SEQUENTIAL MOLECULAR MONITORING OF CHIMERISM IN CHRONIC MYELOID-LEUKEMIA PATIENTS RECEIVING DONOR LYMPHOCYTE TRANSFUSION FOR RELAPSE AFTER BONE-MARROW TRANSPLANTATION

Recent observations of chimerism in patients relapsed following an all otransplant suggest the persistence of immunotolerance, thus offering a biologic rationale for the use of donor lymphocyte transfusion (DLT) , In this study, we have analyzed by PCR amplification of several VNTR regions, sequential bone marrow and peripheral blood DNA samples in f our patients who received DLT for CR IL relapse after bone marrow tran splantation. Prior to DLT, all patients showed mixed chimerism in peri pheral blood cells while two had mixed chimerism and two no chimerism in the PM, None of these four patients showed evidence of chimerism at the cytogenetic level (all had 100% +ve metaphases), After DLT, a com plete hematologic and molecular remission (ie disappearance of the BCR /ABL fusion transcript) was obtained in the two patients who had bone marrow mixed chimerism prior to DLT, The two patients without evidence of marrow chimerism prior to DLT converted to a pattern of mixed chim erism after DLT, but both developed a severe bone marrow aplasia occur ring at day 56 and 36, respectively, With regard to the sequential ana lysis of bone marrow chimerism after DLT we observed that: (1) the dis appearance of BCR/ABL +ve cells paralleled the conversion to a pattern of full donor chimerism; and (2) the time interval to achieve CR was inversely correlated with the percentage of donor DNA in bone marrow, In conclusion, we have shown here that the assessment of bone marrow p re-DLT chimerism by PCR analysis might predict the response in patient s with favorable characteristics, and also might identify patients at high risk of developing severe myelosuppression.