Improved long‐term survival in all Sanz risk patients of newly diagnosed acute promyelocytic leukemia treated with a combination of retinoic acid and arsenic trioxide‐based front‐line therapy

Abstract

Limited data was available for long-term follow-up in newly diagnosed acute promyelocytic leukemia (APL) patients treated with all-trans-retinoic acid (ATRA) plus intravenously arsenic trioxide (ATO)-based front-line therapy. The aim of this work was to retrospectively analyze the long-term survival rate and frequency of therapy-related myeloid neoplasia (t-MN) occurring in a large cohort of APL patients. A total of 760 newly diagnosed patients with APL between January 1999 and May 2016 were evaluated. The early death rate was 9.2% (70/760). Of the remaining 690 patients with complete remission, patients were grouped according to front-line regimens: ATRA plus ATO with or without chemotherapy (ATO group) and ATRA with chemotherapy (non-ATO group). The median duration of follow-up was 7.5 years (1.0-18.3 years). ATO group showed significant superior 10-year estimated relapse-free survival (RFS) up to 90.3% comparing with 65.5% in the non-ATO group (P < 0.0001). In addition, the 10-year estimated overall survival (OS) was 93.9% for patients in the ATO group and 89.1% for those in the non-ATO group (P = 0.03). In the subgroup analysis, the RFS rate was also higher in ATO group comparing with non-ATO group in both low-to-intermediate-risk (94.2% vs 64.6%, P < 0.0001) and high-risk subgroup (89.6% vs 74.7%, P = 0.04). Notably, the 3-year RFS and OS rates in the chemotherapy-free subgroup of the low-to-intermediate-risk patients (n = 88) were 100% and 100%, respectively. In the entire cohort, a total of 10 patients developed secondary malignant neoplasms, including 7 patients with therapy-related myeloid neoplasms (t-MN). The estimated 5-year cumulative incidence risk of t-MN in the ATO and non-ATO groups was 1.0% and 0.4%, respectively (P = 0.34). Thus, our data revealed that the long-term outcome of patients treated with ATRA plus ATO-based regimens was associated with continuing high efficacy in all Sanz risk patients with newly diagnosed APL.

Metal Drugs and the Anticancer Immune Response

“…Besides the prevalent and severe complication caused by ATO and ATRA, termed differentiation syndrome (believed to be mediated by the release of pro-inflammatory cytokines from malignant promyelocytes), the development of secondary hematological malignancies cannot be excluded. A recent study on long-term survival of APL patients treated with ATRA and ATO revealed an estimated 5-year cumulative incidence risk of 1.0% to develop therapy-related myeloid neoplasms . In contrast, an independent report demonstrated no increased risk of secondary cancers following ATRA- and ATO-based therapy of APL …”

“…A recent study on long-term survival of APL patients treated with ATRA and ATO revealed an estimated 5-year cumulative incidence risk of 1.0% to develop therapy-related myeloid neoplasms. 1219 In contrast, an independent report demonstrated no increased risk of secondary cancers following ATRA-and ATO-based therapy of APL. 1220 In addition to the clinically approved Pt and As compounds, the application of several radioactive metal isotopes is also implicated in the occurrence of secondary malignancies.…”

Predictors of early death and clinical features in newly diagnosed patients with low-intermediate risk acute promyelocytic leukemia

“…Acute promyelocytic leukaemia (APL) has become a highly curable hematologic neoplastic disease with a 10-year overall survival (OS) rate of 93.9% ( 1 ), due to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). However, a population-based epidemiological study showed that the early death rate within 30 days can still be as high as 29% ( 2 ).…”

Effects of peripheral blood leukocyte count and tumor necrosis factor-alpha on early death in acute promyelocytic leukemia

“…Acute promyelocytic leukemia (APL) has become a highly curable hematologic neoplastic disease with a 10-year overall survival (OS) rate of 93.9% [ 1 ] due to the use of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). With increasingly effective treatments, early mortality can still be as high as 32.6–34.6% [ 2 – 4 ].…”