Flow Cytometric Minimal Residual Disease Highly Prognostic in AML Patients Aged Under 60
In a study reported in Journal of Clinical Oncology, Monique Terwijn, PhD, of the VU University Medical Centre in Amsterdam, and colleagues assessed the prognostic performance of flow cytometric minimal residual disease detection in acute myeloid leukemia (AML) patients aged < 60 years. They found that minimal residual disease status was a strong prognostic factor for relapse and that minimal residual disease–positive patients with late complete remission are at risk for poor outcome.
Study Details
The study involved adults with AML aged < 60 years enrolled in the Dutch-Belgian Hemato-Oncology Cooperative Group/Swiss Group for Clinical Cancer Research Acute Myeloid Leukemia 42A study. Flow cytometric minimal residual disease was evaluated in bone marrow samples in patients achieving complete remission after induction cycle 1 (n = 164), induction cycle 2 (n = 183), and consolidation therapy (n = 124).
Minimal Residual Disease Status Predictive of Relapse and Survival
With a cutpoint of 0.1% distinguishing minimal residual disease–negative patients (minimal residual disease ≤ 0.1%) from minimal residual disease–positive patients, the risk of relapse was significantly higher in minimal residual disease–positive patients after cycle 1 (P = .005), cycle 2 (P < .001), and consolidation (P < .001). Both overall survival (P = .03, < .001, and = .008) and relapse-free survival (P = .008, = .001, and < .001) were significantly poorer after the three cycles of treatment, respectively. In the entire patient group and in the subgroup with intermediate-risk cytogenetics, minimal residual disease was an independent prognostic factor for relapse.
Hazard ratios (HRs) for relapse in minimal residual disease–positive vs -negative patients after cycle 2 (adjusted for complete remission, AML risk category, white blood cell count, consolidation treatment, age, and granulocyte colony-stimulating factor use) were 13.0 (95% confidence interval [CI] = 5.3–32.1) during 0 to 6 months, 4.7 (95% CI = 2.1–10.5) during 7 to 12 months, and 0.7 (95% CI = 0.2–2.4) after 12 months. The difference among the three hazard ratios was highly significant (P < .001), indicating that minimal residual disease status is a strong prognostic indicator for risk of relapse only in the first year.
Poor Outcome With Minimal Residual Disease Positivity and Late Complete Remission
After cycle 2—ie, when decisions about consolidation are made—minimal residual disease–positive patients had a significantly greater risk of relapse in analysis by good cytogenetic risk (P = .05), intermediate risk (P < .001), and poor risk (P = .007). The hazard ratio for minimal residual disease–positive patients with late complete remission was much higher (6.76) than that for patients with complete remission after cycle 1 (1.42, P = .006 for interaction), indicating that late complete remission together with minimal residual disease positivity after cycle 2 portends an extremely poor outcome. On multivariate analysis after cycle 2, minimal residual disease–positive patients had a higher risk of relapse after adjustment for consolidation treatment time-dependent covariate risk score and early or later complete remission (HR = 2.60, P = .001).
The investigators concluded, “In future treatment studies, risk stratification should be based not only on risk estimation assessed at diagnosis but also on [minimal residual disease] as a therapy-dependent prognostic factor.”
Gerrit J. Schuurhuis, PhD, of VU University Medical Center in Amsterdam, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported in part by the Dutch Cancer Society.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
