Is flow cytometric DNA content hypodiploidy prognostic in multiple myeloma?

Hypodiploid multiple myeloma is uncommon when assessed by DNA content flow cytometry, having been reported in less than 6% of patients with newly diagnosed multiple myeloma. Previous studies have shown these patients to be unresponsive to therapy and to have short survival. To address this further, we studied 349 of 504 patients eligible for Eastern Cooperative Oncology Group (ECOG) treatment trial E9486 and laboratory correlative study E9487 who had marrow mononuclear cells available for ploidy analysis. Marrow samples were studied by dual channel flow cytometry, using propidium iodide to measure the DNA content and kappa and lambda light chain antisera to identify the clonal cells. A DNA index < 0.95 was considered hypodiploid. Five patients (1.4%) were found to have hypodiploid DNA content in their marrow plasma cells. Three of the 5 patients with hypodiploid myeloma had a partial objective response to chemotherapy, which is not different from the overall objective response rate for all patients enrolled on E9486. All five patients with hypodiploid multiple myeloma died within 4 years from diagnosis, but these patients had a similar overall median survival (2.6 years) compared to the patients with diploid DNA content. Our studies confirm the poorer survival of patients with diploid versus hyperdiploid myeloma; we cannot confirm, however, the previously reported very poor outcome associated with hypodiploid myeloma using DNA content flow cytometry. Hypodiploid DNA content of plasma cells by flow cytometry may not be as ominous a factor as previously reported.