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

Jason N. Barreto, Michael W. Cullen, Kristin C. Mara, Meagan E. Grove, Amanda G. Sierzchulski, Nathan J. Dahl, Pritish K. Tosh, Ross A. Dierkhising, Mrinal M. Patnaik, Michael J. Ackerman

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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.

Original languageEnglish (US)
JournalLeukemia and Lymphoma
DOIs
StatePublished - Jan 1 2019

Fingerprint

Myelodysplastic Syndromes
Neutropenia
Leukemia
Drug Therapy
Induction Chemotherapy
Electrolytes
Prochlorperazine
Torsades de Pointes
Hypokalemia
Metronidazole
Furosemide
Haloperidol
Hematologic Neoplasms
Mortality

Keywords

  • antifungal
  • cardiac arrhythmia
  • infection prophylaxis
  • QTc prolongation
  • Voriconazole

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

QT prolongation in patients with acute leukemia or high-risk myelodysplastic syndrome prescribed antifungal prophylaxis during chemotherapy-induced neutropenia. / Barreto, Jason N.; Cullen, Michael W.; Mara, Kristin C.; Grove, Meagan E.; Sierzchulski, Amanda G.; Dahl, Nathan J.; Tosh, Pritish K.; Dierkhising, Ross A.; Patnaik, Mrinal M.; Ackerman, Michael J.

In: Leukemia and Lymphoma, 01.01.2019.

Research output: Contribution to journalArticle

Barreto, Jason N. ; Cullen, Michael W. ; Mara, Kristin C. ; Grove, Meagan E. ; Sierzchulski, Amanda G. ; Dahl, Nathan J. ; Tosh, Pritish K. ; Dierkhising, Ross A. ; Patnaik, Mrinal M. ; Ackerman, Michael J. / QT prolongation in patients with acute leukemia or high-risk myelodysplastic syndrome prescribed antifungal prophylaxis during chemotherapy-induced neutropenia. In: Leukemia and Lymphoma. 2019.
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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.",
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