Unique role of cytogenetics in the prognosis of patients with myeloma receiving high-dose therapy and autotransplants.

Abstract

PURPOSE Although important predictors of survival in myeloma patients have been identified, it is well recognized that better prognostic factors for this disease are needed. Because cytogenetics play a dominant role in the outcome of patients with acute leukemia, their prognostic value was evaluated in a large group of newly diagnosed and previously treated myeloma patients receiving autotransplants. METHODS A total of 427 either newly diagnosed (26%) or previously treated patients (74%) received tandem transplants, supported by mobilized peripheral-blood stem cells. Numerous variables, including cytogenetics, were analyzed for their impact on complete remission, event-free survival (EFS), and overall survival (OS). RESULTS Abnormal karyotypes were detected in 37% of our patients and were very complex, irrespective of the duration of standard therapy before the first autotransplant. In addition to previously recognized unfavorable implications of partial or complete deletion of chromosome 13 and 11q abnormalities, we now observed that the presence of any translocation likewise portended poor outcome (unfavorable karyotypes). On multivariate analysis, the absence of an unfavorable karyotype was the most favorable variable for both EFS (P = .0001) and OS (P = .0001). Other favorable factors were duration of standard therapy and a low beta-2 microglobulin (B2M) level before the first autotransplant. A risk-based classification system was developed according to the number of these favorable variables present, showing highly significant differences in event-free and overall survival. CONCLUSION Cytogenetics play a dominant role in myeloma and were independent of previously recognized important prognostic factors, such as B2M and duration of prior standard therapy.