Allogeneic hematopoietic cell transplantation in intermediate risk acute myeloid leukemia negative for FLT3 -ITD, NPM1- or biallelic CEBPA mutations

Abstract

Background

The value of allogeneic hematopoietic cell transplantation (alloHCT) as postremission treatment is not well defined for patients with intermediate-risk acute myeloid leukemia (AML) without FLT3-ITD, biallelic CEBPA-, or NPM1 mutations (here referred to as NPM1^mut-neg/CEBPA^dm-neg/FLT3-ITD^neg AML) in first complete remission (CR1).

Patients and methods

We addressed this question using data from two prospective randomized controlled trials on intensive induction- and risk-stratified postremission therapy. The NPM1^mut-neg/CEBPA^dm-neg/FLT3-ITD^neg AML subgroup comprised 497 patients, aged 18–60 years.

Results

In donor versus no-donor analyses, patients with a matched related donor had a longer relapse-free survival (HR 0.5; 95% CI 0.3–0.9, P = 0.02) and a trend toward better overall survival (HR 0.6, 95% CI 0.3–1.1, P = 0.08) compared with patients who received postremission chemotherapy. Notably, only 58% of patients in the donor group were transplanted in CR1. We therefore complemented the donor versus no-donor analysis with multivariable Cox regression analyses, where alloHCT was tested as a time-dependent covariate: overall survival (HR 0.58, 95% CI 0.37–0.9, P = 0.02) and relapse-free survival (HR 0.51, 95% CI 0.34–0.76; P = 0.001) for patients who received alloHCT compared with chemotherapy in CR1 were significantly longer.

Conclusion

Outside clinical trials, alloHCT should be the preferred postremission treatment of patients with intermediate risk NPM1^mut-neg/CEBPA^dm-neg/FLT3-ITD^neg AML in CR1.

Cinicaltrials.gov identifier

NCT00180115, NCT00180102