Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: Remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients

Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clin ical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnose d cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases i ncluding 2 deaths, in contrast to the mild liver dysfunction in one third o f the relapsed patients. Forty of forty-seven (85.1%) relapsed patients ach ieved CR. Two of three nonresponders showed clonal evolution at relapse, wi th disappearance of t(15;17) and PML-RAR alpha fusion gene in 1 and shift t o a dominant AML-1-ETO population in another, suggesting a correlation betw een PML-RAR alpha. expression and therapeutic response. In a follow-up of 3 3 relapsed cases over 7 to 48 months, the estimated disease-free survival ( DFS) rates for 1 and 2 years were 63.6% and 41.6%, respectively, and the ac tual median DFS was 17 months. Patients with white blood cell (WBC) count b elow 10 x 10(9)/L at relapse had better survival than those with WBC count over 10 x 10(9)/L (P = .038). The duration of As2O3-induced CR was related to postremission therapy, because there was only 2 of 11 relapses in patien ts treated with As2O3 combined with chemotherapy, compared with 12 of 18 re lapses with As2O3 alone (P = .01). Reverse transcription polymerase chain r eaction (RT-PCR) analysis in both newly diagnosed and relapsed groups showe d long-term use of As2O3 could lead to a molecular remission in some patien ts. We thus recommend that ATRA be used as first choice for remission induc tion in newly diagnosed APL cases, whereas As2O3 can be either used as a re scue for relapsed cases or included into multidrug consolidation/maintenanc e clinical trials. (C) 1999 by The American Society of Hematology.