Next-Generation Sequencing Analysis in Posttransplant Relapsed Acute Myeloid Leukemia Reveals Clonal Evolution and Donor-Derived Germline Variant Indicating Bone Marrow Chimerism

The era of next-generation sequencing (NGS) has led to a deeper understanding of the genetic complexity and heterogeneity of this disease, in addition to revealing mechanisms of disease relapse. Clinical NGS is becoming routine in clinical practice in both solid organ and hematologic malignancies to identify molecular markers of disease that might assist with diagnosis, prognosis, and the treatment of cancer. These tumor-specific markers also enable treatment response monitoring, as they serve as clonal markers unique to the disease. Continuous molecular monitoring also allows identification of disease recurrence with potentially new actionable mutations. This practice is complicated in the setting of allogeneic bone marrow transplant, as the admixtures of donor and recipient DNA pose unique challenges to NGS interpretation. This case highlights the importance of systematic methodological interpretation of NGS results to better understand the clinical significance and impact of new mutations discovered posttransplant and reveals another potential application of NGS for bone marrow engraftment analysis.