Purpose: Mean platelet volume (MPV) is a readily accessible and commonly tested hematological indicator. Recent studies revealed a significant impact of MPV on the course and prognosis of many diseases, including some types of cancer, as well as on the incidence of atrial fibrillation and bleeding. The study aimed to perform a retrospective analysis of MPV in terms of time to first treatment (TTFT) and to determine its prognostic value in the group of patients with chronic lymphocytic leukemia (CLL). Moreover, the study includes a retrospective analysis of platelet parameters in patients treated with ibrutinib concerning bleeding and atrial fibrillation. Patients and Methods: The study included 523 patients with CLL, for 344 the most important cytogenetic aberrations were reported. The Mann-Whitney, Kruskal-Wallis, Kaplan-Meier, chi-squared, log-rank tests and multivariate Cox proportional hazard regression model were used to analyze collected data. Results: The receiver operating characteristic curve analysis was performed to identify optimal cutoff value for MPV. The analysis of survival curves showed that in the group of patients with higher values of MPV TTFT was significantly longer than in the group with lower MPV (17.9 vs 36 months, p=0.0015, cutoff value for MPV= 10.4 fl). In multivariate Cox proportional hazard regression model low MPV, the presence of del11q and del13q provided independent prognostic value for TTFT (HR=0.69, 95%-CI, 0.5293 to 0.9081; p=0.0078; HR=1.76, 95%-CI, 1.3000 to 2.3882, p=0.0003, HR=0.74, 95%-Cl, 0.5674 to 0.9588, p=0.0229, respectively). In the group treated with ibrutinib, 59 patients had no significant correlation between MPV level and the incidence of therapy complications, although in the group of patients with low MPV there was a tendency for more frequent occurrence of atrial fibrillation (p=0.259). Conclusion: Low MPV values are associated with unfavorable prognosis and might represent a novel, independent prognostic factor in CLL.

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Basic hematological indices, such as platelets count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and plateletcrit (PCT), are readily accessible and commonly tested indicators. As platelets play a significant role in many physiological and patho- logical pathways, the abnormalities in these indices inference about irregularities within the organism, such as homeostatic disorders or inflammation. Recent studies revealed a significant impact of MPV on the course and prediction in different types of neoplasms. This review summarizes the most important studies on the impact of MPV levels on outcome and prognosis in different types of cancer conducted in recent years. MPV levels have a significant impact on the length of progression-free survival (PFS) and overall survival (OS) in many types of solid tumors, such as colorectal carcinoma, gastric cancer, pancreatic cancer, esophageal cancer, non-small cell lung cancer, breast cancer, and thyroid cancer. They also affect the prognosis in some lymphoproliferative diseases, such as diffuse large B-cell lymphoma, acute lymphoblastic leukemia, or primary and secondary myelofibrosis.

Objectives Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with heterogeneous clinical course. Recent studies revealed a link between NOTCH1 mutation and the overexpression of MYC and MYC-related genes involved in ribosome biogenesis and protein biosynthesis, such as nucleophosmin-1 (NPM1), in CLL cells. In the present study, we aim to evaluate the impact of the NOTCH1 mutation on the MYC and MYC induced NPM1 expression in CLL cells via quantification of their transcripts. Methods Using qRT-PCR, we analyzed the levels of MYC and three main NPM1 splice variants in 214 samples collected from CLL patients. We assessed the impact of each splice variant on CLL prognostic markers, including the IGHV, TP53, NOTCH1, SF3B1, and MYD88 mutational status, cytogenetic aberrations, and laboratory features. Results Significantly higher levels of NPM1.R1 transcripts in patients with unmutated compared to mutated IGHV status were found. The median time to first treatment (TTFT) in patients with a high level of NPM1.R1 was significantly shorter compared to the group with low NPM1.R1 levels (1.5 vs 33 months, p = 0.0002). Moreover, in Multivariate Cox Proportional Hazard Regression Model NPM1.R1 splice variant provided an independent prognostic value for TTFT. Conclusion In conclusion, our study indicates the prognostic significance of the level of NPM1.R1 expression and suggests the importance of splicing alterations in the pathogenesis of CLL.