EVALUATION OF MINIMAL RESIDUAL DISEASE IN HIGH-RISK CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA USING AN IMMUNOLOGICAL APPROACH DURING COMPLETE REMISSION

Background. Sensitive methods for detecting residual disease may compl ement conventional morphology while monitoring the response to treatme nt in leukemia patients. Methods. We studied minimal residual disease (MRD) by selecting via a colony assay a peripheral blood (PB) cell pop ulation enriched in putative malignant cells and detecting occult leuk emic cells by double immunologic analysis performed on colonyforming c ells (CFC). Using this combined technique we assayed the PB of high ri sk children with acute lymphoblastic leukemia (ALL) in order to demons trate possible differences in <<the residual tumor cell burden>> among leukemia patients and to correlate these with a 3-year clinical follo w-up. Results. In all 22 patients positive results were obtained for u p to 18 months following induction chemotherapy at times of apparent h ematologic remission. Common ALL (cALL) patients exhibited a mean of 9 .6% cAlla+ cells (range: 2% to 30%), whereas cALL antigen (cALLA) and cALLA/Tdt or CDla/Tdt combination were never found in the colonies der ived from healthy individuals. Six out of 22 cALL patients expressed a mean of 16.5% cALLA+/Tdt+ CFC (range: 2% to 35%). Five TALL children presented a mean of 24% CD1a/Tdt+ cells (range: 8% to 44%). Extensive follow-up indicates a correlation between the percentage of CFC Tdt+/l ymphoid marker+ cells (more than 10%) and subsequent clinical relapse. In one patient relapse occurred after 16 months with a dramatic incre ase in the number of leukemic cells. In contrast, the decline in malig nant cells, observed in two cases, predicted a favourable course. Five patients tested before autologous bone marrow transplantation (ABMT) presented high number of positive cells and relapsed at various times. Conclusions. We conclude that this approach to the study of MRD could be valuable in monitoring the efficacy of chemotherapy, as well in ev aluating the quality of purged marrow.