Morphological and Immunohistochemical Prognostic Factors of Multiple Myeloma and their Correlation with Clinical and Laboratory Indicators of Morbidity. Summary of the Doctoral Thesis

Abstract

Multiple myeloma accounts for 13% of hematologic malignancies. MM affects not only older people, but also persons of working age (35% of all) and 2% of patients are younger than 40 years.The importance of MM research is denoted by the growing incidence of the disease in the Western world and in Latvia in recent years. MM incidence has increased from 4.06 in year 2008 to 5.5 in year 2017 per 100’000 inhabitants.Over the last 20 years early diagnostics and novel treatment options have allowed for an increase in MM patient life expectancy up to 10–20 years after diagnosis, and the five-year survival rate has reached 50%.The MM workup includes serological, radiological, cytological, and histological tests that allow to verify the diagnosis, estimate the prognosis and treatment efficacy. Immunohistochemical detection of a variety of biomarker combinations in bone marrow biopsies has an important prognostic role of MM. The aim of the study was to find correlations between morphological, immunohistochemical features of the bone marrow with clinical and laboratory prognostic parameters and clinical stages of MM.Bone marrow trephine biopsies of 122 MM patients were analysed: amount of plasma cells, percentages of myeloma cells with plasmablastic morphology, myeloma cell infiltration type, bone marrow cellularity, degree of myelofibrosis, aberrant and myeloma cells expression of oncogenic immunohistochemical markers – CD56, BCL2, p53, cyclin D1, p21.The results were expressed as mean (M) ± standard deviation (SD) or percentage and range. Normality was assessed using the D’Agostino-Pearson omnibus normality test. Correlation between histological, clinical and laboratory parametric data were determined by Spearman's tests. It was found that increased bone marrow cellularity, microosteolytic lesion, high myeloma cell numbers, increased percentage of the myeloma cells with plasmablastic morphology, diffuse and mixed myeloma cell infiltration patterns were associated with worse clinical and laboratory prognostic parameters such as elevated serum ß2 microglobulin and creatinine levels, higher M-protein, decreased albumin and haemoglobin levels, renal insufficiency, and advanced stages of Salmon Durie classification.We have proved that CD56 negative and p53 positive MM patients’ groups correlate with the higher levels of ß2 microglobulin, renal insufficiency, low platelet count, decreased haemoglobin levels and advanced stages of Salmon-Durie classification.A statistically significant correlation was found between cyclin D1 expression in myeloma cells and the following prognostically poor clinical and laboratory findings – increased ß2 microglobulin serum levels, hypercalcaemia, clinically and radiologically proven bone damage or fractures, advanced stages of Salmon-Durie classification.There was proved that a statistically significant correlation exists between p21 antigen expression in myeloma cells and the following laboratory and clinical features: higher M-protein, decreased albumin level and advanced stages of Salmon-Durie classification.We recommend to investigate bone marrow material with such a combination of histological changes: amount of plasma cells percentages of myeloma cells with plasmablastic morphology, myeloma cell infiltration type, bone marrow cellularity, aberrant and myeloma cells expression of oncogenic immunohistochemical markers – CD56, BCL2, p53, cyclin D1, p21for the prediction of MM course.