The Results of Molecular Relapses Treatment in Acute Promyelocytic Leukemia (APL) Patients.

Nearly all de novo APL patients (pts) undergo complete remission (CR) when treated with all- trans-retinoid acid (ATRA) plus chemotherapy. Nevertheless a significant portion (20%) of these pts ultimately relapse during the first 2 years of therapy. Minimal residual disease (MRD) monitoring using RT-PCR is widely recognized method for detection of molecular relapses (MR) in APL pts during hematological remission. However, the precise MR definition and significance of therapy changing when MR is detected are still controversial. We report the results of molecular monitoring and MR treatment in 40 pts (17 male, 23 female, median age = 33) who were included in the APL studies from 1997 to 2005. The induction and consolidation consisted of four 7+3+ATRA courses or four courses of 5 days Daunozome + ATRA or AIDA-protocol. Maintenance (MT) was performed for 2 years of CR with chemotherapy (5+2 courses) or chemotherapy combined with ATRA or monotherapy with ATRA+INF-alfa after Daunozome. RT-PCR for PML/RARα was performed on fresh marrow aspirates in all pts before treatment and periodically (2–3month) during 2 years after CR induction (2–18 investigations, median 6, for each pt). RT-PCR was performed using recommendations of BIOMED-1 Concerted Action (1999). MR was defined as probable if chimeric transcript was detected once and was not find out by second investigation and as proved when PML/RARA was detected at least twice by consecutive investigations (in 2–4 weeks). In case of proved MR we changed the type of MT. In pts with early MR (<12 mo of CR) MT was changed to Methotrexate+6-Mercaptopurine +ATRA. Pts with late MR (> 12 mo of CR) were treated with ATRA+IFN-α. After two hematological relapses (HR) in the group of probable MR we started to change the type of MT even if MRD was detected once. The Table 1 reflects the effect of MT changes on the frequency of HR in pts with MRs.

Our data shows the equal frequency of HR in pts with and without MR: 4/19 and 4/21. The absence of difference is probably due to the treatment changes in case of MR. We also can admit that ATRA monotherapy as maintenance is ineffective approach (3 MR and 3 HR). We revealed the statistically significant difference in the probability of hetmatological relapse in pts with MR in whom MT was changed (0 from 9 relapsed) and not changed (4 from 10 relapsed) (p= 0,04). So it seems reasonable that in proved and probable MRs MT should be changed. However, more investigations should be done for definition of the best postremission treatment strategy in APL pts with MRD.