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

Melissa Agsalda,David Troelstrup,Bruce Shiramizu,Ian Kusao

doi:10.1155/2009/412163

Melissa Agsalda, David Troelstrup + Show 2 more

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https://doi.org/10.1155/2009/412163

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Abstract

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.

Highlights

The prognosis for children diagnosed with Burkitt lymphoma (BL) has improved dramatically over the last decade; a significant percentage (30–40%) of children with advanced disease remain unresponsive to or relapse during therapy, those with B-cell non-Hodgkin lymphoma (NHL) [1,2,3]
The current study was designed to assess persistent disease or minimal residual disease (PD/MRD) on followup specimens from pediatric B-NHL cases regardless of whether primary diagnostic tissue was available from the time of diagnosis
We hypothesized that PD/MRD could be screened in specimens using primer pools made up of immunoglobulin heavy chain variable region (IgVH) oligomers from respective VH1 to VH7 families

Summary

Introduction

The prognosis for children diagnosed with Burkitt lymphoma (BL) has improved dramatically over the last decade; a significant percentage (30–40%) of children with advanced disease remain unresponsive to or relapse during therapy, those with B-cell non-Hodgkin lymphoma (NHL) [1,2,3]. Because the prognosis for children who relapse during therapy is dismal, with an estimated 2-year overall survival of 10–30%, improvements in early detection of disease may improve their overall disease-free survival [2]. In such cases, identifying persistent disease or minimal residual disease (PD/MRD) could be important if the paradigm of early intervention when PD/MRD is found can be translated from other pediatric cancers such as acute lymphoblastic leukemia [4]. The current study hypothesizes that detection of PD/MRD in BL cases may be accomplished by more efficient means and not require primary diagnostic tissue to design unique PSP.

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