Prognostic Significance of the FISH Panel for Patients with Multiple Myeloma

Abstract 5001

Multiple Myeloma (MM) is a malignancy of terminally differentiated B lymphocytes which is characterized by the accumulation of clonal Plasma Cells (PC) in the Bone Marrow (BM). The pathological BM cells from patients with MM are characterized by genetic instability that results in numerical and structural chromosomal abnormalities, which may serve prognostic factors.

Conventional Cytogenetics (CC) in MM is difficult and often fails to provide reliable information due to the low proliferative index of neoplastic PC, and also because of the usually low numbers of PC in the samples of the BM aspirations. CC hampers the systematic evaluation when the pathological clone does not proliferate but, interphaseFluorescence in situ Hybridization (FISH) analysis is an attractive alternative for evaluation of chromosomal changes.

This study analyzed the frequency and clinical significance of chromosomal aberrations among BM samples from 53 patients with MM. They were investigated by CC and FISH as part of a routine clinical evaluation of the patients. CC was informative (abnormal karyotypes) in eight (15%) patients. Although somelaboratories perform FISH in combination with PC detection, we performed a FISH test on the same samples used for the CC analysis.

We designed a single test as routine based on interphaseFISH with a panel of probes for the detection of 4 chromosomal aberrations, most frequently found, in patients with MM. The test involved probes for the detection of 1q21, 13q14, 14q32, as first screening for the subsequent translocations t(4;14)(p16;q32), t(11;14) (q13;q32), t(14;16) (q32;q23) and t(14;20)(q32;q11), and 17p13. We compared the prognostic information in the presence or absence of abnormal metaphases (ploidy) with the FISH Panel outlined above.

Eight patients presented abnormal cytogenetics: hypodiploid (1), hyperdiploid (3) and complex (4) karyotypes respectively. Among these patients, 6 were positive according to the FISH Panel. Deletion of 17p13 was observed in the patients with the hypodiploid karyotype, as well as in two patients with complex karyotypes; deletion of 13q14 and rearrangement of 14q23 were observed in the patients with complex karyotypes and gain of 1q21 was observed in one patient with hyperdiploid karyotype.

The FISH Panel revealed abnormality in 24 out of the 53(45%) patients and they were all correlated with the clinical status. Deletion 13q14 was detected in 9 patients; 3 patients had stable disease and 6 patients had advanced disease (4 deaths). Of note, these 6 patients presented the 13q14 deletion combined with 14q32 rearrangement. Chromosomal anomalies of 14q32 were observed in 13patients. Deletion of 17p13 was found in 5 patients and gain of 1q21 in 5 patients with advanced disease. Most the 29 patients (55%) with normal FISH Panel revealed stable disease.

In conclusion, our experience points to the use of this FISH Panel as a single, simple and useful tool for long term prognosis and survival prediction.