Loss of Chromosome 1p21 Band Is Associated with Disease Progression and Poor Survival in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

Amplifications involving chromosome 1q and deletions involving 1p are frequent events in multiple myeloma (MM). The pathogenesis and clinical significance of these anomalies are largely unknown. As karyotyping and SNP based mapping analysis identify a minimal common deletion region involving the 1p21 locus, we investigated the prevalence and prognostic significance of del(1p21) in a cohort of 235 MM patients undergoing highdose therapy and autologous stem cell transplant at our institution. Fluorescence in situ hybridization combined with cytoplasmic light chain detection (cIg-FISH) was used to evaluate clonal plasma cells for 1p21 deletion as well as other myeloma-associated chromosomal abnormalities. In addition, 1p21 status was evaluated in 16 patients with of monoclonal gammopathy of undetermined significance (MGUS) and 41 patients with plasma cell leukemia (PCL). CIg-FISH detected hemizygous 1p21 deletions in 18% of the MM, 34% of PCL but none of the MGUS cases. In MM, the median percentage of clonal plasma cells harboring del(1p21) was 55% (range 20–95%). The presence of 1p21 deletions was strongly correlated with 1q21amplification (p=0.01), and marginally correlated with del(p53) (p=0.05) or t(4;14) (p= 0.06), but not with del(13q) or t(11;14). There was no association between del (1p21) and other biological factors including age, gender, Hb, albumin, C-reactive protein, beta-2 microglobulin level, isotype or bone marrow plasmacytosis. The median follow-up in this cohort was 36 months. Patients with 1p21 deletions had significantly shorter progression-free (median 14.2 vs. 25.4 months, p<0.001) and overall survivals (median 39.4 vs. 82.3 months, p=0.001) than those without such deletions. In multivariate analysis, del(1p21) was an independent risk factor for progression free (p= 0.003) and overall survivals (p=0.013) after adjusting for del(13q), del(p53), t(4;14) and 1q21 amplification. 1q21 amplification was significant risk factor in univariant analysis for either progression-free or overall survivals, but did not remain as an independent risk factor in multivariant model adjusting for other genetic risk factors. Our results indicate that del(1p21) is an independent poor prognostic factor associated with disease progression in MM. We recommend include this genetic aberration as part of a routine work-up in the risk-stratification of MM patients receiving autologous stem cell transplantation.