Prospective monitoring of minimal residual disease in acute myeloid leukemia with inversion(16) by CBF beta/MYH11 RT-PCR: Implications for a monitoring schedule and for treatment decisions

Minimal residual disease in patients with acute myeloid leukemia (AML) with inversion(16) can be monitored by CBF beta /MYH11 RT-PCR. While the associ ation between molecular remission (MR) in bone marrow (BM) and peripheral b lood (PB) and long-term clinical remission (CR) seems to be established, th ere are insufficient data on the kinetics of CBF beta /MYH11. We have perfo rmed a prospective study in order to generate a reasonable and sufficient s chedule for PCR-monitoring. I I patients with AML and inversion (16) in com plete hematological remission have been prospectively monitored by CBF beta /MYH11 RT-PCR in their BM and PB during an observation period of 7 to 67 m onths (median 32 months). Patients were followed during consolidation chemo therapy with repetitive cycles of high-dose Ara-C and after autologous or a llogeneic stem cell transplantation in 2(nd) CR or refractory AML. MR never coincided with achievement of CR but occurred between 2 and 8 months after hematological remission. All patients in continuous CR were PCR- negative after 1-8 (median 4) months. Two patients relapsed despite MR for 10 to 15 months. Molecular relapse preceded hematological relapse by 3 to 5 months. Three out of four patients who were not in MR after 8 months relapsed. Allo geneic stem cell transplantation was able to eradicate minimal residual dis ease in 4/4 patients. In 2 patients a temporary reconversion to PCR-positiv ity was reversed by reduction of immunosuppression. I patient did not becom e PCR-negative until compete withdrawal of immunosuppression. We suggest th at BM and PB should be examined after the last consolidation treatment. In case of MR, PB should be examined every I to 2 months and BM examination sh ould be done only in case of PCR-positivity in PB in order to confirm the m olecular relapse and to identify an impending cytogenetic and/or hematologi cal relapse. CBF beta /MYH11 RT-PCR monitoring is able to predict relapse 3 to 5 months prior to overt hematological relapse, offers a window of oppor tunity for preemptive therapy of molecular relapse and confers implications for immunotherapy in the setting of allografting.