A case of myelodysplastic syndrome with extramedullary hematopoiesis followed by rapid transformation into NRAS-mutated acute myeloid leukemia in an orthotopic liver transplant recipient

Introduction: With the increase in lifespan and the resulting immunosuppression that decreases tumor surveillance, secondary malignancies in liver transplant recipients are becoming more common. Case Report: We present a unique case of a 33-year-old man who developed myelodysplastic syndrome with transformation into acute myeloid leukemia following orthotopic liver transplantation. Approximately 18 months after the patient’s liver transplantation, he developed leukopenia and neutropenia which shortly progressed into leukocytosis with peripheral blasts. His bone marrow aspirate showed 10% myeloblasts with the patient thereafter being diagnosed with myelodysplastic syndrome with excess blasts-2. Two months later, the patient had repeat flow cytometry of his blood which revealed 18% myeloblasts in the CD45 dim blast gate along with co-expression of CD34 and CD117, consistent with a diagnosis of refractory anemia with excess of blasts in transformation/acute myeloid leukemia. Next generation sequencing exhibited one variant of strong clinical significance in the neuroblastoma RAS viral oncogene homolog. The patient was not a candidate for allogenic stem cell transplantation and he expired approximately five months after diagnosis of acute myeloid leukemia despite two cycles of decitabine and venetoclax. Conclusion: This case demonstrates how complications of orthotopic liver transplantation including secondary malignancies are becoming more common and that the benefits and risks associated with chronic immunosuppressive therapy must be balanced against each other. The case also exhibits the heterogeneous nature of this phenomenon and that further work is needed to determine the optimal treatment for this post-liver transplant disease which unfortunately heralds a poor prognosis.