A previously healthy 12-year-old female patient was diagnosed with non-metastatic high-grade osteosarcoma of the right tibia after evaluation for a 2-month history of knee pain. She underwent limb-sparing resection and was treated with doxorubicin/methotrexate/cisplatin, receiving a cumulative anthracycline dose of 450 mg/m2 over an 8-month period of treatment. Her end-of-therapy evaluation was negative for disease. An echocardiogram performed prior to initiation of chemotherapy showed normal cardiac anatomy and normal left ventricular (LV) size and function (ejection fraction [EF] 60% and fractional shortening [FS] 43%). During the course of chemotherapy, the EF (55-59%) and FS (30-35%) remained within the normal range, but were progressively decreasing from pre-chemotherapy. Upon completion of chemotherapy, the LV was mildly dilated with mildly depressed systolic function (EF 49%; FS 25%) by echocardiogram. At this time, serum B-type natriuretic peptide was elevated (415 pg/mL). The patient was asymptomatic and had no evidence of heart failure (HF) and was started on angiotensin-converting enzyme inhibitor (ACEi) therapy. Despite ACEi therapy, her LV systolic function continued to deteriorate, and digoxin and furosemide were initiated with the presence of symptoms. At 18 months after completion of chemotherapy, she was admitted for HF exacerbation requiring milrinone and intravenous diuretics. Her LVEF was severely decreased (15%) at this time. She was able to be transitioned back to oral medications (ACEi, digoxin, beta-blocker, and furosemide). She was discharged home and underwent a diagnostic catheterization 1 month later, which showed normal intracardiac pressures and pulmonary vascular resistance (2 Wu x m2). Four months later, 24 months after chemotherapy completion, the patient was again admitted for an acute on chronic HF exacerbation requiring milrinone therapy. Her echocardiogram at this time showed moderately diminished right ventricular function in addition to severely decreased LV function. At this point, the decision was made to evaluate her for pediatric heart transplant. During the counseling session, her parents ask you about the outcomes of pediatric heart transplant for anthracycline cardiomyopathy (ACM).
Which of the following is true regarding pediatric heart transplant for ACM?
Show Answer
The correct answer is: B. There is no difference in malignancy-related death after pediatric heart transplant for ACM compared with DCM.
Pediatric heart transplant is an accepted treatment option for end-stage HF after anthracycline exposure. In 2015, Bock et al. evaluated outcomes after pediatric heart transplant due to ACM against DCM using the United Network of Organ Sharing database and reported that there was lower long-term survival in the ACM cohort.1 However, Bock and colleagues recently presented a more comprehensive review of mortality and cancer recurrence in pediatric patients transplanted for ACM that found no difference in overall or graft survival using a matched cohort (1- and 5-year matched survivals of 92% and 74% versus 92% and 80% for the ACM and matched DCM cohorts, respectively [log-rank test p value = 0.37]).2 The patients were identified from the pediatric heart transplant study registry, which collects information on all children listed for heart transplant at 45 institutions in 3 countries and captures approximately 80% of worldwide heart transplant candidates. Children receiving heart transplant for ACM (62 subjects during the study period 1993-2014) were compared with those with DCM in a 2:1 matched cohort (matched for age at listing, sex, race, status at listing, and year of listing). No patient had primary cancer recurrence (all malignancies, 5 in 4 patients, were post-transplant lymphoproliferative disease). In addition, there was no difference in post-transplant malignancy occurrence between cohorts, and no malignancy-related deaths occurred. This is similar to outcomes that Lenneman and colleagues reported in 2013 from a review of all patients transplanted for ACM from the United Network of Organ Sharing registry where there was no difference in death from cancer between the ACM cohort and patients transplanted for other etiologies.3
Before outcome studies demonstrated the rare recurrence of primary malignancy, a 5-year cancer-free period before pediatric heart transplantation was recommended. However, as large follow-up studies have continued to show that there is no difference in post-transplant malignancy rates or death between patients with ACM and DCM, this recommendation is generally not accepted. The appropriateness of listing a pediatric patient for transplant must be individualized, but early listing after chemotherapy completion is considered acceptable in most cases.
References
Bock MJ, Sehgal S, Gambetta K, Marino BS, Backer CL, Pahl E. Pediatric Heart Transplantation for Anthracycline Cardiomyopathy: A UNOS Database Review. J Heart Lung Transplant 2015;34:S321.
Bock MJ, Pahl E, Rusconi PG, et al. Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: A report from the Pediatric Heart Transplant Study (PHTS) group. Pediatr Transplant 2017;21:e12923.
Lenneman AJ, Wang L, Wigger M, et al. Heart transplant survival outcomes for adriamycin-dilated cardiomyopathy. Am J Cardiol 2013;111:609-12.