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. 2019 Apr 18;133(16):1753-1761.
doi: 10.1182/blood-2019-01-893339. Epub 2019 Feb 19.

Viral, immunologic, and clinical features of primary effusion lymphoma

Kathryn Lurain  1 , Mark N Polizzotto  1 , Karen Aleman  1 , Manisha Bhutani  1 , Kathleen M Wyvill  1 , Priscila H Gonçalves  1 , Ramya Ramaswami  1 , Vickie Ann Marshall  2 , Wendell Miley  2 , Seth M Steinberg  3 , Richard F Little  1 , Wyndham Wilson  4 , Armando C Filie  5 , Stefania Pittaluga  5 , Elaine S Jaffe  5 , Denise Whitby  2 , Robert Yarchoan  1 , Thomas S Uldrick  1   6
Affiliations

Viral, immunologic, and clinical features of primary effusion lymphoma

Kathryn Lurain et al. Blood. .

Abstract

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 ∼80% of tumors are coinfected with Epstein-Barr virus (EBV). A better understanding of how KSHV-related immune dysregulation contributes to the natural history of PEL will improve outcomes. Twenty patients with PEL diagnosed between 2000 and 2013, including 19 treated with modified infusional etoposide, vincristine, and doxorubicin with cyclophosphamide and prednisone (EPOCH), were identified. We compared their clinical, virologic, and immunologic features vs 20 patients with HIV-associated diffuse large B-cell lymphoma and 19 patients with symptomatic interleukin (IL)-6 related KSHV-associated multicentric Castleman disease. Survival analyses of treated patients with PEL were then performed to identify prognostic factors and cancer-specific mortality. Compared with HIV-associated diffuse large B-cell lymphoma, PEL was associated with significant hypoalbuminemia (P < .0027), thrombocytopenia (P = .0045), and elevated IL-10 levels (P < .0001). There were no significant differences in these parameters between PEL and KSHV-associated multicentric Castleman disease. Median overall survival in treated patients with PEL was 22 months, with a plateau in survival noted after 2 years. Three-year cancer-specific survival was 47%. EBV-positive tumor status was associated with improved survival (hazard ratio, 0.27; P = .038), and elevated IL-6 level was associated with inferior survival (hazard ratio, 6.1; P = .024). Our analysis shows that IL-6 and IL-10 levels 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.

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Conflict of interest statement

Conflict-of-interest disclosure: T.S.U., M.N.P., and R.Y. are coinventors on a patent related to the treatment of KSHV-associated diseases with immune modulatory compounds; R.Y. is also coinventor on other patents not related to the current study, and his spouse is a coinventor on a number of patents, including one on the measurement of KSHV vIL-6. These inventions were all made as part of their duties as employees of the US Government, and the patents are or will be assigned to US Department of Health and Human Services. The government may convey a portion of the royalties it receives from licensure of its patents to its employee inventors. R.Y. and T.S.U. have a Cooperative Research and Development Agreement with Celgene Corp. and recently conducted clinical research using drugs supplied to the National Cancer Institute by Merck & Co., Hoffmann-La Roche, and Bayer Healthcare. R.Y. has a material Cooperative Research and Development Agreement with CTI BioPharma Corp. for the use of their drug in the laboratory. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Working case definition of KICS. CTCAE, Common Terminology for Adverse Events.
Figure 2.
Figure 2.
Clinical laboratory parameters and inflammatory cytokines in symptomatic PEL compared with KSHV-MCD and HIV-DLBCL. Between-group comparison of (A) log serum human IL-10 levels, (B) log KSHV viral loads, (C) albumin levels, and (D) platelet levels.
Figure 3.
Figure 3.
Cancer-specific survival in primary effusion lymphoma. (A) Cancer-specific survival in entire cohort, (B) according to tumor EBER status, (C) according to serum IL-6 above or below the median, and (D) according to serum IL-10 above or below the median. P values from 2-sided log-rank test. med, median.
See this image and copyright information in PMC

References

    1. Klein U, Gloghini A, Gaidano G, et al. . Gene expression profile analysis of AIDS-related primary effusion lymphoma (PEL) suggests a plasmablastic derivation and identifies PEL-specific transcripts. Blood. 2003;101(10):4115-4121. - PubMed
    1. Chang Y, Cesarman E, Pessin MS, et al. . Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma. Science. 1994;266(5192):1865-1869. - PubMed
    1. Soulier J, Grollet L, Oksenhendler E, et al. . Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman’s disease. Blood. 1995;86(4):1276-1280. - PubMed
    1. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM. Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med. 1995;332(18):1186-1191. - PubMed
    1. Ramaswami R, Chia G, Dalla Pria A, et al. . Evolution of HIV-associated lymphoma over 3 decades. J Acquir Immune Defic Syndr. 2016;72(2):177-183. - PubMed

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