Ann Arbor Stage Is the Most Important Predictor of Survival for Refractory and Relapsed HIV-Associated Lymphoma Enrolled in a Program of High Dose Therapy and Autologous Peripheral Blood Stem Cell Transplantation.
Authors: Re Alessandro , Cattaneo Chiara , Michieli MariaGrazia , Casari Salvatore , Spina Michele , Rupolo Maurizio , Allione Bernardino , Ferremi Piero , Lanfranchi Arnalda , Mazzuccato Mauro , Carosi Gianpiero , Tirelli Umberto , Rossi Giuseppe 
Published: October 2019

Abstract
The recent introduction of highly active antiretroviral therapy (HAART) has allowed an aggressive treatment approach in the management of HIV-associated lymphoma (HIV-Ly). Within the Italian Cooperative Group on AIDS and Tumors (GICAT) in 2000 we started a multiinstitutional program of high dose therapy (HDT) and autologous peripheral blood stem cell transplantation (PBSCT) for HIV + patients (pts) with refractory or relapsed lymphoma. CNS lymphoma were excluded. So far, 26 pts entered the study: 10 HD (five 1st relapse, two 2nd relapse, three refractory) and 16 NHL (eight 1st relapse, one 2nd relapse, two partial remission (PR), five refractory). Median age was 38 (28–56); CD4 count 207/cmm (17–506); detectable HIV viremia: 6 pts (23%). Performance status (PS): 0–1, 7 pts (27%); 2, 19 pts (73%). Ann Arbor stage of lymphoma: II, 4 pts (15%); III, 8 pts (31%), IV, 14 pts (54%); B symptoms: 9 pts (35%); bone marrow involvement: 7 pts (27%). Median duration of last remission was 6 months (mo) (1–53). Pts received 2nd line standard dose chemotherapy as debulking treatment. Six pts were refractory and 5 died for disease progression (one is on treatment); 17 of 20 pts with chemosensitive disease successfully mobilized an adequate number of CD34+ after Cyclophosphamide + G-CSF or G-CSF-supported CT. Two pts had early disease progression, and 15 pts received the BEAM regimen and PBSCT, according to the protocol. Engraftment was prompt in all. Pts received HAART during the entire program. Neither treatment-related death nor HIV related death were registered. Fourteen pts achieved complete remission and 1 partial remission. Relapse occurred in 3 (mo +5, +8, +12); 13 are alive and 11 disease-free at 12 mo (2–28) after transplant. The median survival of the entire series (26 pts) from the study entry was 17 mo with 51% of the pts alive after a median f-up of 17 mo. From the analysis of prognostic factor, PS, Ann Arbor stage IV, B symptoms and CD4 count at study entry showed a correlation with survival by univariate, but stage IV disease was the only factor proved to correlate independently with survival on multivariate analysis. The projected overall survival for pts entering the study with stage IV disease (12 pts) or less than stage IV (14 pts) was respectively 90% vs 12% at 2 years (P < 0.001). Our data showed encouraging overall results with an intensive treatment strategy as salvage therapy for HIV-Ly. Ann Arbor stage was the most important predictor of survival. Pts with stage IV disease had poor prognosis, mainly because of chemoresistent disease, suggesting that these pts might benefit from the use of dose intensification earlier in the course of their disease.