The use of flow cytometry (FCM) for measurable residual disease (MRD) testing in T-cell acute lymphoblastic leukemia (T-ALL) was found to be an effective technique for estimating relapse risk, according to a report in the journal Leukemia.
In most patients with T-ALL, relapse risk can be estimated through MRD analysis based on polymerase chain reaction (PCR). However, an appropriate marker may not be available for some patients for PCR analysis.
Throughout this study of 274 patients with T-ALL treated with the NOPHO ALL2008 protocol in Europe, concurrent PCR-based MRD (PCR-MRD) and FCM-based MRD (FCM-MRD) analyses were performed for risk assessments. Bone marrow aspirates were obtained for MRD analysis on days 0, 15, and 29 following the start of induction therapy. Additional samples were taken from patients showing intermediate or higher risk based on earlier samplings, with consolidation therapies adjusted accordingly.
More patients (93%) had useful markers for FCM-MRD analysis compared with patients with useful markers for PCR-MRD analysis (84%), with only 0.7% of patients having no suitable marker for either method.
PCR-MRD and FCM-MRD results were highly correlated for double-positive samples, with a Spearman correlation coefficient (r) of 0.85 (P <.0001) on day 15. For day 29 results, r was 0.73 (P <.0001).
The event-free survival rate at 5 years was 74.8% (95% CI, 70%-80%) overall, with a relapse risk of 14.1% (95% CI, 10%-19%). Relapse occurred during follow-up in 35 patients.
The hazard ratio (HR) for relapse, adjusted for both age and white blood cell count, was 3.55 (95% CI, 1.4-9.0; P =.008) for patients with an FCM-MRD result of at least 10-3 on day 29 compared with patients with FCM-MRD below 10-3. The comparable HR with a PCR-MRD result of at least 10-3 was 5.6 (95% CI, 2.0-16; P =.001).
Area-under-the-curve analyses gave values of 0.75 for PCR-MRD and 0.67 for FCM-MRD for predicting relapse risk (for 14 relapses in 149 patients; P =.37).
For patients showing day 15 FCM-MRD below 10-4, the incidence of relapse was 2.3% (95% CI, 0%-6.8%).
Overall, FCM-MRD and PCR-MRD results were consistent enough with each other that the authors suggested FCM-MRD may be suitable for risk assessment in T-ALL when PCR-MRD is not an option.
- Modvig S, Madsen HO, Siitonen SM, et al. Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia [published online December 14, 2018]. Leukemia. doi:10.1038/s41375-018-0307-6