PERSISTENT DONOR CHIMERISM IS CONSISTENT WITH DISEASE-FREE SURVIVAL FOLLOWING BMT FOR CHRONIC MYELOID-LEUKEMIA

Chronic myeloid leukaemia (CML) can be treated successfully with allog eneic bone marrow transplantation (BMT) leading to long-term disease-f ree survival, Leukemia relapse, however, remains a significant clinica l problem, Relapse following BMT presumably results from the expansion of small numbers of recipient leukaemic cells which have survived the conditioning therapy, In order to define patients who are at a high r isk of leukaemia relapse, a variety of techniques have been employed t o detect persistence of host haemopoiesis (mixed chimaerism, MC) or re sidual leukaemia (minimal residual disease, MRD), However, the precise relationship between the detection of MC and MRD post-BMT is unknown, We have investigated chimaerism and MRD status in 22 patients who wer e in clinical and haematological remission post-allogeneic BMT for chr onic phase CML, Chimaerism was assessed using short tandem repeat PCR (STR-PCR) while BCR-ABL mRNA detection using reverse transcriptase pol ymerase chain reaction (RT-PCR) was performed to detect the presence o f MRD, Seventeen patients received unmanipulated marrow (non-TCD) whil e in five patients a T cell-depleted transplant (TCD) was performed as additional GVHD prophylaxis, Chimaerism was evaluated in 18 patients (14 non-TCD, four TCD), Mixed chimaerism was an uncommon finding in re cipients of unmanipulated BMT (21%) when compared to TCD BMT (100%), N o evidence of MRD, as identified using the BCR-ABL mRNA RT-PCR assay, was detected in those patients who were donor chimaeras, Early and tra nsient MC and MRD was detected in four patients (two non-TCD, two TCD) who have subsequently converted to a donor profile, One patient has s table low-level MC but remains MRD negative 4 years post-BMT, Late MC and MRD was observed in two patients who relapsed >6 years after TCD B MT for CML, We conclude that mixed chimaerism is a rare event in recip ients of unmanipulated BMT and that donor chimaerism as detected by ST R-PCR assay is consistant with disease-free survival and identifies pa tients with a low risk of leukaemic relapse post-BMT for CML.