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Open Access Research

In non-transplant patients with multiple myeloma, the pre-treatment level of clonotypic cells predicts event-free survival

Kyle J Thulien, Andrew R Belch, Tony Reiman and Linda M Pilarski*

Author Affiliations

Department of Oncology, University of Alberta and Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, T6G1Z2, Canada

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Molecular Cancer 2012, 11:78  doi:10.1186/1476-4598-11-78

Published: 19 October 2012

Abstract

Background

In multiple myeloma (MM), the immunoglobulin heavy chain VDJ gene rearrangement is a unique clonotypic signature that identifies all members of the myeloma clone independent of morphology or phenotype. Each clonotypic MM cell has only one genomic copy of the rearranged IgH VDJ.

Methods

Pre-treatment bone marrow aspirates from myeloma patients at diagnosis or in relapse were evaluated for the number of clonotypic cells using real time quantitative PCR (RPCR). RPCR measured the level of clonal cells, termed VDJ%, in 139 diagnosis and relapse BM aspirates from MM patients.

Results

Patients with a VDJ% below the median had a significantly longer event free survival (EFS) then those with a VDJ% higher than the median (p=0.0077, HR=0.57). Further, although the VDJ% from non-transplant patients predicted EFS (p=0.0093), VDJ% failed to predict outcome after autologous stem cell transplant (p=0.53).

Conclusions

Our results suggest that for non-transplant patients, the tumor burden before treatment, perhaps reflecting cancer stem cell progeny/output, is an indirect measure that may indicate the number of MM cancer stem cells and hence event free survival.

Keywords:
Multiple myeloma; Clonotypic signature; Quantitative analysis; Clinical correlates; Cancer stem cell; Autologous transplant; Tumor burden