An understanding of laboratory monitoring is predicated on an appreciation of therapeutic goals and options. The goal of therapy is to eliminate disease; however, if eradication of the neoplastic clone cannot be achieved then therapeutic intent relies on tumor control with an attempt to forestall disease progression.
Molecular monitoring with qualitative RT-PCR originated in the posttransplantation setting. Here it serves two distinct functions: first to document remission and then to monitor for disease relapse. In the latter, molecular monitoring permits early disease detection (prior to hematological or cytogenetic manifestations), when the tumor burden is low and presumably more amenable to treatment. At molecular relapse, therapeutic options include the withdrawal of immunosuppressive agents and/or the administration of donor lymphocyte infusions (DLI) with an improved response when implemented prior to overt hematological relapse.
Therapeutic context dictates the ramifications of any test result. In the setting of ASCT, the interval post-transplant, the type of transplant (i.e., unrelated vs. allogeneic-related matched), and the presence or absence of T-cell depletion may all impact the prognostic relevance of qualitative test results. Most patients are qualitatively RT-PCR positive in the first 6 months following ASCT and such results are thus of little consequence. Six to 12 months after ASCT, however, positive qualitative results are highly predictive of subsequent relapse.[14,15] Here RT-PCR positiv-ity precedes cytogenetic and hematological relapse by several months.
Although qualitative RT-PCR has been the mainstay of minimal residual disease assessment, a single positive qualitative result is, in isolation, of little clinical predictive value. In contrast, quantitative RT-PCR shows broad relevance to posttherapeutic monitoring whether after transplantation or other therapeutic modalities. Logically, low or falling transcript levels correlate with successful treatment or continued remission, and elevated or rising transcript levels predict relapse. Consequently, quantitative RT-PCR has emerged as the preferred modality for posttherapeutic monitoring.
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