High Dose Therapy and Autologous Peripheral Blood Stem Cell Transplantation as Salvage Therapy for HIV-Associated Lymphoma: Result of the GICAT Study.
Authors: Re Alessandro , Michieli Mariagrazia , Cattaneo Chiara , Rupolo Maurizio , Casari Salvatore , Spina Michele , Allione Bernardino , Almici Camillo , Ferremi Piero , Abruzzese Luciano , Simonelli Cecilia , Manuele Rosa , Levis Alessandro , Carosi Giampiero , Tirelli Umberto , Rossi Giuseppe 
Published: April 2020

The introduction of highly active antiretroviral therapy (HAART) has allowed the use of intensive treatments for HIV+ patients (pts) with malignancies. In 2000 we started a multiinstitutional prospective study of high dose therapy (HDT) and autologous peripheral blood stem cell transplantation (PBSCT) as salvage treatment for HAART responding HIV+ pts with primary refractory or relapsed Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Aim of the study was to test both the feasibility and efficacy in unselected pts. Pts showing chemoresistance or progressive disease (PD) during debulking treatment or failing PBSC collection were excluded and analysed according to the intention to treat. From May 2000 to Feb 2007 50 pts entered the study. 31 had NHL and 19 HL (20 refractory disease, 5 partial remission (PR), 22 first and 3 second relapse); median age was 39 (28–59); 60% stage IV disease; CD4 count was 218/mcl (17–561) and 11 pts had CD4 &lt; 100; 22% had detectable HIV-viremia. Pts first received debulking chemotherapy (CT) at discretion of centers (2–4 courses): 2 died from toxicity and 10 had PD; 1 pt retracted and 6 failed PBSC mobilization. In 31 pts CD34+cells were collected (median 5.9x10e6/kg), after Cyclophosphamide 4g/mq + G-CSF (12 pts) or at recovery after CT (19 pts). Four pts had early PD and 27 received HDT (BEAM) according to the protocol (median time to N and PLT engraftment was 10 and 12 days). 10 pts underwent consolidation radiotherapy. Pts received HAART during the entire program (in 7 a brief discontinuance was necessary). Treatment toxicity was mainly gastrointestinal (8 grade III mucositis/enteritis and 1 grade IV mucositis) and hepatic (2 grade III). There were 9 FUO and 2 sepsis (S.epidermidis and E.coli), 1 Clostridium colitis, 1 Ps. aeruginosa pneumonia and 2 reactivation of perianal abscess. Infections in the first 2 years included 6 HZ, 2 esophagus candidosis, 1 CMV corioretinitis and 4 CMV reactivation with no disease. The CD4 count decreased after PBSCT (median 190.5/mcl pre PBSCT and 119.5 at +3), with recovery after few ms (157 at +6 and 285.5 at +12). 3 pts had PD after PBSCT (2 after a brief PR) and 3 relapsed after complete remission (CR) at +5, +8 and +12. 21 of 27 pts are alive and disease free (17 CR and 4 CRu), after a f-up of 44 mo (2–70), (OS 74% and PFS 75%). The median survival of the entire series (50 pts) from the enrolment was 33 ms with an OS of 49% and a PFS of 50% (follow-up 45 ms). Ann Arbor stage IV and CD4 &lt;100/mcl were associated with a worse prognosis (stage IV vs Stage &lt; IV: OS 35% vs 72%;P=.003; CD4 &lt; 100 vs &gt; 100: OS 18% vs 59%;P=.001). Pts enrolled with PR or relapse had an OS of 62% compared with 32% of pts primary refractory (P=0.09). This study confirms on a large series the feasibility of HDT and PBSCT in HIV+ pts and shows its high long-term efficacy as salvage treatment in HIV-associated lymphoma. Less than 50% of pts couldn’t benefit this procedure, mainly because of advanced disease or severe immunodeficiency; earlier use of HDT in the course of their disease could be advisable.