IMPORTANCE OF MIXED CHIMERISM TO PREDICT RELAPSE IN PERSISTENTLY BCR ABL POSITIVE LONG SURVIVORS AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOID-LEUKEMIA/

Determination of hematological chimerism could be helpful in understan ding the biology of leukemic relapse after allogeneic bone marrow tran splant (BMT) for chronic myeloid leukemia (CML), because the detection of malignant residual cells carrying the bcr/abl message by qualitati ve RT-PCR is of limited value in predicting disease progression for in dividual patients. We have studied the chimerism pattern and the bcr/a bl status by Southern-blot in 15 CML patients (M/F:6/9) transplanted w ith unmanipulated BM from HLA identical sibling donors, persistently b cr/abl positive by RT-PCR. The median age of the series was 31 years ( 18-49) and disease status at BMT was: chronic phase: 11, accelerated p hase: 3 and blast crisis: 1 patient. Of the 15 patients, 9 are alive a nd in complete remission (CR), 4 have died in CR and 2 are alive but s uffered relapse at +19 and +26 months post-PMT. The median follow-up i s 81 months (13,7-168). Rearrangement of the BCR gene was performed by Southern-blot using P-32-labeled transprobe-1. PCR analysis of chimer ism was assessed using primers for the following VNTR loci: D1S80, D1S 111, 33.1, APO-B, YNZ-22, lambda g3 and DXS52. Seventy-nine samples we re analyzed (median per patient 5 (range 2-9)). Thirteen patients show ed complete chimerism and lacked BCR rearrangement over time by Southe rn-blot. The 2 patients who relapsed showed mixed chimera status from +9 and +5 months respectively until the end of the study. Persistent B CR rearrangement was observed in these 2 patients from +12 and +11 mon ths respectively. Our data suggest that mixed chimerism may predict he matologic or cytogenetic relapse by several months in those patients w ho are persistently PCR-positive post-BMT.