DETECTION OF MINIMAL RESIDUAL DISEASE IN PHILADELPHIA-CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC-LEUKEMIA - RATIONALE FOR BONE-MARROW TRANSPLANTATION FROM THE POLYMERASE CHAIN-REACTION POINT-OF-VIEW

Bone marrow transplantation (BMT) is performed as curative therapy for acute lymphoblastic leukemia (ALL). In most patients, BMT is performe d at the time of remission which implies that the number of leukemic c ells is less than 5% of all hematopoietic cells, namely, 0 to 10(10) l eukemia cells in the body. Thus, some patients may well undergo BMT de spite the fact that no leukemic cells are left in the body. In this re spect, more accurate diagnosis of complete remission status would be t o the patients' benefit. To detect minimal residual disease (MRD) not found by light-microscopy, further strategies are required after achie ving hematological remission. Cytogenetic methods, Southern blot analy sis and conventional immunological techniques can all provide accurate diagnosis, however, the sensitivity of these techniques for the detec tion of MRD is just as low as that of the light microscopy. Recently, polymerase chain reaction (PCR) has become. available for the detectio n of low levels of chimeric bcr-abl transcripts in Philadelphia chromo some positive (Phl) ALL patients. With this assay, investigators have reported MRD in patients after chemotherapy or BMT. Most patients who achieve hematological remission after conventional chemotherapy still have bcr-abl transcript detectable by PCR, confirming the general conc ept that this particular leukemia needs BMT in order to cure the disea se. Some patients who had MRD prior to BMT continued disease free surv ival > 1 year after BMT with a negative PCR result and in these patien ts, MRD seems to have been eradicated by the BMT procedure. Most patie nts with MRD still detectable after BMT, relapsed shortly after their first positive PCR result, indicating that PCR is a sensitive early ma rker of hematological relapse. Thus, PCR used for the detection of MRD seems useful for a more accurate assessment of remission status befor e and after BMT.