The detection of contaminating clonal cells in apheresis products is related to response and outcome in multiple myeloma undergoing autologous peripheral blood stem cell transplantation

In the present paper, we report on the use of the heteroduplex PCR techniqu e to detect the presence of clonally rearranged VDJ segments of the heavy c hain immunoglobulin gene (VDJH) in the apheresis products of patients with multiple myeloma (MM) undergoing autologous peripheral blood stem cell (APB SC) transplantation. Twenty-three out of 31 MM patients undergoing APBSC tr ansplantation with VDJH segments clonally rearranged detected at diagnosis were included in the study. Samples of the apheresis products were PCR ampl ified using J(H) and V-H (FRIII and FRII) consensus primers and subsequentl y analyzed with the heteroduplex technique, and compared with those obtaine d at diagnosis. 52% of cases yielded positive results (presence of clonally rearranged VDJH segments in at least one apheresis), The presence of posit ive results in the apheresis products was not related to any pretransplant characteristics with the exception of response status at transplant. Thus, while no one patient with positive apheresis products was in complete remis sion (CR), negative immunofixation, before the transplant, five cases (46%) with negative apheresis were already in CR at transplant (P = 0.01). The r emaining six cases with heteroduplex PCR negative apheresis were in partial remission before transplant. Patients with clonally free products were mor e likely to obtain CR following transplant (64% vs 17%, P = 0.02) and a lon ger progression-free survival, (40 months in patients transplanted with pol yclonal products vs 20 with monoclonal ones, P = 0.03). These results were consistent when the overall survival was considered, since it was better in those patients with negative apheresis than it was in those with positive (83% vs 36% at 5 years from diagnosis, P = 0.01), These findings indicate t hat the presence of clonality rearranged VDJH segments is related to the re sponse and outcome in MM transplanted patients.