Salvage Therapy with Chemotherapy- or Arsenic Trioxide-Based Regimens for Acute Promyelocytic Leukemia in First Relapse.

Arsenic trioxide (ATO) is currently regarded as the best treatment option in relapsed acute promyelocytic leukemia (APL). The efficacy and safety of salvage therapy using an ATO-based approach compared with chemotherapy-based regimens is not well established. We analyze the clinical outcome of 110 APL patients relapsing after front-line therapy with ATRA and anthracycline, who received second-line therapy with chemotherapy- or ATO-based regimens.

From June 1997 to May 2009, 110 patients (69 M/41 F; median age: 40 years, 2-81) relapsed after front-line therapy with PETHEMA trials (LPA96, n=30, LPA99, n=60; and LPA2005, n=20). Patients presented with either molecular relapse (n=37) or hematological relapse (n=73, 14 of them involving central nervous system). Sixty-seven patients (61%) followed salvage therapy with chemotherapy-based regimens. Therapy consisted of induction with mitoxantrone plus cytarabine plus ATRA (n=46), EMA (n=7), or other chemotherapy regimens (n=14). Thirty-four patients (51%) received one consolidation cycle followed by stem-cell transplantation (SCT) (autologous, 20; allogeneic, 14). Patients not eligible for SCT received consolidation therapy with or without maintenance therapy. From October 2003, 43 patients (49%) received salvage therapy with ATO-based regimens, comprising induction with ATO (0.15 mg/kg intravenously until CR) followed by one consolidation cycle with ATO plus ATRA. Twenty-three patients (53%) received intensification therapy with SCT (autologous, 19; allogeneic, 4). Patients not eligible for SCT received maintenance therapy with ATO plus ATRA with or without Mylotarg or other chemotherapy.

Baseline characteristics, including age at relapse, were similar in both cohorts of patients, but patients treated with ATO-based regimens were more frequently late relapses (>18 months after initial APL diagnosis) (67% vs. 40%, P=0.005). The median follow-up in the chemotherapy-based group was 62 months (range, 6-134), and 18 months (range, 2-53) in the ATO-based group. CR rates were 84% in the chemotherapy-based group (8 deaths and 3 resistances) and 88% in the ATO-based group (3 deaths and 2 resistances) (P=0.48). Molecular remission was achieved after consolidation in 79% and 91%, respectively (P=0.13). Twenty-two patients of the chemotherapy-based group that achieved CR were not transplanted because of ineligibility for SCT (n=4), early relapse before planned SCT (n=7), mobilization failure (n=4), clinical decision/toxicity (n=6), and short follow-up (n=1). Reasons for not SCT in the ATO-based group were ineligibility for SCT (n=6), early relapse before planned SCT (n=5), and short follow-up (n=4). The 2-year overall survival (OS), disease-free (DFS), and relapse-free survival (RFS) in the chemotherapy-based group and in the ATO-based group were 44% vs. 63% (P=0.05), 34% vs. 33% (P=0.51), and 37% vs. 34% (P=0.61), respectively. For patients not receiving SCT, the 2-year OS, DFS, and RFS in the chemotherapy-based group and in the ATO-based group were 38% vs. 26% (P=0.98), 34% vs. 23% (P=0.57), and 37% vs. 23% (P=0.46), respectively. For patients receiving autologous SCT, the 2-year OS, DFS, and RFS in the chemotherapy-based group and in the ATO-based group were 60% vs. 87% (P=0.03), 40% vs. 38% (P=0.38), and 42% vs. 41% (P=0.37), respectively. For patients receiving allogeneic SCT, the 2-year OS, DFS, and RFS in the chemotherapy-based group and in the ATO-based group were 56% vs. 100% (P=0.15), 26% vs. 37% (P=0.46), and 28% vs. 37% (P=0.53), respectively.

this study performed in a large series of APL patients relapsing after upfront therapy with ATRA and anthracycline shows high rates of CR either with ATO (88%) or chemotherapy regimens (84%). The 2-year DFS and RFS were similar in patients who received second-line therapy with chemotherapy- or ATO-based regimens. However, an apparent benefit in terms of OS was observed in the ATO-based group (P=0.05), suggesting a potential role in minimizing toxicity after administering ATO as salvage therapy.

No relevant conflicts of interest to declare.