الفهرس 
Multiple MyelomaOnly 14 pages are availabe for public view
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Abstract
Multiple myeloma is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated B cells with the accumulation of malignant plasma cells in the bone marrow compartment. It accounts for approximately 1% of all malignant diseases, 10% of all hematological malignancies in whites and 20% in African Americans.
Clinically, patients are characterized by excess bone marrow plasma cells, serum and /or urine monoclonal protein, osteolytic bony lesions, anemia, hypercalcemia and renal impairment. This disease is considered heterogenous both at the genetic level and in terms of clinical outcome.
Chromosomal aberrations in MM are typically complex and represent a hallmark of the disease, involving many chromosomes that are altered both numerically and structurally.
Among all prognostic factors described in MM, FISH abnormalities have been found to be the most predictive of outcomes. In addition to their prognostic value, there is some evidence that cytogenetic abnormalities may confer unique clinical and immunological disease characteristics, which may underlie their prognostic significance. Furthermore, poor outcomes associated with HR cytogenetic groups, have led to efforts to identify treatments and combinations with the potential to improve prognosis of patients with these abnormalities.
The low proliferative activity of the tumor cells early in the disease is an important limitation of conventional cytogenetics (karyotyping) since only dividing cells can be analyzed. Yet, this limitation has been overcome by the use of molecular cytogenetic techniques as FISH, CGH, Gene expression profiling (GEP) and single nucleotide polymorphism (SNP) arrays. Nowadays, the standard diagnostic work up for myeloma includes both I-FISH and traditional metaphase chromosomal studies as a surveillance to monitor the therapeutic response and at relapse to help direct therapy.
The present study was done on 60 newly diagnosed Egyptian myeloma patients and aimed to detect chromosomal aberrations by I-FISH and their relation to patients’ outcomes and prognoses.
All the patients were subjected to complete history, clinical and laboratory examination. Moreover, we have also tested the expression of numerical aberrations involving chromosome 5 ,9 and 15 , del 17 p ,14 q deletion , t(11,14), t(4,14), del 13q14 and t(14;16) by FISH probes on bone marrow samples collected from the patients at diagnosis (before starting therapy) and after adding interleukin 6 to the culture media to enhance its growth.
Staging and risk stratification of patients were carried out to detect the outcome of the disease.
In our study, hyperdiploidy is the most common cytogenetic aberration and has a significant relation with response to treatment (was associated with good prognosis where 90% of responders have hyperdiploidy) & with staging using (RISS) (where100% of patients lie within stages I and II) these results were supported by both Kaplan -Meier analysis and Multivariate and univariate logistic analysis
Kaplan –Meier analysis shows that there was statistically significant relation found between hyperdiploidy results and event free survival among the studied patients where overall survival was higher among hyperdiploidy patients.
Multivariate logistic regression analysis shows that the most important predictors of the response to treatment was found to be kappa light chain restriction and staging by both ISS and RISS together with hyperdiploidy, whereas univariate analysis revealed significant association between response to treatment and (kappa light restriction & staging by ISS) with, followed by staging by RISS and finally hyperdiploidy.
Followed by 17 p del in the second place, those patients were significantly presented with hypercalcemia and lambda restriction.
In our study, a highly significant statistical relation was found between staging by (RISS) and both t (4;14) and 14 q rearrangements with. In addition a significant statistical relation was found between del 13q and IPT.