General AML

MRD status and cytogenetic classification predicts outcome of autologous and allogenic stem cell transplantation in AML patients in first remission: A Chinese study

Stem Cell Transplantation (SCT) is one of the most effective therapies in Acute Myeloid Leukemia (AML) patients in First Remission (CR1). Allogenic SCT (allo-SCT) reduces disease relapse but it is associated with high Non Relapse Mortality (NRM). Alternatively, Autologous SCT (auto-SCT) is associated with low NRM but high disease relapse. The decision to either use allo-SCT or auto-SCT in AML patients in CR1 remains debatable1, hence the rationale for this study. Cytogenetic classification and Minimal Residual Disease (MRD) are powerful predictors for prognosis for AML patients. There is a paucity of studies exploring the combination of cytogenetic classification with MRD monitoring in the prediction of prognosis and decision making between auto-SCT and allo-SCT.

Jianfeng Yao, from the Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), and colleagues published an article in Leukemia Research which retrospectively studied the clinical significance of the combination of MRD detection and cytogenetic classification in predicting prognosis in primary AML patients in CR1 who received either allo-SCT or auto-SCT from a single transplant centre2.

In this study, 172 AML patients were enrolled. The patients either had auto-SCT (auto group, n = 46, median age = 32.5 years) or allo- SCT (allo group, n = 126, median age = 38.0 years).

The key results of the study were:
  • 3-year Overall Survival (OS) in the allo group and auto group; 74.6% vs 73.6%, P = 0.616
  • 3-year Disease Free Survival (DFS) in the allo group and auto group; 73.6% vs 69.1%, P = 0.559
  • After transplant, 3-year leukemia relapse in allo group and auto group; 14.1% (16/126) vs 26.6% (11/46); P = 0.083
  • After one course of consolidation, cytogenetic classification and MRD were independent risk factors for OS; HR = 1.758, P = 0.012, and HR = 2.772, P = 0.006, respectively
  • After one course of consolidation, cytogenetic classification and MRD were independent risk factors for DFS; HR = 1.800, P = 0.007, and HR = 2.042, P = 0.049, respectively
  • DFS after allo-SCT and auto-SCT in patients with favorable or intermediate risk and MRD positive were 57.8% and 14.3%, respectively; P = 0.001
  • Leukemia relapse after allo-SCT and auto-SCT in patients with favorable or intermediate risk and MRD positive were 23.3% and 85.7%, respectively; P = 0.001
  • DFS after allo-SCT and auto-SCT in patients with favorable or intermediate risk and MRD negative were 84.4% and 93.5%, respectively; P = 0.270
  • Leukemia relapse after allo-SCT and auto-SCT in patients with favorable or intermediate risk and MRD negative were 8% and 0%, respectively; P = 0.110

In summation, MRD and cytogenetic classification after one course of consolidation can independently predict prognosis of AML patients after transplant. Additionally, auto-SCT and allo-SCT offered similar survival outcomes in AML patients with favorable and intermediate risk and MRD negative after one course of consolidation. However, AML patients with favorable or intermediate risk and are MRD positive after one course of consolidation had inferior survival and higher risk of relapse if they were transplanted with auto-SCT compared to allo-SCT.

The authors highlighted that the small size was a limitation to their study establish accurate criteria and they recommend that prospective studies should be carried out to confirm their data. The authors concluded by stating that combining cytogenetic classification and MRD status correlates with the outcome of auto- SCT versus allo-SCT and may offer a better choice between the SCT types for adults with AML in CR1.

Abstract

Both autologous and allogeneic stem cell transplantation (auto- and allo-SCT) are treatment choice for adults with acute myeloid leukemia (AML) after complete remission (CR). However, the decision-making remains controversial in some situations. To figure out the treatment choice, we retrospectively investigated 172 consecutive patients with primary AML who received auto- (n=46) or allo-SCT (n=126) from a single transplant center. Auto- and allo-SCT group demonstrated comparable overall survival (OS) and disease-free survival (DFS) (P=0.616, P=0.559, respectively). Cytogenetic classification and minimal residual disease (MRD) after one course of consolidation were identified as independent risk factors for DFS (hazard ratio (HR), 1.800; 95% CI, 1.172-2.763; P=0.007; HR, 2.042; 95%CI, 1.003-4.154; P=0.049; respectively). We subsequently found that auto- and allo-SCT offered comparable DFS to patients with favorable or intermediate risk and were tested MRDneg after one course of consolidation (P=0.270) otherwise auto-SCT were inferior due to increased risk of leukemia relapse. Our study indicated that the combination of cytogenetic classification and MRD monitoring correlated with outcome of auto- versus allo-SCT and might help the choice between the two types of SCT for adults with primary AML, which is of significance for patients with expected intermediate prognosis in the current scenario.

References
  1. Saraceni F. et al. Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT. J Hematol Oncol. 2016 Sep 2; 9(1):79. DOI: 1186/s13045-016-0314-x.
  2. Yao J. et al. Combination of cytogenetic classification and MRD status correlates with outcome of autologous versus allogeneic stem cell transplantation in adults with primary acute myeloid leukemia in first remission. Leuk Res. 2017 Jan 23; 55:97–104. DOI: 1016/j.leukres.2017.01.026. [Epub ahead of print].