Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease

Christopher S. Hourigan, Laura W. Dillon, Gege Gui, Brent R. Logan, Mingwei Fei, Jack Ghannam, Yuesheng Li, Abel Licon, Edwin P. Alyea, Asad Bashey, H. Joachim Deeg, Steven M. Devine, Hugo F. Fernandez, Sergio Giralt, Mehdi Hamadani, Alan Howard, Richard T. Maziarz, David L. Porter, Bart L. Scott, Erica D. WarlickMarcelo C. Pasquini, Mitchell E. Horwitz

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

PURPOSE Patients with acute myeloid leukemia (AML) in remission remain at risk for relapse even after allogeneic hematopoietic cell transplantation (alloHCT). AML measurable residual disease (MRD) status before alloHCT has been shown to be prognostic. Whether modulation of the intensity of the alloHCT conditioning regimen in patients with AML who test positive for MRD can prevent relapse and improve survival is unknown. METHODS Ultra-deep, error-corrected sequencing for 13 commonly mutated genes in AML was performed on preconditioning blood from patients treated in a phase III clinical trial that randomly assigned adult patients with myeloid malignancy in morphologic complete remission to myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC). RESULTS No mutations were detected in 32% of MAC and 37% of RIC recipients; these groups had similar survival (3-year overall survival [OS], 56% v 63%; P = .96). In patients with a detectable mutation (next-generation sequencing [NGS] positive), relapse (3-year cumulative incidence, 19% v 67%; P, .001) and survival (3-year OS, 61% v 43%; P = .02) was significantly different between the MAC and RIC arms, respectively. In multivariable analysis for NGS-positive patients, adjusting for disease risk and donor group, RIC was significantly associated with increased relapse (hazard ratio [HR], 6.38; 95% CI, 3.37 to 12.10; P, .001), decreased relapse-free survival (HR, 2.94; 95% CI, 1.84 to 4.69; P, .001), and decreased OS (HR, 1.97; 95% CI, 1.17 to 3.30; P = .01) compared with MAC. Models of AML MRD also showed benefit for MAC over RIC for those who tested positive. CONCLUSION This study provides evidence that MAC rather than RIC in patients with AML with genomic evidence of MRD before alloHCT can result in improved survival.

Original languageEnglish (US)
Pages (from-to)1273-1283
Number of pages11
JournalJournal of Clinical Oncology
Volume38
Issue number12
DOIs
StatePublished - Apr 20 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hourigan, C. S., Dillon, L. W., Gui, G., Logan, B. R., Fei, M., Ghannam, J., Li, Y., Licon, A., Alyea, E. P., Bashey, A., Deeg, H. J., Devine, S. M., Fernandez, H. F., Giralt, S., Hamadani, M., Howard, A., Maziarz, R. T., Porter, D. L., Scott, B. L., ... Horwitz, M. E. (2020). Impact of conditioning intensity of allogeneic transplantation for acute myeloid leukemia with genomic evidence of residual disease. Journal of Clinical Oncology, 38(12), 1273-1283. https://doi.org/10.1200/JCO.19.03011