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

Abstract

Fifty-eight acute promyelocytic leukemia (APL) patients (11 newly diagnosed and 47 relapsed) were studied for arsenic trioxide (As2O3) treatment. Clinical complete remission (CR) was obtained in 8 of 11 (72.7%) newly diagnosed cases. However, As2O3 treatment resulted in hepatic toxicity in 7 cases including 2 deaths, in contrast to the mild liver dysfunction in one third of the relapsed patients. Forty of forty-seven (85.1%) relapsed patients achieved CR. Two of three nonresponders showed clonal evolution at relapse, with disappearance of t(15;17) and PML-RAR fusion gene in 1 and shift to a dominant AML-1-ETO population in another, suggesting a correlation between PML-RAR expression and therapeutic response. In a follow-up of 33 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 actual median DFS was 17 months. Patients with white blood cell (WBC) count below 10 × 109/L at relapse had better survival than those with WBC count over 10 × 109/L (P = .038). The duration of As2O3-induced CR was related to postremission therapy, because there was only 2 of 11 relapses in patients treated with As2O3 combined with chemotherapy, compared with 12 of 18 relapses with As2O3 alone (P = .01). Reverse transcription polymerase chain reaction (RT-PCR) analysis in both newly diagnosed and relapsed groups showed long-term use of As2O3 could lead to a molecular remission in some patients. We thus recommend that ATRA be used as first choice for remission induction in newly diagnosed APL cases, whereas As2O3 can be either used as a rescue for relapsed cases or included into multidrug consolidation/maintenance clinical trials.

Long‐term outcome of relapsed acute promyelocytic leukemia treated with oral arsenic trioxide‐based reinduction and maintenance regimens: A 15‐year prospective study

“…1 Previous studies indicated that patients in CR2 had poor long-term relapse-free survival rates of only 22% to 37%. 6,20,21 HSCT is conventionally regarded as a consolidation strategy.…”

“…[2][3][4][5] Arsenic trioxide (As 2 O 3 ) delivered intravenously (intravenous As 2 O 3 ) is highly efficacious for APL in first relapse (R1), inducing second complete remission (CR2) in >90% of patients. 6,7 Similar to other acute myeloid leukemias, consolidation of CR2 with autologous or allogeneic hematopoietic stem cell transplantation (HSCT) is then recommended. 1 However, prospective data validating HSCT or other approaches as the optimal postremission therapy for APL in CR2 are not available.…”

Acute promyelocytic leukemia: A population‐based study on incidence and survival in the United States, 1975‐2008

“…36,37 ATO alone or in combination with ATRA is an excellent option for older patients, who often cannot tolerate anthracycline-based therapy. [31][32][33][38][39][40] It will also be interesting to see the impact of ATO on the survival of this particular population in the future.…”

Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single‐arm study

“…Arsenic trioxide (ATO) is an antineoplastic chemotherapeutic agent approved for the treatment of relapsed or refractory acute promyelocytic leukaemia (APL; Niu et al, 1999;Soignet et al, 2001). The use of ATO to treat MM is supported by preclinical studies in which this agent has been shown to inhibit growth, reduce viability and induce apoptosis in several myeloma cell lines at concentrations that can be safely achieved in patients (Park et al, 2000;Perkins et al, 2000;Hideshima et al, 2002;Campbell et al, 2004a).…”