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Contribution of new immunoglobulin-derived biomarkers in plasma cell dyscrasias and lymphoproliferative disorders

World Journal of Hematology 2013年第2期2卷 6-12页

作者： marie-christine kyrtsonis Dimitrios Maltezas Efstathios Koulieris Tatiana Tzenou Stephen J Harding Haematology Section of 1~(st) Department of Propaedeutic Internal Medicine Athens Medical SchoolLaikon University Hospital 11527 Athens Greece The Binding Site Group Ltd. BirminghamB151QT United Kingdom

New assays for serum immunoglobulin(Ig) free and heavy chain quantification were developed for routine clinical practice. Serum free light chain(s FLC) assay was shown to improve detection, management and prognostication in all plasma cell dyscrasias. More precisely, s FLC measurements proved to be prognostic for the progression of monoclonal gammopathy of undetermined significance and smoldering multiple myeloma(MM), became markers of response and survival in amyloid light-chain amyloidosis and contributed to accurate follow-up of patients with light chain and non secretory MM. In addition, s FLC and they ratio(s FLCR) were shown useful for the prognosis and monitoring of intact Ig myeloma; their evaluation was incorporated in the new uniform response criteria. s FLC or s FLCR were also observed abnormal in B-cell non-Hodgkin lymphoma/chronic lymphocytic leukemia(CLL). Moreover, increased s FLC levels, summated s FLC or abnormal s FLCR predict shorter overall survival in early-stage CLL while increased s FLC constituted an independent, adverseprognostic factor for event-free and overall survival in diffuse large B-cell lymphoma and Waldenstrom's macroglobulinemia. Clinical applications of heavy Ig chain separately(HLC) measurements are more recent and mainly concern MM in which HLC deriving ratios correlated with parameters of disease activity and constituted an adverse survival marker.

关键词： Immunoglobulin quantification FreeliteTM HevyliteTM Diagnosis Monitoring Prognosis

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Biology and Treatment of Skeletal Manifestations in Multiple Myeloma

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Journal of Cancer Therapy 2014年第4期5卷 387-402页

作者： Nikolaos A. Stavropoulos Argyro Papadoyiannis Dimitris Maltezas Petros Stavrou George C. Babis Panayiotis J. Papagelopoulos Gerasimos A. Pangalis marie-christine kyrtsonis 1st Department of Orthopaedics Attikon University General Hospital University of Athens Medical School Haidari Athens Greece 2nd Department of Orthopaedics Konstantopouleio General Hospital N. Ionia University of Athens Medical School N. Ionia Athens Greece Hematology Clinic Athens Medical Center Psychiko Branch Psychiko Athens Greece Hematology Section of First Department of Propedeutic Internal Medicine National and Kapodistrian University of Medicine Laikon University Hospital Athens Greece Section of Internal Medicine General Hospital of Lakonia Sparti Greece Spine Clinic American Medical Center Nicosia Cyprus

MM is frequently associated with the development of osteolytic bone lesions, osteoporosis and pathological fractures. Bone destruction in MM is caused by osteoclasts recruited in areas adjacent to myeloma plasma cells;their contact triggers both cell types to secrete soluble factors sustaining one each other’s activation and proliferation. Osteoclasts differentiate and maturate upon binding of the receptor activator of NF-kappaB ligand (RANKL), secreted by bone marrow microenvironmental cells, to its receptor (RANK) on osteoclast progenitors, while osteoprotegerin (OPG), a natural decoy receptor, can block the aforementioned ligation. At the same time osteoblasts are inactivated by the Wnt/β-catenin signaling pathway inhibitor, Dickkopf-1 protein (DKK-1), secreted by malignant plasma cells. Furthermore, DKK-1 deregulates the OPG/RANKL equilibrium, promoting osteoclastogenesis. Myeloma bone disease (MBD) can be treated with myeloma-directed chemotherapy and agents inhibiting bone resorption such as aminobisphosphonates, although new promising biology driven monoclonal antibodies targeting osteoclastogenesis mechanisms are emerging. Palliative MBD treatment includes analgesics, orthotics, radiation therapy, vertebroplasty and kyphoplasty. In case of spinal cord compression, radiation therapy or surgical decompression, should be instantly performed, along with steroid administration. Surgery may also be an option especially in case of weight-bearing bone fractures. MBD is a morbid complication and should be carefully managed because it deteriorates patients’ quality of life and worsens disease outcome.

关键词： Multiple Myeloma Skeletal Manifestations Biology Treatment

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