Potent Graft-Versus-Leukemia Effect After Reduced-Intensity Allogeneic SCT for Intermediate-Risk AML With FLT3-ITD or Wild-Type NPM1 and CEBPA Without FLT3-ITD

Biol Blood Marrow Transplant. 2012 Dec;18(12):1845-50. doi: 10.1016/j.bbmt.2012.06.012. Epub 2012 Jul 2.

Abstract

To investigate the role of reduced-intensity allogeneic (RIC-allo) stem cell transplant (SCT) as postremission therapy in adult intermediate-risk patients with acute myelogenous leukemia (AML) with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD, we conducted a single-center retrospective study between January 2001 and December 2010. Sixty-six patients were included: 37 treated with RIC-alloSCT and 29 with nonallogeneic SCT therapies. Both groups were comparable concerning age, WBC count at diagnosis, gender, karyotype, genotype, and number of courses of chemotherapy to reach complete remission (CR1). Median follow-up after CR1 was 37 months (range, 11-112 months) and 48 months (range, 9-83 months) in the allo and no-allo groups, respectively. In the allo versus no-allo groups, the 3-year cumulative incidence of relapse (CIR) rates were 25% ± 8% versus 61% ± 9%; P = .005. The 3-year nonrelapse mortality (NRM), overall survival (OS), and relapse-free survival (RFS) were 22% ± 7% versus 4% ± 4% (P = .005), 52% ± 9% versus 44% ± 10% (P = .75), and 53% ± 9% versus 35% ± 9% (P = .28), respectively. Multivariate analysis indicated that CIR was reduced by allo (hazard ratio [HR], 0.32; P = .01). A landmark analysis performed at day 185 after CR1 confirmed a lower CIR after allo. RIC-allo reduces the risk of relapse, suggesting a potent graft-versus-leukemia (GVL) effect in these patients at a high risk of relapse.

MeSH terms

  • Adult
  • Aged
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Disease-Free Survival
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Leukemia Effect / physiology*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / surgery*
  • Male
  • Middle Aged
  • Mutation
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Retrospective Studies
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • Survival Rate
  • Tandem Repeat Sequences
  • Transplantation, Homologous
  • Young Adult
  • fms-Like Tyrosine Kinase 3 / genetics*
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • Nuclear Proteins
  • nucleophosmin
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3