Screening for Residual Disease in Pediatric Burkitt Lymphoma Using Consensus Primer Pools

Assessing molecular persistent or minimal residual disease (PD/MRD) in childhood Burkitt lymphoma (BL) is challenging because access to original tumor is usually needed to design patient-specific primers (PSPs). Because BL is characterized by rearranged immunoglobulin heavy chain (IgVH) genes, IgVH primer pools from IgVH1–IgVH7 regions were tested to detect PD/MRD, thus eliminating the need for original tumor. The focus of the current study was to assess the feasibility of using IgVH primer pools to detect disease in clinical specimens. Fourteen children diagnosed with B-NHL had follow-up repository specimens available to assess PD/MRD. Of the 14 patients, 12 were PD/MRD negative after 2 months of therapy and remained in remission at the end of therapy; 2/14 patients were PD/MRD positive at 2-3 months and later relapsed. PSP-based assays from these 14 patients showed 100% concordance with the current assay. This feasibility study warrants further investigation to assess PD/MRD using IgVH primer pools, which could have clinical significance as a real-time assessment tool to monitor pediatric BL and possibly other B-cell non-Hodgkin lymphoma therapy

HIV DNA and Dementia in Treatment-Naive HIV-1-Infected Individuals in Bangkok, Thailand

High HIV-1 DNA (HIV DNA) levels in peripheral blood mononuclear cells (PBMC) correlate with HIV-1-associated dementia (HAD) in patients on highly active antiretroviral therapy (HAART). If this relationship also exists among HAART-naïve patients, then HIV DNA may be implicated in the pathogenesis of HAD. In this study, we evaluated the relationship between HIV DNA and cognition in subjects naïve to HAART in a neuro AIDS cohort in Bangkok, Thailand. Subjects with and without HAD were recruited and matched for age, gender, education, and CD4 cell count. PBMC and cellular subsets were analyzed for HIV DNA using real-time PCR. The median log10 HIV DNA copies per 106 PBMC for subjects with HAD (n=15) was 4.27, which was higher than that found in subjects without dementia (ND; n=15), 2.28, p\u3c 0.001. This finding was unchanged in a multivariate model adjusting for plasma HIV-1 RNA levels. From a small subset of individuals, in which adequate number of cells were available, more HIV DNA was in monocytes/macrophages from those with HAD compared to those with ND. These results are consistent with a previous report among HAART-experienced subjects, thus further implicating HIV DNA in the pathogenesis of HAD

HIV DNA and Dementia in Treatment-Naïve HIV-1-Infected Individuals in Bangkok, Thailand

High HIV-1 DNA (HIV DNA) levels in peripheral blood mononuclear cells (PBMC) correlate with HIV-1-associated dementia (HAD) in patients on highly active antiretroviral therapy (HAART). If this relationship also exists among HAART-naïve patients, then HIV DNA may be implicated in the pathogenesis of HAD. In this study, we evaluated the relationship between HIV DNA and cognition in subjects naïve to HAART in a neuro AIDS cohort in Bangkok, Thailand. Subjects with and without HAD were recruited and matched for age, gender, education, and CD4 cell count. PBMC and cellular subsets were analyzed for HIV DNA using real-time PCR. The median log(10) HIV DNA copies per 10(6) PBMC for subjects with HAD (n=15) was 4.27, which was higher than that found in subjects without dementia (ND; n=15), 2.28, p<0.001. This finding was unchanged in a multivariate model adjusting for plasma HIV-1 RNA levels. From a small subset of individuals, in which adequate number of cells were available, more HIV DNA was in monocytes/macrophages from those with HAD compared to those with ND. These results are consistent with a previous report among HAART-experienced subjects, thus further implicating HIV DNA in the pathogenesis of HAD

A phase 1b/pharmacokinetic trial of PTC299, a novel post-transcriptional VEGF inhibitor, for AIDS-related Kaposi’s sarcoma: AIDS Malignancy Consortium trial 059

Vascular endothelial growth factor (VEGF) plays an important role in Kaposi’s sarcoma (KS). We administered PTC299, a post-transcriptional inhibitor of pathogenic VEGF, to persons with HIV-related KS. Seventeen participants received three different doses of PTC299. Adverse events typically observed with VEGF-inhibition were absent. Three participants had partial tumor responses and 11 had stable disease. There were no differences in exposure to PTC299 by antiretroviral regimen. Serum VEGF, but not KSHV DNA, decreased on treatment. Given redundancies in the VEGF feedback loop, future trials should consider combining PTC299 with agents that inhibit different pathways implicated in KS and KSHV proliferation

Viruses and cancer.

N01 PC035137/PC/NCI NIH HHS/United State