Introduction: Heart transplant (HTx) has been performed for childhood cancer survivors with end stage heart failure, yet there is no consensus for timing of candidacy.  Many centers require time frame of 2 years after chemotherapy completion to become eligible for HTx. However, for patients who develop severe acute or early onset chronic cardiotoxicity from anthracycline therapy, earlier consideration may be warranted. The purpose of the case series is to describe our center’s experience with management and outcomes of five children who developed early anthracycline cardiotoxicity and required HTx prior to 2 years after chemotherapy completion.
Methods: A retrospective chart review was performed of all HTx recipients with anthracycline cardiotoxicity performed at our institution between 1988 to 2022.
Results: Of the 411 patients transplanted at our institution, 12 underwent HTx due to heart failure from anthracycline cardiotoxicity.  Five children with cancer developed decompensated heart failure early while undergoing chemotherapy and underwent HTx less than 2 years prior to chemotherapy completion. Cancer diagnoses included acute lymphoblastic leukemia (n= 3), acute lymphoblastic leukemia with extramedullary relapse (n=1), and osteosarcoma (n=1).  Three patients were male.  Median anthracycline dose was 285 mg/m2 (IQR 240-330).  Decision to offer HTx involved collaboration with family, oncology, cardiology, and ethics teams to assess goals of care, risk for recurrence, patient and graft survival, and to ensure that principles of utility and justice were considered.  
Two patients developed cardiogenic shock within 6 months of chemotherapy and required VAD (n=1) and ECMO (n=1) as bridge to HTx.  Three required milrinone. One required implantable cardioverter defibrillator due to malignant arrhythmias.   Median time from last chemotherapy session to HTx was 6 months (IQR: 0.9-7.5).  All are surviving with median survival time of 15 years (10.5-18.5). Post-transplant related morbidities included Grade 2R cellular rejection 2 months after HTx (n=1), PTLD 7.5 years and 10 years after HTx (n=2) , and cardiac allograft vasculopathy 10 years after Htx for which patient underwent re-transplant (n=1).   No patients developed infections or malignancy recurrence.  When compared to patients who underwent HTx later at least 2 years after chemotherapy completion, there was no difference in median survival time (p = 0.8), PTLD (p = 0.6), or CAV (p =1.0).
Conclusions: These cases illustrate that HTx performed before 2 years of chemotherapy completion is feasible and can offer improved survival for select children with end stage heart failure and cancer.  With collaboration between oncology, cardiology and ethics, criteria for HTx and advanced heart failure therapies should be individualized by malignancy type, response to treatment, and risk for recurrence.