MOLECULAR MONITORING OF MINIMAL RESIDUAL DISEASE IN FOLLICULAR AND MANTLE CELL NON-HODGKINS-LYMPHOMAS TREATED WITH HIGH-DOSE CHEMOTHERAPY AND PERIPHERAL-BLOOD PROGENITOR-CELL AUTOGRAFTING

Minimal residual disease (MRD) was evaluated in 30 patients with folli cular or mantle cell non-Hodgkin's lymphoma (NHL) undergoing an intens ive treatment with high-dose sequential (HDS) chemotherapy and periphe ral blood progenitor cell (PBPC) autografting. To minimize the potenti al tumor cell contamination, PBPC harvests were scheduled at the end o f HDS pretransplant phase. All patients had advanced-stage disease and most of them presented with bone marrow (BM) involvement. A tumor mar ker could be generated in 90% of patients using bcl-2 or Ig heavy-chai n genes. MRD was analyzed on PBPC, BM harvests, and after autografting by polymerase chain reaction (PCR). All evaluable follicular and 6 of 9 mantle cell patients achieved clinical complete remission. PCR nega tivity of PBPC and/or BM harvests was documented in 68% of follicular and 12% of mantle cell lymphomas. Molecular remission of PBPC and/or B M harvests was achieved in 9 of 15 patients with overt marrow involvem ent and in all patients with only molecular marrow infiltration at ons et. Molecular follow-up was conducted on 14 patients: all 7 evaluable patients who received at least one PCR-negative graft maintained the n egative status at a median follow-up of 24 months and none of them rel apsed so far. Thus, the results show that (1) a molecular marker to mo nitor MRD can be obtained in most follicular and mantle cell NHL patie nts, (2) the HDS regimen may provide PCR-negative PBPC and/or BM harve sts even from patients with BM disease, and (3) autograft with at leas t one PCR-negative harvest is associated with a durable clinical and m olecular remission. (C) 1997 by The American Society of Hematology.