Allogeneic hematopoietic cell transplantation in intermediate risk acute myeloid leukemia negative for FLT3-ITD, NPM1- or biallelic CEBPA mutations.
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 NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg 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 NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg 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 NPM1mut-neg/CEBPAdm-neg/FLT3-ITDneg AML in CR1.


Cinicaltrials.gov identifier
NCT00180115, NCT00180102.
['Heidrich|K|K|', 'Thiede|C|C|', 'Schäfer-Eckart|K|K|', 'Schmitz|N|N|', 'Aulitzky|W E|WE|', 'Krämer|A|A|', 'Rösler|W|W|', 'Hänel|M|M|', 'Einsele|H|H|', 'Baldus|C D|CD|', 'Trappe|R U|RU|', 'Stölzel|F|F|', 'Middeke|J M|JM|', 'Röllig|C|C|', 'Taube|F|F|', 'Kramer|M|M|', 'Serve|H|H|', 'Berdel|W E|WE|', 'Ehninger|G|G|', 'Bornhäuser|M|M|', 'Schetelig|J|J|', '|||']
D000293:Adolescent D000328:Adult D014408:Biomarkers, Tumor D022762:CCAAT-Enhancer-Binding Proteins D005260:Female D005500:Follow-Up Studies D018380:Hematopoietic Stem Cell Transplantation D006801:Humans D015470:Leukemia, Myeloid, Acute D008297:Male D008875:Middle Aged D009154:Mutation D009687:Nuclear Proteins D000090243:Nucleophosmin D011379:Prognosis D011446:Prospective Studies D012074:Remission Induction D015996:Survival Rate D014184:Transplantation, Homologous D055815:Young Adult D051941:fms-Like Tyrosine Kinase 3
acute myeloid leukemia FLT3-ITD CEBPA NPM1 postremission therapy hematopoietic stem cell transplantation