Management Blueprint for Acquired Long QT Syndrome in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

Abstract

Background Acquired long QT syndrome is a well-described pathology in the pediatric population. Previous publications demonstrated that patients undergoing hematopoietic stem cell transplantation (HSCT) can develop cardiac complications, and several of these patients develop drug-induced long QT syndrome in the post-transplant period. Previous publications suggest that HSCT patients present significant QT prolongation in the early post-transplantation period. Patients and methods A database including 193 HSCT performed in 172 pediatric patients at the UCLA Mattel Children's Hospital between January 2007 and December 2017 was queried to identify patients diagnosed with long QT syndrome in the work-up for HSCT, during the transplantation procedure, or in the post-transplantation follow-up. A retrospective review was conducted which classified patients by primary diagnosis, pre-engraftment viral serology, transplant graft, donor match status, time to engraftment, treatment drugs and demographic data, with primary focus at QT values both pre and post-transplantation as well as correlations with current drug exposures at the time as well as treatment changes made directly following diagnosis of prolonged QT. Results Out of 172 patients reviewed, only 153 had adequate ECG documentation available. Thirty-four patients (22.2%; 19 males, 15 females) were diagnosed with prolonged QT before (4 male patients, 2.6%), during or after HSCT, as per the guidelines from the American Heart Association/American College of Cardiology (AHA/ACC) defining an abnormally long QTc interval as >470 milliseconds in post-pubertal males and >480 milliseconds in post-pubertal females, or a QTc >460 milliseconds in patients under 15 years of age. The main drugs implicated with QT prolongation in these patients were antiemetics (diphenhydramine and ondansetron), antimicrobials (fluconazole, foscarnet, pentamidine, posaconazole, trimethoprim/sulfamethoxazole and voriconazole), tacrolimus and methadone. After recognition of the QT prolongation, careful choice of drugs to be used, with adequate switches whenever possible, dose decrease of unavoidable drugs, prompt management of electrolyte imbalances and weekly electrocardiographic monitoring led to reduction of the QT intervals. Conclusion Normalization following interventions suggest that options do exist for appropriate diagnosis and management of acquired long QT syndrome in pediatric patients undergoing HSCT. A management blueprint is proposed based on our experience at Mattel Children's Hospital for acquired long QT given the clinical implications known to this syndrome.