# Clonal Immunoglobulin DNA and Lymphoma Diagnosis

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $141,985

## Abstract

Project Summary
 Aggressive lymphomas associated with HIV infection are often curable with chemotherapy.
Chemotherapy failures are much more common in patients with poor performance status, which manifests as
advanced stage disease and is typically associated with a delayed diagnosis. The diagnosis of lymphoma in HIV
patients is particularly challenging, and often delayed, because the signs and symptoms of lymphadenopathy,
fever, night sweats, and weight loss characteristic of lymphoma may also reflect HIV, or opportunistic infections
such as tuberculosis (TB). In South Africa, the diagnosis of lymphoma is especially difficult because of the high
incidence of TB co-infection, which is the major cause of death in HIV patients. Fine needle aspiration (FNA) is
often performed on palpable and enlarged lymph nodes as a front-line diagnostic procedure. The FNA is
sometimes suggestive of lymphoma or TB, and is sometimes indeterminate or non-diagnostic.
Lymphadenopathy in this setting is so common, and the medical infrastructure to support excisional biopsy and
pathology stretched so thin, that definitive excisional biopsies must be prioritized. Those with FNA findings
suspicious for lymphoma are sent for excisional biopsy, while others are treated empirically for TB, and only
proceed to biopsy if lymphadenopathy is persistent or progressive despite TB treatment. We propose an
investigation of molecular markers that may serve as diagnostic adjuncts to improve prioritization for excisional
biopsy. The approach involves molecular analysis of immunoglobulin DNA to detect clonal rearrangements in
FNA or in plasma specimens. Several studies suggest that circulating tumor DNA can be detected in the plasma
of >95% of patients with aggressive B cell lymphomas. We suspect that these rearrangements would also be
frequently detected in FNA as well.
 We propose to study FNA and plasma specimens from 300 HIV patients with lymphadenopathy
undergoing FNA for standard clinical indications at the University of the Witwatersrand-affiliated hospitals and
clinics in Johannesburg, South Africa. From this group of patients we will identify at least 30 patients with
definitive lymphoma (diagnosed by excisional biopsy) and 30 without lymphoma. To make these clinical
determinations (lymphoma vs. no-lymphoma), we will follow patients for up to 6 months while standard diagnostic
and therapeutic procedures are pursued. When 30 true positive, and corresponding true negative, cases have
been identified, we will determine whether clonal immunoglobulin (cIg) DNA is present in FNA, plasma, or both
in order to estimate the sensitivity, specificity, positive predictive value and negative predictive value of cIg DNA
as a diagnostic adjunct. These studies will also give insight into clonal B-cell proliferations associated with HIV
and coinfections. Positive findings from this preliminary study will set the groundwork for a real-time prospective
study to determine whether more rapid diagnosi...

## Key facts

- **NIH application ID:** 10127596
- **Project number:** 5R21CA232891-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RICHARD Frederick AMBINDER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $141,985
- **Award type:** 5
- **Project period:** 2020-03-13 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127596

## Citation

> US National Institutes of Health, RePORTER application 10127596, Clonal Immunoglobulin DNA and Lymphoma Diagnosis (5R21CA232891-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10127596. Licensed CC0.

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