Is It Time to Reconsider Allogeneic SCT in NPM1-Mutant AML?

Allogeneic stem cell transplantation (SCT) significantly improved rates of relapse-free survival (RFS), but not overall survival (OS) in patients with acute myeloid leukemia (AML) who also harbored a mutated nucleophosmin-1 gene (NPM1), according to results recently reported in the Journal of Clinical Oncology.

NPM1 mutations, which are present in a large percentage of patients with AML who have a normal karyotype, are considered a favorable prognostic marker and are associated with improved outcomes and remission rates. While patients with high-risk profiles are typically referred for transplantation, patients with more favorable risk profiles, such as those with NPM1-mutant AML, are more likely to receive chemotherapy alone. So, should NPM1-mutant AML patients be referred for allogeneic SCT or chemotherapy alone as post-remission therapy?

In this donor versus no-donor analysis, lead author Christopher Röllig, MD, from University Hospital Dresden in Germany, and colleagues compared the clinical courses of patients with NPM1-mutant AML who were eligible for allogeneic SCT to assess its predictive value.

Results from the analysis were also presented by Dr. Röllig at ASH’s 56th Annual Meeting late last year.

Of 1,179 patients with AML (age range, 18–60 years) enrolled in the Study Alliance Leukemia AML 2003 trial, investigators retrospectively identified 375 NPM1-mutant patients (31.8%) with an intermediate-risk karyotype – 304 were eligible for the analysis.

According to the trial protocol, patients received an allogeneic SCT if an HLA-identical sibling donor was available. If no donor was available, patients received consolidation or autologous SCT.

Seventy-seven of these patients had an HLA-identical sibling donor: 55 underwent transplantation at the time of first complete remission, and seven underwent transplantation at the time of relapse. The remaining 227 patients without a sibling donor received chemotherapy alone.

Over a median follow-up of 52 months, a large proportion of patients experienced complete remission. Significantly more patients in the donor cohort achieved three-year RFS than those in the no-donor cohort (p=0.005); however, availability of an HLA-matched sibling donor did not significantly impact rates of three-year overall survival (TABLE).

Investigators further evaluated data from 148 patients with normal karyotype and no FLT3 internal tandem duplication (43 of whom had a sibling donor):

  • 3-year RFS rates were 83% and 53% in the donor and no-donor groups, respectively (p=0.004)
  • 3-year OS rates were 81% and 75%, respectively (p=0.300)

Notably, median RFS was 27 months among patients without a donor and was not yet reached among patients with a donor. Median OS had not been reached in either cohort at the time of the analysis.

The lack of OS benefit with allogeneic SCT in these patients may be due to the favorable outcomes after salvage treatment, researchers noted. “NPM1-mutant patients who experienced relapse responded well to salvage treatment,” Dr. Röllig said, “allowing the achievement of a second remission in 65 percent of patients by re-induction and subsequent salvage transplantation from an allogeneic donor in 47 percent of patients.”

“Our study suggests that allogeneic SCT seems to represent a valuable consolidation choice for patients with NPM1-mutant AML in first complete remission if a sibling donor is available, especially in young patients with a relatively low risk of non-relapse mortality,” Dr. Röllig and colleagues concluded.


Röllig C, Bornhäuser M, Kramer M, et al. 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. J Clin Oncol. 2014 December 29. [Epub ahead of print]

Donors (N=77) No-donors (N=277)
Complete remission 95% 89%
3-Year relapse-free survival 71% 47%
3-Year overall survival 70% 60%