Relationship between elevated immunoglobulin free light chain and the presence of IgH translocations in multiple myeloma

TY - JOUR

T1 - Relationship between elevated immunoglobulin free light chain and the presence of IgH translocations in multiple myeloma

AU - Kumar, S

AU - Zhang, L

AU - Dispenzieri, A

AU - Van Wier, S

AU - Katzmann, JA

AU - Snyder, M

AU - Blood, E

AU - DeGoey, R

AU - Henderson, K

AU - Kyle, RA

AU - Bradwell, Arthur

AU - Greipp, PR

AU - Rajkumar, SV

AU - Fonseca, R

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Elevated immunoglobulin free light chain (FLC) level and abnormal FLC ratio are commonly seen in multiple myeloma (MM) and have prognostic implications. We hypothesized that presence of immunoglobin heavy chain (IgH) translocations leads to unbalanced production of light chains and more extreme abnormalities of FLC, and may explain the prognostic value of FLC. We studied 314 patients with newly diagnosed MM enrolled in a phase III trial, in whom results of fluorescence in situ hybridization testing and data on serum FLC levels were available. Cytogenetic analyses and FLC estimates were performed on stored samples and results were correlated with clinical data. The median ratio (FLC ratio) and the absolute difference (FLC diff) between the involved and uninvolved FLC were higher among those with IgH translocations, especially t(14;16). In multivariate analysis, the prognostic value of FLC estimates on progression-free and overall survival were independent of high-risk IgH translocations t(4; 14) and t(14; 16). A combination of the risk factors; either abnormal FLC estimate and/or the presence of high-risk IgH translocation, achieved better prognostic stratification. We conclude that patients with IgH translocations have higher FLC levels and abnormal ratios, but the prognostic effect of FLC is only partially explained by translocation status. A system including both these risk factors allows better prediction of outcome. Leukemia (2010) 24, 1498-1505; doi:10.1038/leu.2010.128; published online 3 June 2010

AB - Elevated immunoglobulin free light chain (FLC) level and abnormal FLC ratio are commonly seen in multiple myeloma (MM) and have prognostic implications. We hypothesized that presence of immunoglobin heavy chain (IgH) translocations leads to unbalanced production of light chains and more extreme abnormalities of FLC, and may explain the prognostic value of FLC. We studied 314 patients with newly diagnosed MM enrolled in a phase III trial, in whom results of fluorescence in situ hybridization testing and data on serum FLC levels were available. Cytogenetic analyses and FLC estimates were performed on stored samples and results were correlated with clinical data. The median ratio (FLC ratio) and the absolute difference (FLC diff) between the involved and uninvolved FLC were higher among those with IgH translocations, especially t(14;16). In multivariate analysis, the prognostic value of FLC estimates on progression-free and overall survival were independent of high-risk IgH translocations t(4; 14) and t(14; 16). A combination of the risk factors; either abnormal FLC estimate and/or the presence of high-risk IgH translocation, achieved better prognostic stratification. We conclude that patients with IgH translocations have higher FLC levels and abnormal ratios, but the prognostic effect of FLC is only partially explained by translocation status. A system including both these risk factors allows better prediction of outcome. Leukemia (2010) 24, 1498-1505; doi:10.1038/leu.2010.128; published online 3 June 2010

KW - multiple myeloma

KW - translocations

KW - survival

KW - prognosis

KW - free light chain

U2 - 10.1038/leu.2010.128

DO - 10.1038/leu.2010.128

M3 - Article

C2 - 20520636

VL - 24

SP - 1498

EP - 1505

JO - Leukemia

JF - Leukemia

SN - 0887-6924

IS - 8

ER -