Deletion of the Short Arm of Chromosome 1 (del 1p) Is the Strongest Predictor of Poor Outcome in Myeloma Patients Undergoing an Autotransplant.

Background: Chromosomal abnormalities detected by conventional cytogenetic analysis are known to adversely impact the outcome in myeloma patients. Abnormalities of chromosome 1, 13, 14 and 17 are commonly described. Deletions of the short arm of chromosome 1 presumably result in a loss of tumor suppressor genes, including p73, a member of the p53 family. We report the outcome of 83 myeloma patients with clonal cytogenetic abnormalities who underwent high-dose therapy and single autologous stem cell transplantation at our institution.

Methods: We identified 83 patients (median age: 56 years) with clonal cytogenetic abnormalities detected at diagnosis by conventional chromosomal analysis. Patients underwent high-dose therapy and a single autologous transplant between April 2000 and May 2005. All 83 patients received high-dose melphalan, either alone (73) or as a combination of topotecan, melphalan and cyclophosphamide (TMC =10). Sixty-four patients were transplanted for the consolidation of first remission or for primary refractory disease, while 19 patients were transplanted for relapsed disease. The most common chromosomal abnormalities observed were hyperdiploidy (21%), del 1p (19%), 14q32 abnormalities (14%) and del 13q (10%).

Results: 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 del 1p (p= 0.001 and <0.0001, respectively), and those transplanted with relapsed disease (p= 0.03 and 0.04). Median PFS and OS for patient with del 1p were 12 and 22 months (vs. 26 moths and not reached for others), respectively. Thirty-two patients whose cytogenetic abnormalities resolved prior to autotransplant had a trend towards longer OS than the patients with persistent abnormalities (p = 0.08). Age, disease stage, β2m, serum albumin level, serum creatinine, and isolated abnormalities of chromosome 13q, 17 and 14 q32 did not emerge as significant predictors of outcome in this set of patients.

Conclusion: Del 1p is associated with a significantly shorter remission and survival in patients undergoing high-dose therapy and a single autologous transplant. Patients with this abnormality are candidates for novel therapeutic approaches including newer antimyeloma drugs and nonablative allogeneic transplantation.