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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Polyclonal immunoglobulin free light chain levels predict survival in myeloid neoplasms
Animesh Pardanani1, Terra L Lasho, Christy M Finke
1Mayo Clinic, Rochester, MN 55905, USA.
Insights
Elevated plasma free light chain (FLC) levels indicate a poorer survival outlook for patients with primary myelofibrosis (PMF) and myelodysplastic syndromes (MDS). This host immune response marker offers a new prognostic tool for these myeloid malignancies.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Myeloid malignancies like primary myelofibrosis (PMF) and myelodysplastic syndromes (MDS) have complex prognoses.
- Surrogate markers of host immune response are being investigated for their predictive value in cancer survival.
- Plasma immunoglobulin free light chain (FLC) concentration is a readily measurable biomarker with potential clinical applicability.
Purpose of the Study:
- To investigate whether plasma FLC concentration can serve as a prognostic biomarker for survival in patients with PMF and MDS.
- To assess the association of FLC levels with clinical parameters and conventional risk factors in these myeloid malignancies.
Main Methods:
- Two independent patient cohorts with PMF and MDS were analyzed.
- Quantitative nephelometric assay was used to measure kappa (κ) and lambda (λ) FLCs.
- Multivariable analysis was performed to evaluate FLC as an independent predictor of survival, adjusting for known risk factors.
Main Results:
- Increased FLC levels were observed in 33% of PMF patients and 46% of MDS patients.
- Elevated FLC independently predicted shortened overall survival in both PMF and MDS.
- FLC levels did not correlate with leukemia-free survival or specific genetic mutations (JAK2, MPL, IDH).
Conclusions:
- Increased plasma FLC concentration is a significant predictor of inferior survival in PMF and MDS.
- The prognostic value of FLC appears to be driven by the host immune response rather than tumor-specific factors.
- FLC measurement offers a practical and potentially broadly applicable prognostic tool for myeloid malignancies.
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.
