S K Barta1, M S Samuel2, X Xue3, D Wang3, J Y Lee4, N Mounier5, J-M Ribera6, M Spina7, U Tirelli7, R Weiss8, L Galicier9, F Boue10, R F Little11, K Dunleavy12, W H Wilson12, C Wyen13, S C Remick14, L D Kaplan15, L Ratner16, A Noy17, J A Sparano2. 1. Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia. Electronic address: stefan.barta@fccc.edu. 2. Department of Medical Oncology, Montefiore Medical Center, Bronx. 3. Department of Epidemiology and Population Health, Albert Einstein Cancer Center, Bronx. 4. Department of Biostatistics, University of Arkansas, Little Rock, USA. 5. Groupe d'Etude des Lymphomes de l'Adulte (GELA), France. 6. ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute and PETHEMA Group, Badalona, Spain. 7. Department of Medical Oncology, National Cancer Institute, Aviano, Italy. 8. Private Practice for Hematology and Oncology, Bremen, Germany. 9. Department of Immunology, Hopital St Louis, Assistance Publique-Hopitaux de Paris, Paris. 10. Department of Internal Medicine and Immunology, Hopital Antoine Beclere, Clamart, France. 11. Clinical Investigations Branch. 12. Department of Medical Oncology, National Cancer Institute, Bethesda, USA. 13. Department of Internal Medicine, University Hospital Cologne, Cologne, Germany. 14. Mary Babb Randolph Cancer Center, West Virginia University, Morgantown. 15. Department of Hematology and Oncology, University of California San Francisco, San Francisco. 16. Division of Oncology, Washington University School of Medicine, St Louis. 17. Memorial Sloan-Kettering Cancer Center and Weill Cornell, Lymphoma Service, New York, USA.
Abstract
BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.
BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positivepatients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positivepatients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.
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