Viral, immunologic, and clinical features of primary effusion lymphoma

Kathryn Lurain, Mark N. Polizzotto, Karen Aleman, Manisha Bhutani, Kathleen M. Wyvill, Priscila H. Gonçalves, Ramya Ramaswami, Vickie Ann Marshall, Wendell Miley, Seth M. Steinberg, Richard F. Little, Wyndham Wilson, Armando C. Filie, Stefania Pittaluga, Elaine S. Jaffe, Denise Whitby, Robert Yarchoan and Thomas S. Uldrick

Key points

  • Primary effusion lymphoma in people with HIV is associated with a Kaposi sarcoma herpesvirus-driven IL-6 and IL-10-related syndrome.

  • EBV status of the tumor and elevated serum IL-6 are prognostic in primary effusion lymphoma.


Primary effusion lymphoma (PEL) is an aggressive HIV-associated lymphoma with a relatively poor prognosis in the era of effective HIV therapy. Kaposi sarcoma herpesvirus (KSHV) is the etiologic agent, and approximately 80% of tumors are Epstein Barr virus (EBV) co-infected. A better understanding of how KSHV-related immune dysregulation contributes to the natural history of PEL will improve outcomes. We identified 20 PEL patients diagnosed 2000-2013, including 19 treated with modified infusional etoposide, vincristine, and doxorubicin with cyclophosphamide and prednisone (EPOCH) and compared their clinical, virologic, and immunologic features with 20 patients with HIV-associated diffuse large B-cell lymphoma (HIV-DLBCL) and 19 patients with symptomatic interleukin (IL)-6 related KSHV-associated multicentric Castleman disease (KSHV-MCD). We then performed survival analyses of treated PEL patients to identify prognostic factors and cancer-specific mortality. Compared to HIV-DLBCL, PEL was associated with significant hypoalbuminemia (p<0.0027), thrombocytopenia (p=0.0045), and elevated IL-10 (p<0.0001). There were no significant differences in these parameters between PEL and KSHV-MCD. Median overall survival in treated PEL patients was 22 months with a plateau in survival noted after two years. Three-year cancer-specific survival was 47%. EBV+ tumor status was associated with improved survival (hazard ratio 0.27; p=0.038), and elevated IL-6 was associated with inferior survival (hazard ratio 6.1, p=0.024). Our analysis shows IL-6 and IL-10 contribute to the natural history of PEL. Inflammatory cytokines and tumor EBV status are the strongest prognostic factors. Pathogenesis directed first-line regimens are needed to improve overall survival in PEL.

  • Submitted January 3, 2019.
  • Accepted February 8, 2019.