Influence of Residual Normal Metaphases In Patients with Monosomal Karyotype.

Abstract 1671

Breems et al.(J Clin Oncol 2008;26:4791-97) observed that a monosomal karyotype(MK: ≥ 3 cells with ≥2 autosomal monosomies or with 1 autosomal monosomy plus a structural abnormality) conveyed a worse prognosis in untreated AML than a complex karyotype (CC ≥ 4 distinct clonal abnormalities),although there was considerable overlap between MK and CC. The SWOG (Medeiros et al. Blood e pub June, 2010) has confirmed these findings and extended them to patients age 60 or above. Previous data (Estey et al. Haematologica 2000;85:246-49) suggested that the presence of residual normal cells improved prognosis in patients with monosomy 7, prompting us to see if the same was true in patients with MK. Our analysis focused on survival and used the same 176 MK patients identified by Mederios et al. from 1,344 patients enrolled in one of 10 successive SWOG clinical trials. The MK patients had a median age of 61 years and 94% had a CC (≥ 3 distinct clonal abnormalities); 68% received induction with standard dose ara-C, 14% with other ara-C doses, and 18% without ara-C. A univariate proportional hazards model indicated that survival improved as the % of normal cells increased and accordingly as the % of abnormal cells (MK and non MK) decreased. Further investigation indicated that this reflected the number of normal, rather than the number of abnormal, cells. Thus having one or more normal cells was associated with a hazard ratio (HR) of 0.95 (p = 0.02), while the presence of 5 or more normal cells decreased the HR to 0.76. In contrast, there was no association between the number of abnormal MK cells and survival (p=0.15). Accounting for age and treatment (as noted above) did not alter these conclusions (HR for having 1 or more normal cells 0.95, p = 0.03).Despite the p-values these findings have limited medical significance for MK patients; since even the aforementioned decrease in HR to 0.76 would result in a median survival of only 5.3 months vs. the median of 4 months for all 176 MK patients. Nonetheless the results indicate that it might be worthwhile to examine the prognostic effect of residual normal metaphases in patients with better prognosis karyotypes.