title: 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.
authors.affiliation: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. susmani@uams.edu
authors.forename: S Z
authors.initials: SZ
authors.lastname: Usmani
authors.forename: B
authors.initials: B
authors.lastname: Nair
authors.forename: P
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authors.lastname: Qu
authors.forename: E
authors.initials: E
authors.lastname: Hansen
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authors.lastname: Zhang
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authors.lastname: Petty
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authors.lastname: Waheed
authors.forename: J D
authors.initials: JD
authors.lastname: Shaughnessy
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authors.lastname: Alsayed
authors.forename: C J
authors.initials: CJ
authors.lastname: Heuck
authors.forename: F
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authors.lastname: van Rhee
authors.forename: T
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authors.lastname: Milner
authors.forename: A
authors.initials: A
authors.lastname: Hoering
authors.forename: J
authors.initials: J
authors.lastname: Szymonifka
authors.forename: R
authors.initials: R
authors.lastname: Sexton
authors.forename: J
authors.initials: J
authors.lastname: Sawyer
authors.forename: Z
authors.initials: Z
authors.lastname: Singh
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authors.lastname: Crowley
authors.forename: B
authors.initials: B
authors.lastname: Barlogie
mesh_terms: D000368:Aged; D002985:Clinical Protocols; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007952:Leukemia, Plasma Cell / Q000235:genetics* / Q000628:therapy*; D008297:Male; D016896:Treatment Outcome