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

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Abstract
Bone marrow transplantation (BMT) is performed as curative therapy for acute lymphoblastic leukemia (ALL). In most patients, BMT is performed at the time of remission which implies that the number of leukemic cells is less than 5% of all hematopoietic cells, namely, 0 to 10(10) leukemia cells in the body. Thus, some patients may well undergo BMT despite the fact that no leukemic cells are left in the body. In this respect, more accurate diagnosis of complete remission status would be to the patients' benefit. To detect minimal residual disease (MRD) not found by light-microscopy, further strategies are required after achieving hematological remission. Cytogenetic methods, Southern blot analysis and conventional immunological techniques can all provide accurate diagnosis, however, the sensitivity of these techniques for the detection of MRD is just as low as that of the light microscopy. Recently, polymerase chain reaction (PCR) has become available for the detection of low levels of chimeric bcr-abl transcripts in Philadelphia chromosome positive (Ph1) 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 concept that this particular leukemia needs BMT in order to cure the disease. Some patients who had MRD prior to BMT continued disease free survival > 1 year after BMT with a negative PCR result and in these patients, MRD seems to have been eradicated by the BMT procedure.(ABSTRACT TRUNCATED AT 250 WORDS)