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Myeloma

Primary plasma cell leukemia: clinical and laboratory presentation, gene-expression profiling and clinical outcome with Total Therapy protocols

Abstract

To determine whether primary plasma cell leukemia (PPCL) remains a high-risk multiple myeloma feature in the context of contemporary therapy and gene-expression profiling (GEP), we reviewed records of 1474 patients with myeloma, who were enrolled in Total Therapy protocols or treated identically off protocol. A total of 27 patients (1.8%) were classified as having PPCL. As a group, these patients more often had low hemoglobin, high beta-2-microglobulin, high lactate dehydrogenase, low albumin and cytogenetic abnormalities. Among 866 patients with GEP results, the PPCL group more often had disease that was classified as high risk, and in CD-1 and MF molecular subgroups. Regardless of the therapeutic protocol, patients with PPCL had shorter median overall survival (OS; 1.8 years), progression-free survival (PFS; 0.8 years) and complete response duration (CRD; 1.3 years) than the remainder, whose clinical outcomes had improved markedly with successive protocols. Multivariate analyses of pretreatment parameters showed that PPCL was a highly significant independent adverse feature linked to OS, PFS and CRD. In GEP analyses, 203 gene probes distinguished PPCL from non-PPCL; the identified genes were involved in the LXR/RXR activation, inositol metabolism, hepatic fibrosis/hepatic stellate-cell activation and lipopolysaccharide/interleukin-1-mediated inhibition of RXR function pathways. Different treatment approaches building on these genomic differences may improve the grave outcome of patients with PPCL.

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Acknowledgements

This work was supported by a grant from the National Cancer Institute, National Institutes of Health, USA (Grant number CA 55813). The manuscript was edited by Peggy Brenner, Office of Grants and Scientific Publications, University of Arkansas for Medical Sciences.

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Correspondence to S Z Usmani.

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Competing interests

Dr Shaughnessy is a founder of and has an ownership stake in Signal Genetics, LLC, a biotechnology company that has licensed technology from the University of Arkansas for purposes of commercial development. He holds patents, or has submitted patent applications, on the use of GEP in cancer medicine. Dr Shaughnessy receives royalties related to patent licenses from Genzyme Novartis and Signal Genetics. He has received research funding from Celgene, Millennium and Novartis. He has advised Celgene, Genzyme, Millennium and Novartis, and has received speaking honoraria from Celgene, ArrayBioPharma, Centocor Ortho Biotech, Genzyme, Millennium and Novartis. Dr Barlogie has received research funding from Celgene and Novartis. He is a consultant to Celgene and Genzyme, and has received speaking honoraria from Celgene and Millennium. Dr Barlogie is a co-inventor on patents and patent applications related to use of GEP in cancer medicine. Dr Usmani is a consultant to Celgene, Millennium and Onyx. He has received research funding from Onyx and speaking honoraria from Celgene. All other authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Leukemia website

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Usmani, S., Nair, B., Qu, P. et al. Primary plasma cell leukemia: clinical and laboratory presentation, gene-expression profiling and clinical outcome with Total Therapy protocols. Leukemia 26, 2398–2405 (2012). https://doi.org/10.1038/leu.2012.107

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