Originally published as JCO Early Release 10.1200/JCO.2008.20.1707 on April 6 2009

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Effects of Chemotherapy in AIDS-Associated Non-Hodgkin's Lymphoma on Kaposi's Sarcoma Herpesvirus DNA in Blood

From the Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD; Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR; Division of Hematology/Oncology, University of California–San Francisco, San Francisco, CA; Beth Israel Deaconess Medical Center, Boston, MA; Divisions of Hematologic and of Solid Tumor Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY; City of Hope, Duarte, CA.

Corresponding author: Richard F. Ambinder, MD, PhD, 1650 Orleans, 389 CRB1, Baltimore, MD 21231; e-mail: ambinri{at}jhmi.edu.

Purpose To determine the relative frequency with which Kaposi's sarcoma–associated herpesvirus/HHV-8 (KSHV) DNA is detected in peripheral-blood mononuclear cells (PBMCs) and in plasma of patients with AIDS-KS and AIDS-associated non-Hodgkin's lymphoma (NHL; AIDS-NHL); to determine whether the presence of viral DNA in plasma reflects lysis of tumor cells or reflects the presence of viremia (ie, virion-encapsidated DNA); and to determine the effect of lymphoma therapy on KSHV DNA.

Patients and Methods Samples were obtained from patients enrolled in AIDS Malignancy Consortium clinical trials and from healthy donors. Real time PCR was used to quantify KSHV DNA in peripheral blood mononuclear cells (PBMC) and plasma. DNase digestion and fragment size determination studies were used to characterize the DNA detected.

Results In patients with AIDS-KS, KSHV DNA was detected in PBMC (54%) and in plasma (62%). In patients with AIDS-NHL, KSHV DNA was detected in PBMC (19%) and in plasma (22%). Median copy numbers also differed. KSHV DNA in plasma appeared to be encapsidated. In six patients with AIDS-NHL who were treated with chemotherapy (with or without rituximab), KSHV copy number declined in PBMC and in plasma.

Conclusion KSHV DNA is sometimes detected in PBMC or in plasma of patients with AIDS-NHL without KS. Among patients with KSHV DNA detected in PBMC or in plasma, copy number does not distinguish between patients with AIDS-NHL and AIDS-KS. KSHV DNA in plasma likely reflects viremia and not simply lysis of tumor or other KSHV-infected cells. KSHV DNA copy number in PBMC and in plasma declined with lymphoma-directed cytotoxic chemotherapy in each of the six patients studied.

Supported in part by Grants No. U01CA083118, U01CA070079, U01CA70058, U01CA070047, U01CA070054, U01CA070072, U01CA070080, U01CA083035, U01CA071375, U01CA083038, U01CA070062, U01CA70081, U01CA070019, U01 CA121947, and P50 CA96888 from the National Cancer Institute.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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