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Gallamini A.,Center Antoine Lacassagne | Barrington S.F.,King's College London | Biggi A.,PET Center | Chauvie S.,Medical Physics Unit | And 19 more authors.
Haematologica | Year: 2014

A retrospective, international, multicenter study was undertaken to assess: (i) the prognostic role of 'interim' positron emission tomography performed during treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point scale for the interpretation of interim positron emission tomography scan. Two hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled. Fifty-three patients with early unfavorable and 207 with advanced-stage disease were treated with doxorubicin, bleomycin, vinblastine and dacarbazine ± involved-field or consolidation radiotherapy. Positron emission tomography scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. An international panel of six expert reviewers independently reported the scans using the Deauville five-point scale, blinded to treatment outcome. Forty-five scans were scored as positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2-110) months, 252 patients are alive and eight have died. The 3-year progression-free survival rate was 83% for the whole study population, 28% for patients with interim positive scans and 95% for patients with interim negative scans (P<0.0001). The sensitivity, specificity, and negative and positive predictive values of interim positron emission tomography scans for predicting treatment outcome were 0.73, 0.94, 0.94 and 0.73, respectively. Binary concordance amongst reviewers was good (Cohen's kappa 0.69-0.84). In conclusion, the prognostic role and validity of the Deauville five-point scale for interpretation of interim positron emission tomography scans have been confirmed by the present study. © 2014 Ferrata Storti Foundation.


Song K.,Oklahoma Medical Research Foundation | Herzog B.H.,Oklahoma Medical Research Foundation | Sheng M.,Oklahoma Medical Research Foundation | Sheng M.,Jilin University | And 8 more authors.
Cancer Research | Year: 2013

Lymphomas originate in and spread primarily along the lymphatic system. However, whether lymphatic vessels contribute to the growth and spreading of lymphomas is largely unclear. Mantle cell lymphoma (MCL) represents an aggressive non-Hodgkin's lymphoma. We found that MCL exhibited abundant intratumor lymphatic vessels. Our results demonstrated that the immunomodulatory drug lenalidomide potently inhibited the growth and dissemination of MCL in a xenograft MCL mouse model, at least in part, by inhibiting functional tumor lymphangiogenesis. Significant numbers of tumor-associated macrophages expressing vascular endothelial growth factor-C were found in both human MCL and mouse MCL xenograft samples. Lenalidomide treatment resulted in a significant reduction in the number of MCL-associated macrophages. In addition, in vivo depletion of monocytes/macrophages impaired functional tumor lymphangiogenesis and inhibited MCL growth and dissemination. Taken together, our results indicate that tumor lymphangiogenesis contributes to the progression of MCL and that lenalidomide is effective in decreasing MCL growth and metastasis most likely by inhibiting recruitment of MCL-associated macrophages. © 2013 American Association for Cancer Research.


Elstrom R.L.,Center for Lymphoma and Myeloma | Andemariam B.,Center for Lymphoma and Myeloma | Andemariam B.,University of Connecticut Health Center | Martin P.,Center for Lymphoma and Myeloma | And 5 more authors.
Leukemia and Lymphoma | Year: 2012

Patients with relapsed or refractory diffuse large B-cell lymphoma may experience extended survival with second-line chemotherapy and autologous stem cell transplant (ASCT). Since a major determinant of outcome after ASCT is responsiveness to second-line therapy, the development of more effective second-line treatments is desirable. We investigated the addition of bortezomib to rituximab, dexamethasone, ifosfamide, cisplatin and etoposide (VIPER). Fifteen patients were enrolled, of whom seven were refractory to first-line chemotherapy and only three had maintained first response for 1 year. Nine (60%) patients achieved objective responses, of which three (20%) were IWC-PET (International Workshop Criteria positron emission tomography) complete responses. Median progression-free survival was 3 months, and median overall survival was 10 months. At a median follow-up of 26 months, five patients (33%) remained alive. Treatment was well tolerated with no unexpected toxicity. Although response rates did not meet predefined criteria, activity was at least comparable to other second-line approaches despite a poor-prognosis patient population. © 2012 Informa UK, Ltd.


PubMed | Center for Lymphoma and Myeloma
Type: Journal Article | Journal: Clinical lymphoma, myeloma & leukemia | Year: 2010

Patients with diffuse large B-cell lymphoma (DLBCL) who are not cured by initial therapy sometimes experience disease-free survival after autologous stem cell transplantation. Chemotherapy responsiveness before transplantation is a major predictor of outcome. Patients not responding to second-line regimens may receive third-line therapy in the hopes of achieving response, but outcome data are limited.We identified patients with relapsed or refractory DLBCL at Weill Cornell Medical Center for whom data on responses to second-line chemotherapy were available.A total of 74 patients with relapsed or refractory DLBCL who underwent second-line chemotherapy between 1996 and 2007 were identified. Of these patients, 27 (36%) did not respond. The median overall survival of nonresponding patients was 4 months, and only 1 patient (4%) survived for 1 year. The choice of third-line aggressive chemotherapy instead of less intensive approaches did not confer a survival benefit.Our data demonstrate that patients with recurrent DLBCL not responding to second-line chemotherapy demonstrate dismal outcomes. Trials of novel regimens should be prioritized as management strategies for these patients. Our data provide an important benchmark in the evaluation of the potential clinical value of such approaches.

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