Abstract
Background: Previous studies have suggested that NPM1 mutations may be a marker for response to all-trans retinoic acid (ATRA) given as an adjunct to intensive chemotherapy in older patients with acute myeloid leukemia (AML).Patients and Methods: We examined the impact of the addition of ATRA among patients with diploid cytogenetics treated on a randomized phase II study of fludarabine + cytarabine + idarubicine ± G-CSF ± ATRA with available data on their NPM1 mutation status. Between September 1995 and November 1997, 215 patients were enrolled in the study. Among them, 70 patients had diploid cytogenetic and are the subjects of this analysis.Results: The median age of the 70 patients was 66 years (range 23–87). Twenty (29%) of patients had NPM1 mutations. Among them 7 (35%) did and 13 (65%) did not receive ATRA in combination with chemotherapy. Complete remission (CR) was achieved in 71% of patients treated with ATRA as compared to 69% without ATRA (P = 0.62). With median follow-up of 12.5 years, the overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were similar among patients who received ATRA compared to no ATRA regardless of NPM1 mutation status.Conclusion: The addition of ATRA to intensive chemotherapy did not affect the overall outcome of patients with AML regardless of NPM1 mutation status.
Highlights
Complete remission (CR) was achieved in 71% of patients treated with all-trans retinoic acid (ATRA) as compared to 69% without ATRA (P = 0.62)
With median follow-up of 12.5 years, the overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were similar among patients who received ATRA compared to no ATRA regardless of NPM1 mutation status
The addition of ATRA to intensive chemotherapy did not affect the overall outcome of patients with acute myeloid leukemia (AML) regardless of NPM1 mutation status
Summary
The addition of all-trans retinoic acid (ATRA) to chemotherapy has changed the natural history of acute promyelocytic leukemia (APL) by inducing terminal differentiation of the promyelocyte into mature cells [1, 2]. Preclinical data suggests that ATRA may sensitize non-APL leukemic blasts to cytarabine and anthracyclines by downregulating bcl-2 and related proteins that inhibit apoptosis [3,4,5,6]. These observations provided a rationale for several clinical trials to evaluate the impact of adding ATRA to conventional chemotherapy in non-APL patients; the reports of these trials have been conflicting. Previous studies have suggested that NPM1 mutations may be a marker for response to all-trans retinoic acid (ATRA) given as an adjunct to intensive chemotherapy in older patients with acute myeloid leukemia (AML)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have