BCL-2 Expression May Adversely Affect Outcome in HIV-Associated Systemic Diffuse Large B Cell Lymphoma.
Authors: Ezzat Hatoon , Filipenko J. Doug , Vickars Linda M. , Galbraith Paul F. , Li Charles H. , Murphy Kevin , Montaner Julio , Harris Marianne , Hogg Robert , Vercauteren Suzanne , Leger Chantal S. , Zypchen Leslie , Leitch Heather A. 
Published: October 2019

Abstract
BCL-2 expression in diffuse large B cell lymphoma (DLBCL) in HIV-negative patients (pts) is associated with inferior outcome, an effect at least partially overcome by the addition of rituximab (R) to multi-agent chemotherapy (MA-CT). The effect of BCL-2 expression on DLBCL outcome in HIV-positive pts is less well defined. We performed a retrospective clinical-pathological correlation in 141 pts with systemic HIV-associated lymphoma seen at St. Paul’s Hospital between 1982 and 2004; this analysis includes 36 DLBCL since 1992. Clinical DLBCL data were obtained by chart review; HIV-associated data from the data-base of the BC Centre For Excellence in HIV/AIDS. Stored biopsy material diagnostic of DLBCL was sectioned and stained for BCL-2 expression. Median age at DLBCL diagnosis (dx) was 42 (range 20–64)y, DLBCL stage advanced 27; ECOG PS >1 n=11; median LDH ratio 1.4 (0.5–8.6); IPI >2 n=11; CD4 at DLBCL dx >100 n=21; prior AIDS dx n=18; hepatitis B and/or C n=9; on highly active anti-retroviral therapy (HAART) at DLBCL dx n=11; BCL-2+ n=11. HAART with DLBCL treatment (tx) n=17; received CHOP-R n=9, CHOP or ACOP n=18; G-CSF n=10; herpes virus tx n=10; PCP prophylaxis n=35. Significant factors for inferior overall survival (OS) included prior AIDS, median OS (MS) 3.2 vs. 7.4 mo with no AIDS; no HAART use, MS 2.6 vs. 5.2 mo with HAART; BCL-2+, MS 3.2 vs. 5.2 mo for BCL-2 negative; and receiving MA-CT without R, MS 3.8 vs. 7.6 mo for MA-CT + R (p<0.05 for all factors). Though a statistically significant effect could not be confirmed, the use of MA-CT + R appeared to improve progression-free survival (PFS) in BCL-2+ DLBCL, PFS 3 of 3 pts at 2.3 mo (2 on HAART) vs. 2 of 6 (33%, 2 on HAART) PFS at 2.1 mo for MA-CT without R. PFS for 6 pts receiving HAART and MA-CT + R (3 BCL-2+) was 100% at 2.3 mo, while for 12 pts receiving HAART and MA-CT without R (2 BCL-2+), median PFS was 2.0 (range 1–10.1) mo or 55% PFS at 2.1 mo. For pts not receiving HAART; MA-CT (n=4, 2 BCL-2+), 3 progressed at 0.5, 5.3 and 8.8 mo and died of DLBCL, and one died of treatment-related toxicity at 2.6 mo; MA-CT + R, 2 of 2 pts (neither BCL-2+) progressed at 3 and 11 mo. There were 15 documented episodes of treatment-related toxicity in 13 of 24 pts (54%) in the MA-CT group and 24 episodes in 7 of 9 pts (79%) in the MA-CT + R group (p<0.76). There were 13 (54%) toxic deaths with MA-CT vs. 2 (22%) with MA-CT + R (neither pt receiving HAART; p<0.07) as opposed to 2 (22%) and 13 (54%), respectively, deaths from DLBCL (p<0.02). Overall mortality was MA-CT n=19 (79%); MA-CT + R n=4 (44%), p<0.07. In conclusion, in this single-centre series of 36 pts with HIV-associated systemic DLBCL, of pts receiving no HAART, outcome was inferior in BCL-2+ DLBCL, an effect not seen with HAART. BCL-2+ DLBCL had inferior outcome in pts receiving MA-CT, an effect not seen with MA-CT + R. These data suggest that in BCL-2+ DLBCL in HIV, HAART and rituximab with chemotherapy are important in overcoming a BCL-2 effect.