Dynamic of morphologic and molecular remission in patients (pts) with APL treated with frontline ATRA and arsenic trioxide (ATO).

Abstract

6548 Background: APL is associated almost in all pts with t (15; 17) (q21; q22) leading to the fusion gene PML-RARα which can be identified by reverse transcriptase polymerase chain reaction (RT-PCR). Minimal residual disease (MRD) monitoring based on the detection of PML-RARα transcripts by PCR technology has a well-demonstrated role in APL. Purpose: To describe the dynamics of response in pts with APL on our frontline study of ATRA and ATO. Methods: From February 2002 to January 2010, 111 pts with newly diagnosed APL have been treated with ATRA plus ATO. The first cohort of 65 pts received ATRA and ATO (beginning on day 10 of ATRA). High risk pts (WBC > 10 x 109/L) received GO (gemtuzumab) on the first day. The second cohort of 46 pts (38 evaluable pts) received ATRA and ATO concomitantly on day one. They also received GO on day one, if high risk, and if their WBC increased to more than 30 x 109/L during induction. Quantitative PCR (Q-PCR) for PML-RARα fusion gene was conducted after induction and throughout consolidation and follow up for the latter cohort. Results: The median time (range) to CR was 29 days (19-70) in the first cohort, 29 days (25-73) in the second cohort; the median time to complete molecular response (CMR) was 117.5 days (26-323) in the first cohort, was 101.5 days (25-240) in the second cohort. There was no difference of time to CMR between two cohorts (p = 0.15). Three pts in the first and 2 pts in the second cohort have relapsed, all having previously achieved CMR. Two pts with CNS relapse remained PCR-negative at the time of relapse. All other relapsed pts had positive peripheral blood (PB) or bone marrow (BM) PCR tests prior to relapse. There was strong correlation (Spearman correlation: 0. 86, p < 0.0001) between PB and BM Q-PCR on 75 concomitant samples (within 1 day of each other) from 25 pts; no significant difference between BM and PB (p = 0.76, paired Wilcoxon test). Conclusions: There was no significant difference between ATO at day 1 of ATRA or day 10 regarding time to CR and time to CMR. Relapse occurred in 5% and was preceded by a positive PCR except for CNS relapse. Among the available paired samples there is a strong correlation between BM and PB PCR suggesting that PB may be used to monitor pts for impending relapse. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cepahlon Cepahlon