General AML

The prognostic impact of consolidation history in MRD negative AML patients undergoing allogenic HCT

A history of prior consolidation before Allogenic Hematopoietic Cell Transplantation (allo-HCT) is associated with favorable outcomes in Minimal Residual Disease (MRD) negative Acute Myeloid Leukemia (AML) patients in First Complete Remission (CR1) according to a study published ahead of print in the American Journal of Hematology on 24th June 2017.

In AML, achieving MRD negativity in CR1 before allo-HCT is associated with reduced relapse risk. However, approximately 30% of MRD negative AML patients who undergo allo-HCT relapse, thus suggesting that other prognostic factors may be involved. Armin Rashidi and colleagues from the University of Minnesota, Minneapolis, retrospectively studied whether a history of prior consolidation has any prognostic impact in MRD-negative AML patients undergoing allo-HCT in CR1.

In total, 126 AML patients (median age = 60 years) who underwent allo-HCT in CR1 with (n = 62) or without (n = 64) prior consolidation between January 2003 to April 2016 at the University of Minnesota were included in this study.

The key results of the study were:
  • 5-year Overall Survival (OS) in MRD negative patients who underwent allo-HCT with or without prior consolidation; 61% vs 38%, P = 0.048
  • 5-year Relapse Free Survival (RFS) in MRD negative patients who underwent allo-HCT with or without prior consolidation; 53% vs 32%, P = 0.030
  • 5-year incidence of relapse in MRD negative patients who underwent allo-HCT with or without prior consolidation; 29% vs 44%, P = 0.053

In summation, among MRD-negative patients undergoing allo-HCT, prior history of consolidation is associated with a favorable OS, RFS and relapse risk.

The authors concluded by suggesting that their study “can improve prognostication accuracy in patients referred for HCT in MRD-negative state”. They further added the results of their study would need to be validated in a prospective clinical study and highlighted that a multi-center study has been designed to validate the results.

Abstract

Background: Prognostic factors among acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in minimal residual disease (MRD)-negative first complete remission (CR1) are unknown. We retrospectively attempted to answer the following question: In AML patients undergoing allo-HCT in MRD-negative CR1, does a history of prior consolidation provide additional prognostic information? Methods: The inclusion criteria were: (i) Age > 18 years, (ii) AML in CR1 after 1-2 cycles of intensive induction chemotherapy, with or without consolidation, (iii) Allo-HCT between 1/2003 and 4/2016 at our institution, (iv) Available standard-sensitivity 4-color flow cytometry results from a bone marrow aspiration at diagnosis and after completion of all previous chemotherapy within one month prior to HCT, (v) Flow cytometry-based MRD-negative status at the time of HCT. Results: A history of prior consolidation was associated with favorable overall survival (Hazard Ratio [95% Confidence Interval]: 0.59 [0.35-0.99], P = 0.046), relapse-free survival (0.60 [0.37-0.96], P = 0.036), and relapse (0.50 [0.27-0.92], P = 0.025). Analysis of potential sources of bias was unrevealing. Conclusions: In AML patients undergoing allo-HCT in MRD-negative CR1 state, a history of prior consolidation was associated with favorable outcomes. If the path to pre-HCT MRD negativity includes consolidation, it may identify patients with improved prognosis following HCT in MRD-negative state. These results warrant validation in larger cohorts.

References
  1. Rashidi A. et al. History of consolidation is prognostic in AML patients undergoing allogeneic hematopoietic cell transplantation in minimal residual disease-negative first complete remission. Am J Hematol. 2017 Jun 24. DOI: 10.1002/ajh.24834. [Epub ahead of print].