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The Revised International Staging System (R-ISS) stratifies patients affected by Multiple Myeloma (MM) into three distinct risk groups: R-ISS I [ISS Stage I, Standard-Risk cytogenetics and normal Lactase DeHydrogenase (LDH)], R-ISS III (ISS stage III and either high-risk cytogenetics or high LDH) and R-ISS II (any other characteristics). With the aim to verify whether the three R-ISS groups could be divided into subgroups with different prognostic factors based on the detection of Circulating Plasma Cells (CPCs) at diagnosis, in this retrospective analysis, we evaluated 161 patients with MM treated at our centre between 2005 and 2017. In all, 57 patients (33·9%) were staged as R-ISS III, 98 (58·3%) as R-ISS II and six (3·6%) as R-ISS I. CPCs were detected in 125 patients (74·4%), while in 43 patients (25·6%) no CPCs were seen. Our analysis revealed that Overall Survival (OS) and progression-free survival (PFS) rates in R-ISS II patients were higher in the subgroup without CPCs compared to the subgroup with ≥1 CPCs (OS: 44·7% vs. 16·3%, P = 0·0089; PFS: 27·8% vs. 8·1%, P = 0·0118). Our present findings suggest that the detection of CPCs at diagnosis may be used as a further prognostic biomarker to improve the risk stratification of patients with MM staged as R-ISS II.

Introduction Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia (AML) with a life-threatening coagulopathy. Once it is suspected, ATRA should be started. Appreciation of APL details is critical, but an experienced hematopathologist may not be available. We developed an algorithm, based on the parameters generated by automated blood cell counter ADVIA 2120i Siemens that can aid the diagnosis of APL. Methods All parameters in the algorithm were selected on the bases of the pathophysiology of the APL and the analyzer's technology. We used c1 cutoff: PLT 2; %saturated cells ≥ 1; % blasts > 4. Satisfying at least five of six cutoffs, we obtained an "APL criteria". It was tested on 247.209 raw-data from routine and emergency samples and on 124 raw-data from APL. We performed a multiparametric analyses and obtained definitive cutoffs (c2). It was validated on a new group of 51.002 raw-data from routine and emergency. Finally, it was tested on AML and ALL, MDS, MPN, oncologic samples, and hemolytic and megaloblastic anemia. Results The algorithm provided a high sensitivity (86.30%) and high specificity (99.83%) in APL with high or normal number of WBC and satisfactory results in APL with cytopenia (80%). The specificity was very high also in groups of hematological and nonhematological diseases. It can be used as an "APL criteria" to alert pathologists of the possible presence of APL. It together with instrumental and classical morphology may allow to reduce the time of diagnosis with further reduction in early death.

Detection of circulating plasma cells (PCs) in multiple myeloma (MM) patients is a well-known prognostic factor. We evaluated circulating PCs by flow cytometry (FC) in 104 patients with active MM at diagnosis by gating on CD38(+) CD45(-) cells and examined their relationship with cytogenetic risk. Patients had an average follow-up of 36 months. By using a receiver operating characteristics analysis, we estimated the optimal cut-off of circulating PCs for defining poor prognosis to be 41. Patients with high-risk cytogenetics (n = 24) had poor prognosis, independently of circulating PC levels [PC 41 vs. PC ≥ 41: overall survival (OS) = 0% vs. OS = 17%, P = not significant (n.s.); progression-free survival (PFS) = 0% vs. 17%, P = n.s.]. Patients with standard-risk cytogenetics (n = 65) showed a better prognosis when associated with a lower number of circulating PCs (PC 41 vs. PC ≥ 41: OS = 62% vs. 24%, P = 0·008; PFS = 48% vs. 21%, P = 0·001). Multivariate analysis on the subgroup with standard-risk cytogenetics confirmed that the co-presence of circulating PCs ≥ 41, older age, Durie-Salmon stageI and lack of maintenance adversely affected PFS, while OS was adversely affected only by lactate dehydrogenase, older age and lack of maintenance. Our results indicate that the quantification of circulating PCs by a simple two-colour FC analysis can provide useful prognostic information in newly diagnosed MM patients with standard-risk cytogenetics.

Deletions of the long arm of chromosome 6 are known to occur at relatively low frequency (3-6%) in chronic lymphocytic leukemia (CLL), and they are more frequently observed in 6q21. Few data have been reported regarding other bands on 6q involved by cytogenetic alterations in CLL. The cytogenetic study was performed in nuclei and metaphases obtained after stimulation with a combination of CpG-oligonucleotide DSP30 and interleukin-2. Four bacterial artificial chromosome (BAC) clones mapping regions in bands 6q16, 6q23, 6q25, 6q27 were used as probes for fluorescence in situ hybridization in 107 CLL cases in order to analyze the occurrence and localization of 6q aberrations. We identified 11 cases (10.2%) with 6q deletion of 107 patients studied with CLL. The trends of survival curves and the treatment-free intervals (TFI) of patients with deletion suggest a better outcome than the other cytogenetic risk groups. We observed two subgroups with 6q deletion as the sole anomaly: two cases with 6q16 deletion, and three cases with 6q25.2-27 deletion. There were differences of age, stage, and TFI between both subgroups. By using BAC probes, we observed that 6q deletion has a higher frequency in CLL and is linked with a good prognosis. In addition, it was observed that the deletion in 6q16 appears to be the most frequent and, if present as the only abnormality, it could be associated with a most widespread disease.

Multiple Myeloma (MM) is a clonal B-cell disorder characterized by accumulation of malignant plasma cells (PCs) in the bone marrow (BM). Circulating PCs can be detected in the peripheral blood of a significant proportion of patients with MM and their presence is a well-known prognostic factor. Indeed, the appearance of circulating PCs in the blood could indicate relative indipendence from adhesion to the microenvironment, thus implying more aggressive disease. In this study, we examined the relationship between the number of PCs and citogenetic risk in patients with newly diagnosed MM. We analyzed peripheral blood from patients with Monoclonal Gammopathy of Undetermined Significance (MGUS; n=15), Smoldering Myeloma (SM; n=28), Solitary Plasmacytomas (SP; n=3) and active Multiple Myeloma (MM; n=105). These patients were followed by the U.O.C. Ematologia at the "Mazzoni" Hospital from January 2006 to December 2013, with a median follow-up of 25 months. We analyzed clinical, laboratory and cytogenetic data of patients with active MM. However, cytogenetic analysis was not evaluable for 15 patients. The number of circulating PCs was detected by flow cytometry using a simple two-colours approach. Cells were stained with fluorescence-labeled CD38 and CD45 antibodies and 50,000 events were acquired and analyzed for each patient. PCs were identified by gating on CD38bright+/CD45- cells. Using a receiver operating characteristics (ROC) analysis, we assessed that ³41circulating PCs is the optimal cut-off for defining poor prognosis. The 8-years probability of Overall Survival (OS) and Progression-Free Survival (PFS) in patients with I and lack of maintenance therapy, adversely affected OS and PFS. All patients with SP showed no circulating PCs. In all cases of MGUS or SM, circulating PCs, when detected, were In summary, our results suggest that the quantification of circulating PCs by flow cytometry could provide useful prognostic information in newly diagnosed MM patients with standard-risk cytogenetics. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.