SIGNIFICANCE OF MOLECULAR MARKER-POSITIVE CELLS AFTER AUTOLOGOUS PERIPHERAL-BLOOD STEM-CELL TRANSPLANTATION FOR NON-HODGKINS-LYMPHOMA

Purpose: To evaluate the significance of molecular marker-positive cel ls in a cohort of non-Hodgkin's lymphoma (NHL) patients undergoing hig h-dose chemotherapy and autologous peripheral-blood stem-cell transpla ntation (PBSCT). Patients and Methods: Twenty-eight PBSC transplants h ave been performed in 24 patients with poor-prognosis NHL. Molecular a nalysis of the t(14; 18) (q32;q21) translocation (bcl-2/immunoglobulin [Ig] heavy-chain joining locus [JH] fusion) or antigen receptor gene rearrangements was performed to determine the presence of lymphoma cel ls at presentation, in PBSC harvests, and before and after autologous PBSCT. Kaplan-Meier estimates of survival and Cox regression analyses were used to test the effect of bone marrow involvement, tumor-cell co ntamination of PBSCs, disease stage, and chemotherapy sensitivity and transplantation, and presence of marker-positive cells post-PBSCT on d isease-free and overall survival. Results: Thirteen of 24 patients (54 %) are alive following PBSCT at a median follow-up time of 654 days (r ange, 193 to 1,908). Nine patients are in complete remission (CR) at d ay 216 to 1,799 (median, 805) and four are alive following relapse (da y 440, 573, 1,188, and 1,908). Eleven patients (46%) have died: three of transplant-related complications at day 0, 1, and 13, and eight of recurrent disease (day 132 to 1,330; median, 451). Longitudinal marker studies post-PBSCT showed that of 16 relapse events, 13 (81%) were po sitive for the lymphoma marker at or before clinically documented rela pse. Marker studies became negative post-PBSCT in nine of nine patient s who entered and remained in CR. Disease-free survival (DFS) was sign ificantly shortened in patients in whom marker-positive cells were det ected in serial samples posttransplantation (P = .006). Cox regression analysis showed that patients in this group had a 24 times higher ris k of relapse (P = .03). Conclusion: The results show that the reappear ance or persistence of marker-positive cells after autologous PBSCT is strongly associated with relapse.