HIV-Associated Plasmablastic Lymphoma: A Multi-Institutional Study

Plasmablastic lymphoma (PBL) is a distinct subtype of B-cell lymphoma strongly associated with HIV infection with no more than 150 cases reported in the literature. We conducted a retrospective study to evaluate clinicopathological characteristics and determine prognostic factors in HIV-associated PBL (HIV PBL).

Institutions in the United States (US) and internationally submitted clinical and pathological patient-level data on HIV-positive individuals who had a pathological diagnosis of PBL. According to WHO criteria, all the cases were required to have a plasmablastic morphology, be CD20-negative and to express at least one plasmacytic marker (i.e. CD38, CD138 and/or MUM1/IRF4). Continuous and categorical variables are presented using descriptive statistics. Univariate survival analyses were performed using the Kaplan-Meier method and the log-rank test. Cox proportional-hazard regression test was used for the multivariate survival analysis. P-values of less than 0.05 were considered statistically significant.

Thus far, data on 45 patients have been obtained from 11 institutions. Twenty cases (44%) were from Europe, 17 (38%) from the US, 4 (9%) from Africa and 4 (9%) from South America. The median age was 43 years (range: 19–66 years). Of 45 patients studied, 78% (n=35) were men. The median CD4⁺ count was 177 cells/mm³ (range: 17–683 cells/mm³). The median duration of HIV infection prior to PBL diagnosis was 6 years (range 0–26 years), and 80% (n=36) received HAART. PBL was the initial presentation of HIV infection in 29% (n=13) of the patients. The median viral load at presentation was 45,000 copies/ml (range: undetectable to 4.7 million copies/ml). At presentation, 69% (n=25) of patients exhibited B symptoms, 44% (n=20) had extranodal involvement, 65% (n=28) presented with stage III or IV disease, 20% (n=9) had oral involvement and 39% (n=12) had an absolute lymphocyte count (ALC) <1000 cells/mm³. EBV-encoded RNA was expressed in 94% (n=31), Ki67 >90% was seen in 66% (n=21) and MYC rearrangement was detected in 50% (n=10) of tested patients. Chemotherapy was employed in 89% (n=39) of patients, with 59% (n=23) receiving CHOP. A minority (n=4; 10%) underwent HSCT. Complete response (CR) was obtained in 69% (n=22); however, after 48 months of follow-up, 66% of patients (n=29) have died. The median overall survival (OS) was 11 months (95% CI 7–20 months) from diagnosis. The most common cause of death was PBL progression (n=18; 62%). At the univariate level, adverse prognostic factors for survival included non-CR to chemotherapy (p =0.002), ALC <1000 cells/mm³ (p =0.006), MYC rearrangement (p =0.0005), ECOG performance status >1 (p =0.048), female sex (p =0.02), and advanced stage (p =0.047). At the multivariate level, ALC <1000 cells/mm³ and non-CR were independent adverse prognostic factors in patients with HIV PBL (p =0.01 and p =0.02, respectively).

PBL is a rare aggressive B-cell lymphoma, which tends to affect young HIV-positive men who have CD4⁺ counts <200 cells/mm³. Advanced stage, extranodal involvement, and tumors with EBER expression, MYC rearrangements and Ki67 >90% at presentation are common features of HIV PBL. Although showing a 69% CR to chemotherapy, the median OS remains poor at 11 months. In the multivariate survival analysis, ALC <1000 cells/mm³ and lack of achievement of CR to chemotherapy were independent adverse prognostic factors in HIV PBL. In the HAART era, HIV PBL seems to have a shorter median OS than other HIV-associated aggressive B-cell lymphomas.

Montoto:Genentech: Research Funding; Roche: Honoraria. Vose:GSK: Research Funding; Millenium: Research Funding; Celgene: Research Funding; BMS: Research Funding; Exelixis: Research Funding; SBio: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding. Castillo:GlaxoSmithKline: Research Funding; MIllennium Pharmaceuticals: Research Funding.