179-84, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26492520

RESUMO

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.


Assuntos
Linfoma Difuso de Grandes Células B/mortalidade , Modelos Estatísticos , Medicina de Precisão , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
4.
Curr Opin Rheumatol ; 24(1): 76-83, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22157415

RESUMO

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.


Assuntos
Doenças Autoimunes/complicações , Hiperplasia do Linfonodo Gigante/complicações , Doenças Autoimunes/patologia , Doenças Autoimunes/terapia , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/terapia , Humanos
5.
Pediatr Blood Cancer ; 59(2): 285-9, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22457206

RESUMO

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.


Assuntos
Biomarcadores/sangue , Doença de Hodgkin/complicações , Doença de Hodgkin/mortalidade , Sobreviventes , Doenças Vasculares/etiologia , Doenças Vasculares/mortalidade , Adolescente , Adulto , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Fibrinogênio/metabolismo , Seguimentos , Doença de Hodgkin/radioterapia , Humanos , Inflamação/sangue , Inflamação/etiologia , Inflamação/mortalidade , Lipoproteína(a)/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Dosagem Radioterapêutica , Taxa de Sobrevida , Triglicerídeos/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Doenças Vasculares/sangue , Adulto Jovem
6.
Blood Adv ; 5(6): 1737-1745, 2021 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-33749762

RESUMO

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.


Assuntos
Linfoma Folicular , Idoso , Humanos , Linfoma Folicular/tratamento farmacológico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Br J Haematol ; 151(2): 143-51, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20735398

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Indicadores Básicos de Saúde , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Esquema de Medicação , Métodos Epidemiológicos , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/patologia , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Prognóstico , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/uso terapêutico
8.
Breast Cancer Res Treat ; 122(2): 585-90, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20058065

RESUMO

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.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/efeitos adversos , Cardiopatias/prevenção & controle , Linfoma/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Feminino , Cardiopatias/induzido quimicamente , Cardiopatias/diagnóstico por imagem , Cardiopatias/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Minnesota , Razão de Chances , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico/efeitos dos fármacos , Ultrassonografia , Adulto Jovem
9.
Clin Transplant ; 23(6): 794-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20447185

RESUMO

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.


Assuntos
Transtornos Linfoproliferativos/diagnóstico por imagem , Transplante de Órgãos/efeitos adversos , Tomografia por Emissão de Pósitrons/métodos , Adolescente , Adulto , Idoso , Biópsia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Fluordesoxiglucose F18 , Seguimentos , Humanos , Imuno-Histoquímica , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/patologia , Masculino , Mediastino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto Jovem
10.
Cancer Chemother Pharmacol ; 84(1): 217-221, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31041511

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas/induzido quimicamente , Doxorrubicina/análogos & derivados , Síndrome Mão-Pé/etiologia , Neoplasias Cutâneas/induzido quimicamente , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Doenças do Pé/induzido quimicamente , Doenças do Pé/diagnóstico , Doenças do Pé/patologia , Hemangiossarcoma/tratamento farmacológico , Humanos , Linfoma Cutâneo de Células T/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia
11.
Leuk Res ; 32(10): 1611-4, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18378307

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encefalopatias/etiologia , Encefalopatias/patologia , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Córtex Cerebral/patologia , Terapia Combinada , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Humanos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/radioterapia , Masculino , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico
12.
Am J Clin Pathol ; 130(4): 604-12, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18794054

RESUMO

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.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Linfócitos B/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Baço/efeitos dos fármacos , Adolescente , Adulto , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Autopsia , Criança , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Linfoma de Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Rituximab , Vincristina/uso terapêutico
13.
Vasc Health Risk Manag ; 14: 205-211, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30237722

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Sobreviventes de Câncer , Doenças Cardiovasculares/induzido quimicamente , Compostos Organometálicos/efeitos adversos , Compostos de Platina/efeitos adversos , Neoplasias Testiculares/tratamento farmacológico , Rigidez Vascular/efeitos dos fármacos , Adulto , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Diagnóstico Precoce , Elasticidade , Humanos , Masculino , Projetos Piloto , Valor Preditivo dos Testes , Fatores de Risco , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
14.
Leuk Lymphoma ; 48(5): 870-80, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17487729

RESUMO

Cyclophosphamide and doxorubicin, two important drugs in the treatment of lymphoma, exhibit a relationship between dose and fractional cell kill, and because of their toxicity profiles, they are candidates for significant dose escalation. We performed a phase II trial to determine the response rate, toxicity, and feasibility of escalated doses of both drugs as part of high dose CHOP in diffuse aggressive lymphoma. Patients who had advanced, previously untreated diffuse aggressive lymphomas (IWF E-H) and an International Prognostic Index of intermediate to high risk were eligible. Treatment was cyclophosphamide 2 gm/m(2)/day intravenously on Days 1 and 2 (total cycle dose 4 gm/m(2)), doxorubicin 35 mg/m(2)/day as a continuous infusion on Days 1 and 2 (total 70 mg/m(2)), vincristine 1.4 mg/m(2) (maximum 2 mg) on Day 1 and prednisone 100 mg/day orally on Days 1 - 5 repeated every 3 weeks for a total of four cycles. G-CSF, prophylactic antibiotics, and mesna were provided. A total of 99 patients were enrolled; 98 received therapy. Major toxicities were Grade 4 neutropenia and thrombocytopenia occurring in 97% and 92%, respectively. Serious infections occurred in 53%. Treatment-related mortality was 2%. The overall response rate is 85%, and two-year failure free and overall survival are 39% and 64%, respectively. Persistent or relapsed lymphoma was the overwhelming cause of death. Six patients have developed AML or MDS. In view of the substantial toxicity accompanying high dose CHOP, the observed outcome suggests that its efficacy is not sufficient to make further study feasible.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Recidiva , Fatores de Tempo , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
15.
Leuk Lymphoma ; 58(8): 1814-1822, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27967294

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fatores Estimuladores de Colônias/uso terapêutico , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/etiologia , Linfoma Difuso de Grandes Células B/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores Estimuladores de Colônias/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Neutropenia Febril/diagnóstico , Neutropenia Febril/epidemiologia , Feminino , Humanos , Incidência , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Rituximab , Fatores de Tempo , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
16.
J Clin Oncol ; 35(5): 552-560, 2017 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-28029309

RESUMO

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.


Assuntos
Quimioterapia de Indução/métodos , Linfoma Folicular/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Indução de Remissão , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Adulto Jovem
17.
J Clin Oncol ; 21(4): 607-14, 2003 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-12586796

RESUMO

PURPOSE: In a series of trials, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV) have been identified as effective treatments for Hodgkin's disease. We compared these regimens as initial chemotherapy for Hodgkin's disease. PATIENTS AND METHODS: Adult patients (N = 856) with advanced Hodgkin's disease were randomly assigned to treatment with ABVD or MOPP/ABV. The major end points were failure-free and overall survival, life-threatening acute toxicities, and serious long-term toxicities, including cardiomyopathy, pulmonary toxicity, myelodysplastic syndromes (MDS), and secondary malignancies. RESULTS: The rates of complete remission (76% v 80%, P =.16), failure-free survival at 5 years (63% v 66%, P =.42), and overall survival at 5 years (82% v 81%, P =.82) were similar for ABVD and MOPP/ABV, respectively. Clinically significant acute pulmonary and hematologic toxicity were more common with MOPP/ABV (P =.060 and.001, respectively). There was no difference in cardiac toxicity. There were 24 deaths attributed to initial treatment: nine with ABVD and 15 with MOPP/ABV (P =.057). There have been 18 second malignancies associated with ABVD and 28 associated with MOPP/ABV (P =.13). Thirteen patients have developed MDS or acute leukemia: 11 were initially treated with MOPP/ABV, and two were initially treated with ABVD but subsequently received MOPP-containing regimens and radiotherapy before developing leukemia (P =.011). CONCLUSION: ABVD and the MOPP/ABV hybrid are effective therapies for Hodgkin's disease. MOPP/ABV is associated with a greater incidence of acute toxicity, MDS, and leukemia. ABVD should be considered the standard regimen for treatment of advanced Hodgkin's disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Mecloretamina/uso terapêutico , Prednisona/uso terapêutico , Procarbazina/uso terapêutico , Vimblastina/uso terapêutico , Vincristina/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Intervalos de Confiança , Dacarbazina/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Feminino , Doença de Hodgkin/mortalidade , Doença de Hodgkin/patologia , Humanos , Masculino , Mecloretamina/efeitos adversos , Prednisona/efeitos adversos , Procarbazina/efeitos adversos , Taxa de Sobrevida , Vimblastina/efeitos adversos , Vincristina/efeitos adversos
18.
J Clin Oncol ; 21(1): 5-15, 2003 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-12506163

RESUMO

PURPOSE: The array of options for the initial management of follicular small cleaved lymphoma (FSCL) and follicular mixed lymphoma (FML) ranges from little or no therapy to the use of intensive combinations of drugs. The Cancer and Leukemia Group B (CALGB) compared two contrasting approaches: a single agent, and combination chemotherapy capable of curing diffuse aggressive lymphomas. PATIENTS AND METHODS: A total of 228 patients with stage III or IV FSCL or FML were randomized to cyclophosphamide or the combination of cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-B). Treatment was continued in responders for 2 years beyond maximal response. The primary end point was survival in the most common subtype, FSCL. RESULTS: Ninety-one percent of all patients responded; complete responses were seen in 66% of those treated with cyclophosphamide and in 60% treated with CHOP-B (P =.36). At 10 years with either cyclophosphamide or CHOP-B, respectively, overall time to failure (25% failure free v 33%; P =.107) and survival (44% alive v 46%; P =.79) were similar by treatment. Outcomes in FSCL also were similar. In 46 patients with FML, at 10 years the combination was associated with better failure-free (9% v 48%; P =.005) and overall (25% v 61%; P =.024) survival. Acute toxic effects were more common with combination chemotherapy. Second malignancies, which might be attributed to treatment, were seen with both approaches. CONCLUSION: There is no advantage to the initial use of the relatively intensive combination, CHOP-B, for patients with FSCL compared with the less toxic single agent, cyclophosphamide. However, in an unplanned subgroup analysis, patients with FML who received the combination experienced improved disease control and survival.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Prednisona/uso terapêutico , Vincristina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Taxa de Sobrevida
20.
Leuk Lymphoma ; 52(11): 2105-10, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21740095

RESUMO

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.


Assuntos
Linfoma não Hodgkin/psicologia , Qualidade de Vida/psicologia , Inquéritos e Questionários , Sobreviventes/psicologia , Adulto , Idoso , Fadiga/psicologia , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada
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