Pretransplantation Burden of Leukemic Progenitor Cells as a Predictor of Relapse after Bone Marrow Transplantation for Acute Lymphoblastic Leukemia

Abstract

Background. We developed a test to discern small numbers of residual leukemic progenitor cells in the bone marrow of patients with acute lymphoblastic leukemia (ALL) in remission. Preliminary studies revealed that before undergoing bone marrow transplantation such patients differed in their burden of leukemic progenitor cells. These observations suggested that the burden of these cells might influence the risk of relapse after transplantation. Methods. The number of residual leukemic progenitor cells before bone marrow transplantation was determined for 83 patients with high-risk ALL. We combined multiparameter flow cytometry and cell sorting with assays for leukemic progenitor cells in a quantitative method for the detection of minimal residual disease. Results. The count of leukemic progenitor cells in bone marrow specimens from patients in remission varied markedly between patients, ranging from O to 12,546 cells per million mononuclear cells, or from O to 1.255 percent (median, 51 leukemic progenitor cells per million mononuclear cells, or 0.005 percent). Patients whose count of leukemic progenitor cells exceeded the median value had a higher likelihood of relapse than did patients with values below the median (relapse rate at one year, 100 percent vs. 41 percent; P<0.001). There was a statistically significant inverse relation between the leukemic progenitor-cell content of bone marrow before transplantation and the duration of remission after transplantation (P<0.001 ). The estimated risk of relapse for patients with ≥51 leukemic progenitor cells per million mononuclear cells was more than 3.5 times the risk for patients with lower counts, after adjustment for the effects of other covariates (P = 0.005). Conclusions. The count of residual leukemic progenitor cells is a powerful predictor of relapse after autologous bone marrow transplantation, particularly among male patients. Its measurement may be useful for analyzing and improving the treatment of patients with high-risk ALL in remission.