General AML,   FLT3,  Cohesin

Survival and relapse risk in AML patients with FLT3 mutations undergoing SCT

FMS-Like Tyrosine Kinase 3 (FLT3) mutation is associated with poor survival outcomes and high relapse rates in Acute Myeloid Leukemia (AML) patients. However, the impact of Minimal Residual Disease (MRD) detected by Polymerase Chain Reaction (PCR) before allogeneic Stem Cell Transplant (SCT) in AML patients with FLT3 mutations is not very clear.

Sameh Gaballa and colleagues from The University of Texas MD Anderson Cancer Center (MDACC) retrospectively studied the impact of disease status, mutated FLT3 detected by PCR, before transplant on relapse and survival of FLT3 mutated AML patients treated with SCT. The results of the study were published in the American Journal of Hematology.

Two-hundred AML patients (median age = 51 years) with FLT3 mutations who underwent SCT between January 2000–October 2014 at the MDACC were included in this study. At the time of transplant, patients were either in First Complete Remission (CR1, n = 99), Second Complete Remission (CR2, n = 20), High-risk Remission (CR-HR, n = 31), or had morphological Active Disease (AD, n = 50). Twenty-seven patients who were either in CR1, CR2, or CR-HR had detectable FLT3 MRD by PCR.

The key results of the study were:
  • 2-year cumulative incidence of relapse in patients in CR1/CR2 FLT3 MRD+, CR1/CR2 FLT3 MRD-, CR-HR FLT3 MRD+, CR-HR FLT3 MRD-, and with morphological AD; 39% vs 23% vs 72% vs 58% vs 85%
  • Detectable morphological AD and molecular detection of FLT3 MRD at the time of transplant were associated with higher risk of relapse
  • 2-year Overall Survival (OS) and Progression Free Survival (PFS) in all patients were 43% and 41%, respectively
  • In total, 110 patients died mostly due to leukemia relapse (n = 75)

In summary, disease status both morphologically and molecularly before transplant is an important predictor of disease relapse and survival post-transplant in patients with FLT3 mutated AML.

Abstract

In patients with AML with FMS-like tyrosine kinase 3 (FLT3) mutations, the significance of minimal residual disease (MRD) detected by PCR before allogeneic stem cell transplantation (SCT) on outcomes after transplant remains unclear. We identified 200 patients with FLT3-AML who underwent SCT at our institution. Disease status at transplant was: first or second complete remission (CR1/CR2, n = 119), high-risk CR (third or subsequent CR, marrow hypoplasia, or incomplete count recovery) (CR-HR, n = 31), and morphological evidence of active disease (AD, n = 50). The median follow-up was 27 months, and the 2-year overall and progression-free survival were 43% and 41%, respectively. Relapse was highest in the AD group (85%) and the CR-HR FLT3 MRD positive group (72%), followed by CR-HR FLT3 MRD negative (58%), CR1/CR2 FLT3 MRD positive (39%), and lowest in the CR1/CR2 FLT3 MRD negative group (23%). On multivariate analysis, independent factors influencing the risk of relapse were detectable morphological disease and FLT3 MRD by PCR pre-transplant. Factors that did not influence the relapse risk included: age, graft type, graft source, type of FLT3 mutation, or conditioning intensity. Morphologic and molecular remission status at the time of transplant were key predictors of disease relapse and survival in patients with FLT3-AML.

References
  1. Gaballa S.et al. Relapse risk and survival in patients with FLT3 mutated acute myeloid leukemia undergoing stem cell transplantation. Am J Hematol. 2017 Apr; 92(4): 331–337. DOI: 10.1002/ajh.24632