LITTLE EVIDENCE FOR CLONAL EVOLUTION OF MALIGNANT HEMATOPOIETIC-CELLSFOLLOWING RELAPSE AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION

By screening for immunoglobulin (Ig) and T-cell receptor (TCR) gene re arrangements in bone marrow samples aspirated at different time points during the course of disease from 43 patients with acute leukaemia we have analysed the extent of clonal evolution after autologous bone ma rrow transplantation (ABMT) and addressed the issue of whether the Sou thern Blot method has the bower to reveal clonal proliferations repres enting minimal residual disease (MRD) in the autologous bone marrow gr afts. Our results show that no clonal proliferations were detectable i n any of the 43 bone marrow grafts analysed, even after we analysed DN A preparations in 5 cases from cells highly enriched for cells of the original malignant immunophenotype. Moreover, as judged by the Ig- and TCR gene configurations in Il patients, relapse arose from the origin al clone even though minor clonal variations did occur in about half o f the relapsing patients. We conclude that while the Southern Blot met hod can detect gene receptor rearrangements in the majority of patient s with acute leukaemias and high-grade non-Hodgkins lymphomas, it is n ot useful for predicting relapse after ABMT. On the other hand, it is possible - by employing it - to evaluate whether or not relapse after ABMT arises from the original malignant clone and to what extent clona l evolution has taken place.