Abstract
Introduction: Myelodysplastic syndrome (MDS) is a hematologic disorder of ineffective hematopoiesis that can progress to acute myeloid leukemia (AML). Lung transplant recipients are at increased risk of MDS and AML due to prolonged immunosuppression, which weakens immune surveillance and promotes clonal evolution of abnormal hematopoietic cells. Low-risk MDS remains as a relative contraindication for lung transplant. We present two post-lung transplant cases of MDS progressing to AML, highlighting the complexity of managing immunosuppression and hematologic malignancy in this population. Description Case 1: A 70-year-old man underwent bilateral lung transplantation for chronic obstructive pulmonary disease, complicated by end-stage renal disease and antibody-mediated rejection. Despite a diagnosis of low-grade MDS, he was deemed very low risk of progression to AML by hematology before transplantation. Posttransplant, he was placed on tacrolimus, mycophenolate, and prednisone, but developed leukopenia and anemia, necessitating discontinuation of mycophenolate. Two years later, a surveillance bone marrow biopsy showed MDS with 4% myeloblasts and mild dyspoiesis. His condition slowly deteriorated despite supportive therapy and medication adjustments. Eight years after transplant, a bone marrow biopsy confirmed AML with 36.5% blasts with CD19 and CD34 expression and a p53 mutation. He began chemotherapy with decitabine, venetoclax, and vincristine. Description Case 2: A 72-year-old man diagnosed with low-grade MDS before transplant received a bilateral lung transplant for combined pulmonary fibrosis and emphysema. After transplant, he was maintained on tacrolimus, mycophenolate, and prednisone but experienced complications including septic shock due to methicillin resistant Staphylococcus aureus endocarditis. Three months after transplant, repeat bone marrow biopsy indicated MDS with 1.2% blasts and CD56+ monocytes. His condition worsened despite transfusions and luspatercept-aamt, progressing to AML with 24.1% blasts and mutations in U2AF1, NRAS, and SETBP1 and MECOM rearrangement. Chemotherapy with azacitidine and venetoclax was initiated, but he succumbed to diffuse alveolar hemorrhage. Discussion: Despite low risk MDS features, both patients in our report progressed to AML after lung transplant; their disease was resistant to conventional therapies. Further research on predictors of MDS progression after solid organ transplant and the impact of immunosuppressive medications on MDS disease progression is needed to help risk stratify older lung transplant candidates with low-risk MDS.