الفهرس 
MULTIPLE MYELOMAOnly 14 pages are availabe for public view
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Abstract
MM is a neoplastic PC disorder that is characterized by clonal proliferation of malignant PCs in the BM microenvironment, M protein in the blood or urine, and associated organ dysfunction. It accounts for approximately 1% of all cancers and 10% of hematologic malignancies. The disease is slightly more common in men and in African Americans.
The diagnosis of MM requires 10% or more clonal PCs on BM examination or a biopsy proven plasmacytoma and evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions i.e. CRAB) that is felt to be related to the underlying PC disorder. Treatment, although not curative, is intended to control the disease and minimize its end-organ effects.
The natural history of MM is heterogeneous with survival times ranging from a few weeks to >20 years. Analysis of prognostic factors is essential to compare outcomes within and between clinical trials. Prognosis in MM depends on host factors (age, performance status, and comorbidities), disease stage and aggressiveness together with response to therapy. Staging of MM using the Durie–Salmon staging or the ISS provides prognostic information but is not helpful in making therapeutic choices.
In the context of cytogenetics and prognosis in MM, deletions of 13q14 were shown to be an unfavorable prognostic variable when detected by interphase FISH. It was reported that the loss of 13q14 is not solely an independent prognostic factor, however, its prognostic value is attributed to its association with other cytogenetic abnormalities.
Recent advances in flow cytometry have permitted more specific and sensitive evaluations of PC populations. One of the advantages of multiparameteric flowcytometry is the generation and identification of markers that allow the unequivocal identification of PCs among other hematopoietic cells, and the identification of aberrant PC phenotypes that help to discriminate between normal and neoplastic PCs. Moreover, several marker combinations, particularly that of CD117 and CD28, in addition to CD19, show promise in predicting outcome for MM.
In light of that, the aim of this study was to evaluate the prognostic significance of del13q14 together with CD19, CD28 and CD117 expression in PCs as regards their impact on OS as well as clinical outcome of the newly diagnosed MM patients.
The material of this work included 25 newly diagnosed cases of MM whose ages ranged from 40 to 83 years old, with male : female ratio of 1.5:1, who were subjected to full history taking, clinical examination, routine workup of MM including CBC with peripheral blood film examination, biochemical profile including; serum total protein, albumin, calcium, creatinine, LDH and β2M in addition to detection of BJP in urine. Also SPEP as well as IF were performed for the detection of M protein and its type in addition to light chain type. Radiological investigations including x-ray, CT scan and/or MRI were also done for detection of lytic bone lesions. BM samples were analysed for morphological examination as well as evaluation of the expression of CD19, CD28 and CD117 by flow cytometry and detection of del13q14 by FISH.
Individual analysis of CD19, CD28 and CD117 expression in relation to disease characteristics of MM patients showed no significant association. On the other hand, CD19+ as well as CD28+ expressions showed poor prognostic impact on MM patients’ OS but had no impact on their clinical outcome. However, CD117 expression had no prognostic impact on neither OS nor clinical outcome of the studied MM patients.
The simultaneous study of CD28/117 expression revealed four patterns of expression; double positive (CD28+/117+), double negative (CD28-/117-), CD28+/117- and CD28-/117+. These patterns had no significant association with MM patients’ disease characteristics. However, CD28-/117- expression seems to have a good prognostic impact as regards OS. In addition, CD28+/117- pattern of expression showed poor prognostic impact regarding both OS and clinical outcome. However, the other patterns of expression; CD28-/117+ and CD28+/117+, had no impact on neither MM patients’ OS nor their clinical outcome.
Del13q14 had a significant association with serum M protein level. However, it did not show any significant association with the other disease characteristics of the studied MM cases. Moreover, it showed a non significant impact on neither their OS nor clinical outcome.
Other factors including demographic and laboratory data of the MM patients were also studied for their prognostic impact regarding OS and clinical outcome. It was shown that only the increasing age of the studied MM patients had a highly significant poor prognostic impact on their OS but not on their clinical outcome. The remaining data showed no significant prognostic impact on neither their OS nor clinical outcome.
In conclusion, these findings suggest that antigenic expression of PCs, particularly the CD28+/CD117-immunophenotype as well as positive expression of CD19 and CD28, may contribute to identify MM patients with high risk of progression and shorter survival. Whereas the study of del13q14 by FISH has no sole value in the prediction of MM patients’ survival or clinical outcome.