Molecular and clinical remissions in multiple myeloma: Role of autologous and allogeneic transplantation of hematopoietic cells

Purpose: To describe molecular monitoring of minimal residual disease in pa tients with myeloma who have achieved complete remission (CR) after autolog ous or allogeneic transplantation of hematopoietic cells. Materials and Methods: Clonal markers based upon the rearrangement of immun oglobulin heavy-chain genes were generated for each patient and used for po lymerase chain reaction (PCR) defection of residual myeloma cells. Fifty-on e patients entered the program and 36 achieved CR. After transplantation, m olecular monitoring was performed on 29 patients (15 autologous and 14 allo geneic transplants) who had molecular markers. Results: Our data show that molecular remissions are rarely achieved (7%) w ith high-dose chemotherapy followed by single or double autografting. In ad dition, virtually all peripheral blood progenitor cell and bone marrow samp les contained residual myeloma cells, even when sample collection was sched uled after repeated courses of high-dose chemotherapy. All patients autogra fted with PCR-positive cells remain positive, and eight of 15 have relapsed . Two patients were autografted with PCR-negative cells: one is in clinical and molecular remission, and one relapsed 25 months after the transplant. In the allografting setting, a higher proportion of patients (50%) achieved molecular remission; there were two relapses, one in the PCR-positive grou p and one in the PCR-negative group. Conclusion: This is the first large study of molecular remissions in myelom a patients to use a PCR-based approach utilizing patient-specific tumor mar kers, The sizeable fraction of patients who achieved molecular remission af ter allografting with peripheral blood progenitor cells represents a promis ing finding in an incurable disease. J Clin Oncol 17:208-215, (C) 1999 by American Society of Clinical Oncology.