Absolute lymphocyte count as a prognostic marker in newly diagnosed multiple myeloma patients

Sir, Multiple myeloma (MM), a malignant disorder of plasma cells, is the second most common hematologic malignancy. Different prognostic strategies are used to stratify patients at the time of the diagnosis. The survival of MM patients has improved significantly in the last decade. This improvement can be attributed especially to the use of novel agents in the therapy of MM patients [1]. These include especially two classes of drugs: the immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide) and proteosome inhibitors (bortezomib, carfilzomib). Several studies suggest a prognostic significance for the absolute lymphocyte count (ALC), as a surrogate marker of the immune status [2], at diagnosis and after autologous stem cell transplantation (ASCT) [3] in patients with myeloma and that the quantitative numbers of CD19 cells at MM diagnosis are associated with superior survival [4]. Myeloma cells survival is dependent on microenvironmental interactions in their niche. Recently, the role of tumor-associated macrophages (TAM) was studied also in the pathogenesis of multiple myeloma. It was shown that macrophages support myeloma cell growth, viability, and drug resistance [5]. Increased peripheral blood absolute monocyte count (AMC) has been reported to be a poor prognostic factor in malignant lymphoproliferative disorders and also in solid tumors [6, 7]. The relationship between the number of circulating monocytes and clinical outcomes was mainly attributed to their role as precursors of TAM. A prognostic significance was also reported for the LMR (lymphocyte/monocyte ratio) in newly diagnosed myeloma patients [8] and also at the start of the conditioning regimen of autologous stem cell transplantation (ASCT) [9]. Until now, to our best knowledge, the statistical value of these measures has not been verified in patients treated with novel agents. We retrospectively evaluated these simple measurable markers, the AMC, the ALC, and the LMR at diagnosis of multiple myeloma patients in our hospital and evaluated their prognostic value in patients treated with novel agents. This study included new multiple myeloma patients who were diagnosed between 2006 and 2014 at Galilee Medical Center, Nahariya, Israel. The diagnosis was made according to the IMWG guidelines for symptomatic MM. Approval for review of the records was obtained from the Institutional Review Board of the Galilee Medical Center. AMC and ALC were obtained at diagnosis from routine complete blood count calculated by Advia 2120 hematology analyzer (Simens). We also collected demographic and clinical characteristics of the patients from their records. Quantity data were described by median and range. Qualitative data were described by frequencies and percentages. Comparisons of quantity data between groups were examined by independent sample t-test or Wilcoxon ranks sum test, as appropriate. Correlation of qualitative variables was examined by chi-squared test or Fisher’s exact test, as appropriate. Overall survival (OS) was measured from the time of diagnosis to the date of death or last follow-up. Univariate and multivariate survival analysis was performed using Cox Regression Model and Kaplan–Meier method with Log Rank (Mantel-Cox) test. All P-values represented were one-sided, and a pvalue<0.05 was considered statistically significant. Sixty-two newly diagnosed MM patients were evaluated. The median age was 69 years (range: 46–88 years); 35 (56.5%) patients were male and 27 (43.5%) female. The paraprotein type was as follows: 33 (55%) IgG, 14 (23.3%) light chain and 13 (21.7%) IgA; 15 (25%) patients were ISS I, 16 (26.7%) were ISS II, 29 (48.3%) were ISS III. Forty (64.5%) patients were treated with chemotherapy, 16 (25.8%) were treated with chemotherapy followed by ASCT, and 6 (9.7%) patients had conservative therapy. Fifty-one patients (82%) were treated with novel agents at diagnosis. The median follow-up for the whole cohort after the diagnosis was 28.2 mo (range 0.5–98.8 months). At the time of writing, 41 (66.1%) of patients were living. The optimal cutoff for the ALC and AMC, and the LMR was set at 1600/lL,