Abnormal FISH in patients with immunoglobulin light chain amyloidosis is a risk factor for cardiac involvement and for death

R. Warsame, Shaji K Kumar, Morie Gertz, Martha Lacy, F. K. Buadi, S. R. Hayman, N. Leung, David M Dingli, J. A. Lust, R. P. Ketterling, Yi Lin, Stephen J Russell, L. Hwa, Prashant Kapoor, R. S. Go, S. R. Zeldenrust, R. A. Kyle, S Vincent Rajkumar, Angela Dispenzieri

Research output: Contribution to journalArticle

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Abstract

Importance of interphase fluorescent in situ hybridization (FISH) with cytoplasmic staining of immunoglobulin FISH (cIg-FISH) on bone marrow is not well understood in light chain amyloidosis (AL). This is in contrast with multiple myeloma where prognostic and treatment related decisions are dependent on cytogenetic testing. This retrospective study reviewed 401 AL patients with cIg-FISH testing performed at our institution between 2004 and 2012. Eighty-one percent of patients had an abnormal cIg-FISH. Common abnormalities involved translocations of chromosome 14q32 (52%), specifically: t(11;14) (43%), t(14;16) (3%) and t(4;14) (2%). Other common abnormalities include monosomy 13/deletion 13q (30%), trisomies 9 (20%), 15 (14%), 11 (10%) and 3 (10%). Median overall survival for this cohort of patients is 3.5 years. When plasma cell burden was greater than 10% trisomies predicted for worse survival (44 vs 19 months), and when it was ≥10% t(11;14) predicted for worse survival (53 months vs not reached). Abnormal cIg-FISH was significantly associated with advanced cardiac involvement, and remained a prognostic factor on multivariate analysis. This large AL cohort demonstrates that abnormal FISH at diagnosis is prognostic for survival and advanced cardiac disease. Particularly, trisomies and t(11;14) affect survival when degree of plasma cell burden is considered.

Original languageEnglish (US)
Article numbere310
JournalBlood Cancer Journal
Volume5
Issue number5
DOIs
StatePublished - May 1 2015

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Immunoglobulin Light Chains
Amyloidosis
Fluorescence In Situ Hybridization
Immunoglobulins
Survival
Staining and Labeling
Trisomy
Plasma Cells
Monosomy
Interphase
Multiple Myeloma
Cytogenetics
Heart Diseases
Multivariate Analysis
Retrospective Studies
Chromosomes
Bone Marrow
Light

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Abnormal FISH in patients with immunoglobulin light chain amyloidosis is a risk factor for cardiac involvement and for death. / Warsame, R.; Kumar, Shaji K; Gertz, Morie; Lacy, Martha; Buadi, F. K.; Hayman, S. R.; Leung, N.; Dingli, David M; Lust, J. A.; Ketterling, R. P.; Lin, Yi; Russell, Stephen J; Hwa, L.; Kapoor, Prashant; Go, R. S.; Zeldenrust, S. R.; Kyle, R. A.; Rajkumar, S Vincent; Dispenzieri, Angela.

In: Blood Cancer Journal, Vol. 5, No. 5, e310, 01.05.2015.

Research output: Contribution to journalArticle

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abstract = "Importance of interphase fluorescent in situ hybridization (FISH) with cytoplasmic staining of immunoglobulin FISH (cIg-FISH) on bone marrow is not well understood in light chain amyloidosis (AL). This is in contrast with multiple myeloma where prognostic and treatment related decisions are dependent on cytogenetic testing. This retrospective study reviewed 401 AL patients with cIg-FISH testing performed at our institution between 2004 and 2012. Eighty-one percent of patients had an abnormal cIg-FISH. Common abnormalities involved translocations of chromosome 14q32 (52{\%}), specifically: t(11;14) (43{\%}), t(14;16) (3{\%}) and t(4;14) (2{\%}). Other common abnormalities include monosomy 13/deletion 13q (30{\%}), trisomies 9 (20{\%}), 15 (14{\%}), 11 (10{\%}) and 3 (10{\%}). Median overall survival for this cohort of patients is 3.5 years. When plasma cell burden was greater than 10{\%} trisomies predicted for worse survival (44 vs 19 months), and when it was ≥10{\%} t(11;14) predicted for worse survival (53 months vs not reached). Abnormal cIg-FISH was significantly associated with advanced cardiac involvement, and remained a prognostic factor on multivariate analysis. This large AL cohort demonstrates that abnormal FISH at diagnosis is prognostic for survival and advanced cardiac disease. Particularly, trisomies and t(11;14) affect survival when degree of plasma cell burden is considered.",
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AU - Kumar, Shaji K

AU - Gertz, Morie

AU - Lacy, Martha

AU - Buadi, F. K.

AU - Hayman, S. R.

AU - Leung, N.

AU - Dingli, David M

AU - Lust, J. A.

AU - Ketterling, R. P.

AU - Lin, Yi

AU - Russell, Stephen J

AU - Hwa, L.

AU - Kapoor, Prashant

AU - Go, R. S.

AU - Zeldenrust, S. R.

AU - Kyle, R. A.

AU - Rajkumar, S Vincent

AU - Dispenzieri, Angela

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N2 - Importance of interphase fluorescent in situ hybridization (FISH) with cytoplasmic staining of immunoglobulin FISH (cIg-FISH) on bone marrow is not well understood in light chain amyloidosis (AL). This is in contrast with multiple myeloma where prognostic and treatment related decisions are dependent on cytogenetic testing. This retrospective study reviewed 401 AL patients with cIg-FISH testing performed at our institution between 2004 and 2012. Eighty-one percent of patients had an abnormal cIg-FISH. Common abnormalities involved translocations of chromosome 14q32 (52%), specifically: t(11;14) (43%), t(14;16) (3%) and t(4;14) (2%). Other common abnormalities include monosomy 13/deletion 13q (30%), trisomies 9 (20%), 15 (14%), 11 (10%) and 3 (10%). Median overall survival for this cohort of patients is 3.5 years. When plasma cell burden was greater than 10% trisomies predicted for worse survival (44 vs 19 months), and when it was ≥10% t(11;14) predicted for worse survival (53 months vs not reached). Abnormal cIg-FISH was significantly associated with advanced cardiac involvement, and remained a prognostic factor on multivariate analysis. This large AL cohort demonstrates that abnormal FISH at diagnosis is prognostic for survival and advanced cardiac disease. Particularly, trisomies and t(11;14) affect survival when degree of plasma cell burden is considered.

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