Autologous Stem Cell Transplantation Is Effective in Chemosensitive HIV-Associated Lymphoma Irrespective of Previous Therapy and Histological Subtype
Authors: Re Alessandro , Bianchetti Nicola , Cattaneo Chiara , Casari Salvatore , Pagani Chiara , Peli Annalisa , Focà Emanuele , ferremi Leali Pierino , Almici Camillo , Castelli Francesco , Rossi Giuseppe 
Published: October 2019

Abstract
Introduction: Autologous stem cell transplantation (ASCT) is considered safe and effective in patients with HIV-associated lymphoma (HIV-Ly). The reported studies usually analyze togheter different histological subtypes, including classical Hodgkin lymphoma (HL) and a variety of aggressive non Hodgkin lymphoma (NHL), and different indications for ASCT, and report composite outcomes.
Aim: We report our single center experience on a large single institution series of patients (pts) with HIV-Ly undergoing ASCT and analyse efficacy according to histology subtypes, indications for ASCT, previous therapy and lymphoma status at transplant, to understand the settings where this treatment approach is most effective and useful.
Methods: Retrospective analysis of clinical characteristics and outcome of all consecutive pts with HIV-Ly transplanted at our Institution from March 2001 to February 2018.
Results: 62 pts with HIV-Ly underwent ASCT during the study period. Ninety-four % were male; median age was 46 years (range, 29-62). Lymphoma histology was HL in 11 (18%), diffuse large B-cell lymphoma in 22 (35%), Burkitt or Burkitt-like in 13 (21%) , plasmablastic in 10 (16%), T-cell aggressive NHL (3 anaplastic large cell lymphoma, ALK negative, and 1 extranodal NK/T-cell lymphoma, nasal type) in 4 (6%), and indolent B-cell lymphoma (1 follicular lymphoma, and 1 extranodal marginal zone lymphoma) in 2 (3%) pts, respectively. Median CD4+ cells count at ASCT was 208/mL (range, 55-720); 8 pts (13%) had detectable HIV viral load. Eighteen pts (29%) had concomitant hepatitis C and 2 (3%) hepatitis B infection. Indications for ASCT were primary refractory disease (26%), first or subsequent relapse (37%), and consolidation after first line therapy for partial remission (PR) or high risk complete remission (CR) (37%). At the time of ASCT, 10 pts (16%) were in first CR, 45 (73%) had chemosensitive disease (i.e. first PR, chemosensitive relapse/refractory disease), and 7 (11%) had disease refractory to the last chemotherapy (CT) received. Twenty-three patients (37%) had received only 1 line of CT before ASCT, 29 (47%) 2 lines, and 10 (16%) 3 or more lines. Conditioning regimen was BEAM in 47 patients (76%), FEAM in 13 (21%), and 1 each Mitoxantrone-Melphalan and BiCNU-Thiotepa. All pts were receiving cART throughout ASCT except 3 who suspended cART for at least 1 week, due to toxicity and/or oral mucositis. Neutrophil engraftment (neutrophils > 500/mcl) occurred in all pts at a median of 10 days (range, 8-12), and platelet engraftment (platelet count > 20.000/mcl) occurred in all pts at a median of 13 days (range, 9-46), except in one with refractory disease who died of sepsis early after ASCT (treatment-related mortality 1.6%). Twenty-three pts (70%) experienced grade 3-4 toxicity, including oral mucositis (17 patients), gastrointestinal toxicity (8), hepatic toxicity (1), and seizures (1). Twenty-five pts (41%) had an episode of fever of unknown origin. Before engraftment, 22 documented bacterial infections, 1 fungal infection, 2 herpes zoster infections and 5 CMV reactivations were recorded. After a median follow-up of 59 months (range, 1-177) from ASCT, the 5 years-progression free survival (5y-PFS) and OS (5y-OS) were 66.6% and 69.7% respectively, with no significant differences according to different histologies (figure 1). The outcome was satisfactory regardless of the indication for transplant (primary refractory disease, 5y-PFS 50% and 5y-OS 49% , relapse, 5y-PFS 62.6% and 5y-OS 70.7%, and first line consolidation, 5y-PFS 80.3% and 5y-OS 80.1%, P=NS), and number of CT lines before ASCT (1 line, 5y-PFS 80.3% and 5y-OS 80.1%, 2 lines, 5y-PFS 61.3% and 5y- 63.4%, and 3 or more lines, 5y-PFS 53.3% and 5y-OS 66.7%, P=NS). According to the status of lymphoma at the time of ASCT, pts in first CR had a 5y-PFS of 77.8% and 5y-OS of 77.8% and pts with chemosensitive disease 73.7% and 80.3%, while all chemorefractory pts died within 5 months from ASCT, with median PFS and OS of 2 and 3 months respectively (P< 0.001) (figure 2).
Conclusion: This is the largest single institution series of HIV-Ly receiving ASCT. We confirm the feasibility and long-term efficacy of this treatment approach in different histological subtypes. ASCT was beneficial also in primary refractory disease and heavily pre-treated pts, provided that lymphoma proved chemosensitive to the last CT received before ASCT.

Disclosures
Rossi: ABBVIE: Other: ADVISORY BOARD; PFIZER: Other: ADVISORY BOARD; SANDOZ: Honoraria; GILEAD: Other: ADVISORY BOARD; AMGEN: Other: ADVISORY BOARD; SANOFI: Other: ADVISORY BOARD; JANNSEN: Other; JAZZ: Other: ADVISORY BOARD; TEVA: Other: ADVISORY BOARD; CELGENE: Other: ADVISORY BOARD; ROCHE: Other: Advisory Board; NOVARTIS: Honoraria; MUNDIPHARMA: Honoraria; BMS: Honoraria.