Therapeutic Monitoring

APL patients who enter morphologic complete remission (CR) after a single round of induction therapy will often be reverse transcriptase polymerase chain reaction (RT-PCR) positive, and a small minority will have low numbers of residual abnormal promyelocytes. In general, neither finding indicates failure of induction therapy, and such patients should proceed promptly to consolidation. However, a positive RT-PCR result at the end of consolidation, at least in patients treated according to the Italian consolidation regimen, seems to indicate treatment failure.14 In the Italian study, among 23 patients (out of 683) who were RT-PCR positive at the end of consolidation, 7 were treated "preemptively" with salvage therapy and stem cell transplant, while treatment was delayed in the remaining 16 until development of hematologic relapse. All seven patients treated early (i.e., with persistent molecular disease) were alive, compared to only 2 of the 16 patients treated at the time of hematologic relapse.14 After consolidation, APL patients who are RT-PCR negative should undergo routine molecular monitoring (e.g., every 2-4 months for at least 2 years) to detect incipient relapse.1516 As is discussed below in depth, two successive positive RT-PCR assays (at a sensitivity of 1 in 104) are highly predictive of subsequent hematologic relapse and cannot be ignored. It is currently not known if blood can substitute for bone marrow for the RT-PCR assays; therefore, bone marrow is the preferred source for collection of cells and isolation of mRNA. A single negative RT-PCR assay has little clinical significance in APL, even at the end of consolidation, and serial monitoring is key to early detection of relapse. Finally, while quantitative RT-PCR assays have been developed and are undergoing clinical test-ing,1718 qualitative RT-PCR assays at a sensitivity of 1 in 104 remain the "gold standard" for detection of minimal residual disease, and clinicians caring for APL patients need access to a reliable laboratory that can provide this type of serial molecular monitoring.

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