QT prolongation in patients with acute leukemia or high-risk myelodysplastic syndrome prescribed antifungal prophylaxis during chemotherapy-induced neutropenia

Leuk Lymphoma. 2019 Dec;60(14):3512-3520. doi: 10.1080/10428194.2019.1639165. Epub 2019 Jul 12.

Abstract

Benefits of serial electrocardiographic (ECG) monitoring to detect QT prolongation in patients with hematological malignancies remain unclear. This retrospective, single-center, study evaluated 316 adult acute leukemia and high-risk MDS patients who received 11,775 patient-days of voriconazole prophylaxis during induction chemotherapy. Of these, 37 patients (16.2%) experienced QTc prolongation. Medications associated with QTc prolongation included furosemide, haloperidol, metronidazole, mirtazapine, prochlorperazine, and venlafaxine. Hypokalemia and hypomagnesemia were also significantly associated with QTc prolongation (HR 3.15; p = .003 and HR 6.47, p = .007, respectively). Management modifications due to QTc prolongation included discontinuation of QT prolonging medications (n = 25), more aggressive electrolyte repletion (n = 5), and enhanced ECG monitoring (n = 3). One patient with multiple QT prolonging factors experienced possible Torsades de Pointes. Overall mortality was 15% with no cardiac-related deaths. Serial ECG monitoring during induction chemotherapy can be tailored proportionally to QT-prolonging risk factors. Management should include aggressive electrolyte repletion and avoidance of concurrent QT prolonging medications.

Keywords: QTc prolongation; Voriconazole; antifungal; cardiac arrhythmia; infection prophylaxis.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antifungal Agents / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Induction Chemotherapy
  • Leukemia / drug therapy*
  • Leukemia / pathology
  • Long QT Syndrome / chemically induced*
  • Long QT Syndrome / pathology
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / pathology
  • Neutropenia / chemically induced
  • Neutropenia / drug therapy*
  • Neutropenia / pathology
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Voriconazole / adverse effects*

Substances

  • Antifungal Agents
  • Voriconazole