Cytogenetic Profile Of Multiple Myeloma In The Inner City: Clinical Presentation and Survival

Multiple Myeloma (MM), a plasma-cell neoplasia characterized by bone marrow (BM) infiltration, monoclonal protein production, and end organ dysfunction, is the most common hematologic neoplasm in blacks. The subclinical syndrome monoclonal gammopathy of undetermined significance (MGUS) precedes MM, and SEER data as well as more recent reports show that blacks have a 2-3-fold higher risk of developing MGUS and MM suggesting a genetic predisposition that causes the marked racial disparity in the incidence of both conditions. In addition, the recent rate of survival improvement observed in Caucasian patients has not been observed in blacks implying that the clinical course and development of resistance are varied between black and Caucasian MM patients. We have recently reported that in our inner-city, largely Caribbean-African patients MM occurs more frequently in women and at a younger age compared to literature. In this report we present cytogenetic information on 146 of these newly-diagnosed MM patients and their survival data.

Patients were identified by tumor registries at UH and Kings County Hospital based on tumor histopathology. Data were collected from hospital records of patients treated between 2001-2011 (n=242).Downstate’s inner-city MM patients in Brooklyn, NY are largely Caribbean-African individuals and descendants. Demographics, disease indicators, and vital statistics were collected. In 146 patients, baseline cytogenetics by chromosome banding studies were available. In 63 of these patients baseline FISH used locus-specific probes del13 (13q14), IGH translocation (14q32), del17 and t(11;14)(q13;q32). Patients were treated with standard combination therapies.

146 patients had active, advanced newly-diagnosed MM. Median age=66 (range 36-91), male/female= 0.8, and evidence for the degree of tumor burden included: median % infiltration with CD138-positive cells within BM=50% (range 7%-99%), median serum M protein 3.3 g/dL (range 0.2-9.1). International Staging System level: Stage II: 28%, Stage III: 72%; median serum creatinine=2 mg/dL (range 0.38-14), median serum beta-2 microglobulin= 5.8 mg/dl (range 0.96-20.2). Further, 58% of patients with cytogenetic information had diffuse skeletal involvement with multiple lytic lesions (48%) and fractures (10%). Contrary to expectations from patients with advanced MM, chromosome banding and FISH showed abnormal cytogenetics (AC) in only 26% (n=38). At present, 50% of the patients have expired in both the normal cytogenetics (NC) and AC groups. In the AC group who expired, average time with MM was 2 years (range 0.5-5.6), whereas in the NC patients, average survival was 3.4 years (range, 0.6-5.2). Frequency of trisomies 5 and 9 indicative of hyperdiploidy, were twice as common in patients who are surviving with AC. In these latter patients as well as in surviving patients with NC, average survival time with MM is 4 years (range 0.4-15). In addition, IGH translocation was twice as common in AC patients who expired compared to the NC group. Other AC findings including hypodiploidy, del13, chr1 loss, and trisomies involving chromosomes 1, 7, 11, 19, and 21 were equally frequent in expired and living patients with AC.

Using clinically available methods we found IGH translocation, trisomy 5 and trisomy 9 to be prognostically significant in this cohort of 145 inner-city, largely Carribean-African patients. Subtle presentation of cytogenetic abnormalities suggest that genome-wide analyses are needed to asses this patient populations’ MM biology.