Allogeneic Stem-Cell Transplantation in Patients With NPM1-Mutated Acute Myeloid Leukemia: Results From a Prospective Donor Versus No-Donor Analysis of Patients After Upfront HLA Typing Within the SAL-AML 2003 Trial

Abstract

Purpose: The presence of a mutated nucleophosmin-1 gene (NPM1_mut) in acute myeloid leukemia (AML) is associated with a favorable prognosis. To assess the predictive value with regard to allogeneic stem-cell transplantation (SCT), we compared the clinical course of patients with NPM1_mut AML eligible for allogeneic SCT in a donor versus no-donor analysis. Patients and Methods: Of 1,179 patients with AML (age 18 to 60 years) treated in the Study Alliance Leukemia AML 2003 trial, we identified all NPM1_mut patients with an intermediate-risk karyotype. According to the trial protocol, patients were intended to receive an allogeneic SCT if an HLA-identical sibling donor was available. Patients with no available donor received consolidation or autologous SCT. We compared relapse-free survival (RFS) and overall survival (OS) depending on the availability of a suitable donor. Results: Of 304 eligible patients, 77 patients had a sibling donor and 227 had no available matched family donor. The 3-year RFS rates in the donor and no-donor groups were 71% and 47%, respectively (P = .005); OS rates were 70% and 60%, respectively (P = .114). In patients with normal karyotype and no FLT3 internal tandem duplication (n = 148), the 3-year RFS rates in the donor and no-donor groups were 83% and 53%, respectively (P = .004); and the 3-year OS rates were 81% and 75%, respectively (P = .300). Conclusion: Allogeneic SCT led to a significantly prolonged RFS in patients with NPM1_mut AML. The absence of a statistically significant difference in OS is most likely a result of the fact that NPM1_mut patients who experienced relapse responded well to salvage treatment. Allogeneic SCT in first remission has potent antileukemic efficacy and is a valuable treatment option in patients with NPM1_mut AML with a sibling donor.