Sensitivity and Specificity of Chimerism Tests in Predicting Leukemia Relapse Using Increasing Mixed Chimerism

Area of Science:

• Hematology
• Oncology
• Transplant Medicine

Background:

• Stem cell transplantation is a curative option for hematologic malignancies.
• Monitoring chimerism post-transplant is crucial for detecting relapse.
• Increasing mixed chimerism (IMC) serves as an early indicator of disease recurrence.

Purpose of the Study:

• To evaluate the predictive value of chimerism testing for leukemia relapse.
• To assess the performance of increasing mixed chimerism (IMC) as a surrogate for disease activity.
• To analyze the sensitivity and specificity of chimerism monitoring in predicting relapse post-stem cell transplant.

Main Methods:

• Quantitative PCR and short-tandem repeat methods were combined for high-sensitivity chimerism analysis.
• A cohort of 184 patients undergoing stem cell transplant for leukemia (AML, ALL, MDS) was studied.
• 2389 chimerism tests were performed with a median follow-up of 1054 days.

Main Results:

• A significant increase in relapse risk was observed after one IMC (HR 9.9) or two or more consecutive IMCs (HR 44.4).
• The predicted relapse probability by day 30 post-IMC was 0% (no IMC), 10% (one IMC), and 40% (≥2 IMCs).
• Chimerism monitoring demonstrated 86.4% sensitivity and 91.6% specificity for relapse prediction, with identified causes for false positives (T-cell contamination) and false negatives (rapid relapse, extramural relapse).

Conclusions:

• Chimerism monitoring is a valuable tool for predicting leukemia relapse post-stem cell transplant.
• Interpreting IMC requires caution due to potential false positives and false negatives.
• T-cell removal strategies can enhance the specificity of chimerism testing in patients with mixed T-cell chimerism.