Deletion of the Short Arm of Chromosome 1 (del 1p) is a Strong Predictor of Poor Outcome in Myeloma Patients Undergoing an Autotransplant

Abstract

Several chromosomal abnormalities detected by conventional cytogenetic analysis have an adverse impact on the outcome in myeloma patients. A wide spectrum of abnormalities involving chromosomes 1, 13, 14, and 17 has been described. We analyzed the outcome of 83 patients with clonal cytogenetic abnormalities, who underwent high-dose therapy and autologous stem cell transplantation for multiple myeloma at our institution. Clonal abnormalities were detected at diagnosis by conventional cytogenetic analysis in 83 patients. Patients underwent a single autologous transplant between April 2000 and May 2005. Preparative regimen was high-dose melphalan alone (73), or a combination of topotecan, melphalan, and cyclophosphamide (TMC=10). The most commonly observed chromosomal abnormalities were deletion of chromosome 13 (32%), hyperdiploidy (21%), deletion of chromosome 1p (18%), and t (11; 14) in 7% patients. Median follow-up among surviving patients was 25.5 months. Median interval from diagnosis to autotransplant was 7.7 months (range: 2.5-52). Median progression-free survival (PFS) for the entire group was 19 months and the median overall survival (OS) was 52 months. On univariate analysis, both PFS and OS were significantly shorter in patients with deletion 1p (P=.001 and <.0001, respectively). Thirty-two patients whose cytogenetic abnormalities returned to normal prior to autotransplant had longer PFS and OS than patients with persistent abnormalities (P=.02 and .08, respectively). Deletion 1p is associated with a significantly shorter remission and survival in patients undergoing high-dose therapy and a single autologous transplant for myeloma.

Molecular cytogenetic evaluation of the mechanism of micronuclei formation induced by camptothecin, topotecan, and irinotecan

“…confirms the aneugenic effect of topotecan containing regimens in vivo reported by Qazilbash et al [2007], where in bone marrow from cancer patients, an increase in the hyperdiploidy and deletion of chromosome 13, using Gbanding technique, was observed. Of the signal-positive MN, 45 (56.9%) had one signal, 24 (30.4%) contained two signals, and 10 (12.7%) had 3 signals.…”

Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients

“…In a work by Walker et al 12 , the incidence of deletion 1p rose to 30% (24% in the work of Avet-Loiseau et al 11 ). In 2007, Giralt 14 et al identified deletion 1p in 18% of patients and found an association with a significantly shorter PFS and OS. Boyd et al 13 have published a study of deletions at 1p12, 1p22 and 1p32 where del(1p32) was present in 11.3% of patients and impaired survival (34.5 months versus not reached, p<0.001) and 1p22 did not affect survival although it was the most frequently deleted region (22.5%).…”

An update on molecular biology and drug resistance mechanisms of multiple myeloma

“…Most of the structural aberrations in MM occur in chromosome 1. Deletions generally involve in 1p whereas amplifications correspond to 1q (Le Baccon et al, 2001;Qazilbash et al, 2007).…”