LAUSR

Multiple myeloma (MM) is the second most frequent hematological neoplasia, characterized by the accumulation of malignant plasma cells within the marrow microenvironment leading to variable anemia, bone pain, renal impairment, hypercalcemia and infections. Virtually all cases of MM arise from monoclonal gammopathy of uncertain significance (MGUS), associated to a deep re-shape of the microenvironment and T-cell function. In MGUS, T-cells isolated from the bone marrow are able of mounting vigorous response against autologous pre-malignant cells while this phenomenon is not observed in MM. Indeed, in MM the immune function is impaired as consequence of an immunologically hostile microenvironment and cellular defects. MM plasma cells are able of immune editing through reduction of immune-surveillance, and expansion of myeloid derived suppressor cells as recently described in MM patients both at diagnosis and during chemotherapy . Several groups, including ours, identified NLR (the ratio between absolute neutrophils counts, ANC and absolute lymphocyte count, ALC) and LMR (the ratio between absolute lymphocyte counts, ALC and absolute monocyte count, AMC), as predictor of progression free survival (PFS) and overall survival (OS) in patients with hematological cancers , including MM, as surrogate of a defective immune system. Several studies have searched for prognostic biomarkers before treatment start to choice the type and intensity of initial treatment. Recently, it has been proposed that the International Staging System should be associated to FISH results but the latter are not always available at diagnosis to address a tailored therapy. We have shown that the combination of ISS with NLR is able to predict outcome in patients treated upfront with novel agents. Indeed, NLR-ISS could identify patients that could benefit of single-novel agent based treatment and our results also confirm those recently published in another series that included patients treated with either novel agents (VMP, MPT) or older schemes (MP, VAD). It has published that NLR> 2 can be considered a bad prognostic factor for both PFS and OS in MM, as previously noticed in myeloma and lymphoma. We read with interest the analysis recently reported by Dosani et al. highlighting a LMR ratio< 3.6 as predictor of PFS and OS, also in patients with adverse cytogenetics, to stratify patients based on their baseline immune status. Thus, we reviewed files of 208 consecutively newlydiagnosed MM patients followed at our institution between January 2006 and June 2013, enrolled in observational or phase 3 clinical trials active in our Institutions (GIMEMA MMY-3006, RV-MM-PI209) for patients eligible to high-doses chemotherapy. Details on treatment regimens and final or ongoing results of these studies have previously been reported. All studies were approved by our Institutional Review Board. Patients provided written informed consent before entering the studies, which were performed in accordance with the Declaration of Helsinki. In all patients, complete blood count (CBC) and routine biochemical examinations were taken on every visit. White blood cell count and types (neutrophil, lymphocyte, eosinophil, and monocyte) were determined by electrical impedance method in automatic blood counter device (Beckman Coulter LH 750). NLR and LMR were calculated using data obtained from the CBC count. Baseline characteristics of evaluated patients are listed in