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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.

SUBMITTER: Usmani SZ

PROVIDER: S-EPMC3426639 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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

Usmani S Z SZ Nair B B Qu P P Hansen E E Zhang Q Q Petty N N Waheed S S Shaughnessy J D JD Alsayed Y Y Heuck C J CJ van Rhee F F Milner T T Hoering A A Szymonifka J J Sexton R R Sawyer J J Singh Z Z Crowley J J Barlogie B B

Leukemia 20120417 11

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 an ...[more]

PMID: 22508408

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Project description:Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren's syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, cholinergic agents, and scrupulous oral and dental care. Complications of cirrhosis from advanced PBC include esophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatoma formation.

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

Publications

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

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