Polyclonal immunoglobulin free light chain levels predict survival in myeloid neoplasms

Animesh D Pardanani, Terra L. Lasho, Christy M. Finke, S Vincent Rajkumar, Preet Paul Singh, Rhett P. Ketterling, Curtis A. Hanson, Jerry A. Katzmann, Ayalew Tefferi

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Purpose: We hypothesized that surrogate markers of host immune response may predict survival in myeloid malignancies. Because of immediate practical applicability, we chose plasma immunoglobulin free light chain (FLC) concentration as the biomarker of interest. Patients and Methods: Two independent cohorts of patients with primary myelofibrosis (PMF) or myelodysplastic syndromes (MDS) were studied. Kappa (κ) and lambda (λ) FLCs were measured by a quantitative nephelometric assay. Patients with monoclonal FLC were excluded. Results: Values that were above the upper limit of normal for κ or λ FLC were documented in 33% of 240 patients with PMF and 46% of 74 patients with MDS. Increased FLC was significantly associated with increased creatinine, and advanced age in PMF (P < .001) and hemoglobin less than 10 g/dL in MDS (P = .005). In multivariable analysis, increased FLC predicted shortened survival in both PMF and MDS, independent of age, creatinine, and other conventional risk factors. Cutoff levels based on receiver operating characteristic analysis for κ plus λ total FLCs delineated risk groups with highly significant differences in overall survival; International Prognostic Scoring System-adjusted hazard ratio in PMF was 1.9 (95% CI, 1.3 to 2.7), and was 6.3 (95% CI, 2.7 to 16.6) in MDS. No correlations were seen with leukemia-free survival, karyotype, or JAK2, MPL, or IDH mutations. In patients with PMF who were studied by cytokine profiling, the prognostic value of an increased FLC level was independent of that from circulating interleukin-2 receptor (IL-2R) or IL-8 levels. Conclusion: Increased plasma FLC concentration predicts inferior survival in both PMF and MDS. Its lack of correlation with leukemia-free survival and tumor-specific genetic markers suggests a primarily host-driven biologic phenomenon that might be more broadly applicable.

Original languageEnglish (US)
Pages (from-to)1087-1094
Number of pages8
JournalJournal of Clinical Oncology
Volume30
Issue number10
DOIs
StatePublished - Apr 1 2012

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Immunoglobulin Light Chains
Primary Myelofibrosis
Myelodysplastic Syndromes
Survival
Light
Neoplasms
Creatinine
Leukemia
Biomarkers
Biological Phenomena
Interleukin-2 Receptors
Interleukin-8
Karyotype
Genetic Markers
ROC Curve
Hemoglobins
Cytokines
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Polyclonal immunoglobulin free light chain levels predict survival in myeloid neoplasms. / Pardanani, Animesh D; Lasho, Terra L.; Finke, Christy M.; Rajkumar, S Vincent; Singh, Preet Paul; Ketterling, Rhett P.; Hanson, Curtis A.; Katzmann, Jerry A.; Tefferi, Ayalew.

In: Journal of Clinical Oncology, Vol. 30, No. 10, 01.04.2012, p. 1087-1094.

Research output: Contribution to journalArticle

Pardanani, Animesh D ; Lasho, Terra L. ; Finke, Christy M. ; Rajkumar, S Vincent ; Singh, Preet Paul ; Ketterling, Rhett P. ; Hanson, Curtis A. ; Katzmann, Jerry A. ; Tefferi, Ayalew. / Polyclonal immunoglobulin free light chain levels predict survival in myeloid neoplasms. In: Journal of Clinical Oncology. 2012 ; Vol. 30, No. 10. pp. 1087-1094.
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abstract = "Purpose: We hypothesized that surrogate markers of host immune response may predict survival in myeloid malignancies. Because of immediate practical applicability, we chose plasma immunoglobulin free light chain (FLC) concentration as the biomarker of interest. Patients and Methods: Two independent cohorts of patients with primary myelofibrosis (PMF) or myelodysplastic syndromes (MDS) were studied. Kappa (κ) and lambda (λ) FLCs were measured by a quantitative nephelometric assay. Patients with monoclonal FLC were excluded. Results: Values that were above the upper limit of normal for κ or λ FLC were documented in 33{\%} of 240 patients with PMF and 46{\%} of 74 patients with MDS. Increased FLC was significantly associated with increased creatinine, and advanced age in PMF (P < .001) and hemoglobin less than 10 g/dL in MDS (P = .005). In multivariable analysis, increased FLC predicted shortened survival in both PMF and MDS, independent of age, creatinine, and other conventional risk factors. Cutoff levels based on receiver operating characteristic analysis for κ plus λ total FLCs delineated risk groups with highly significant differences in overall survival; International Prognostic Scoring System-adjusted hazard ratio in PMF was 1.9 (95{\%} CI, 1.3 to 2.7), and was 6.3 (95{\%} CI, 2.7 to 16.6) in MDS. No correlations were seen with leukemia-free survival, karyotype, or JAK2, MPL, or IDH mutations. In patients with PMF who were studied by cytokine profiling, the prognostic value of an increased FLC level was independent of that from circulating interleukin-2 receptor (IL-2R) or IL-8 levels. Conclusion: Increased plasma FLC concentration predicts inferior survival in both PMF and MDS. Its lack of correlation with leukemia-free survival and tumor-specific genetic markers suggests a primarily host-driven biologic phenomenon that might be more broadly applicable.",
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AU - Pardanani, Animesh D

AU - Lasho, Terra L.

AU - Finke, Christy M.

AU - Rajkumar, S Vincent

AU - Singh, Preet Paul

AU - Ketterling, Rhett P.

AU - Hanson, Curtis A.

AU - Katzmann, Jerry A.

AU - Tefferi, Ayalew

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N2 - Purpose: We hypothesized that surrogate markers of host immune response may predict survival in myeloid malignancies. Because of immediate practical applicability, we chose plasma immunoglobulin free light chain (FLC) concentration as the biomarker of interest. Patients and Methods: Two independent cohorts of patients with primary myelofibrosis (PMF) or myelodysplastic syndromes (MDS) were studied. Kappa (κ) and lambda (λ) FLCs were measured by a quantitative nephelometric assay. Patients with monoclonal FLC were excluded. Results: Values that were above the upper limit of normal for κ or λ FLC were documented in 33% of 240 patients with PMF and 46% of 74 patients with MDS. Increased FLC was significantly associated with increased creatinine, and advanced age in PMF (P < .001) and hemoglobin less than 10 g/dL in MDS (P = .005). In multivariable analysis, increased FLC predicted shortened survival in both PMF and MDS, independent of age, creatinine, and other conventional risk factors. Cutoff levels based on receiver operating characteristic analysis for κ plus λ total FLCs delineated risk groups with highly significant differences in overall survival; International Prognostic Scoring System-adjusted hazard ratio in PMF was 1.9 (95% CI, 1.3 to 2.7), and was 6.3 (95% CI, 2.7 to 16.6) in MDS. No correlations were seen with leukemia-free survival, karyotype, or JAK2, MPL, or IDH mutations. In patients with PMF who were studied by cytokine profiling, the prognostic value of an increased FLC level was independent of that from circulating interleukin-2 receptor (IL-2R) or IL-8 levels. Conclusion: Increased plasma FLC concentration predicts inferior survival in both PMF and MDS. Its lack of correlation with leukemia-free survival and tumor-specific genetic markers suggests a primarily host-driven biologic phenomenon that might be more broadly applicable.

AB - Purpose: We hypothesized that surrogate markers of host immune response may predict survival in myeloid malignancies. Because of immediate practical applicability, we chose plasma immunoglobulin free light chain (FLC) concentration as the biomarker of interest. Patients and Methods: Two independent cohorts of patients with primary myelofibrosis (PMF) or myelodysplastic syndromes (MDS) were studied. Kappa (κ) and lambda (λ) FLCs were measured by a quantitative nephelometric assay. Patients with monoclonal FLC were excluded. Results: Values that were above the upper limit of normal for κ or λ FLC were documented in 33% of 240 patients with PMF and 46% of 74 patients with MDS. Increased FLC was significantly associated with increased creatinine, and advanced age in PMF (P < .001) and hemoglobin less than 10 g/dL in MDS (P = .005). In multivariable analysis, increased FLC predicted shortened survival in both PMF and MDS, independent of age, creatinine, and other conventional risk factors. Cutoff levels based on receiver operating characteristic analysis for κ plus λ total FLCs delineated risk groups with highly significant differences in overall survival; International Prognostic Scoring System-adjusted hazard ratio in PMF was 1.9 (95% CI, 1.3 to 2.7), and was 6.3 (95% CI, 2.7 to 16.6) in MDS. No correlations were seen with leukemia-free survival, karyotype, or JAK2, MPL, or IDH mutations. In patients with PMF who were studied by cytokine profiling, the prognostic value of an increased FLC level was independent of that from circulating interleukin-2 receptor (IL-2R) or IL-8 levels. Conclusion: Increased plasma FLC concentration predicts inferior survival in both PMF and MDS. Its lack of correlation with leukemia-free survival and tumor-specific genetic markers suggests a primarily host-driven biologic phenomenon that might be more broadly applicable.

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