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 24^th 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.