Fever with Significant Procalcitonin Increase Following Gemtuzumab Ozogamicin Infusion in Hematologic Malignancy Patients without Evidence of Infection
Authors: Kubara Chiaki , Shima Takahiro , Mori Yasuo , Kato Koji , Akashi Koichi 
Published: December 2023

In patients diagnosed with hematologic malignancies, including acute myeloid leukemia (AML), infections remain a major cause of non-relapse mortality. The accurate detection and management of infections during the treatment of these diseases are crucial for successful outcomes. Procalcitonin (PCT) has been proposed as a valuable tool for identifying severe bacterial infections, even in patients with hematologic malignancies.

Gemtuzumab ozogamicin (GO), a humanized anti-CD33 monoclonal antibody conjugated to calicheamicin, is used in certain subsets of AML patients, such as core binding factor (CBF) leukemia and AML with favorable-risk, as well as in cases of refractory AML. However, GO administration comes with its own set of risks, including liver dysfunction, veno-occlusive disease (VOD), bone marrow suppression, bleeding, and infusion reactions. Among these reactions, those causing high fever and shivering can be particularly challenging to differentiate from sepsis or severe infections. Nevertheless, there have been no reports evaluating the utility of PCT in discriminating infections during GO-induced infusion reactions.

To shed light on the impact of GO administration on PCT levels, we undertook a retrospective analysis. Over the period between 2014 and 2022, we administered GO (3.0 mg/sqm per dose) to 42 patients with hematologic malignancies, a total of 97 times (median 2 doses per patient, range 1-6 doses per patient). Of the recipients, 23 had undergone allogeneic stem cell transplantation, while 19 were non-transplant patients. Prior to GO administration, all patients received premedication comprising corticosteroids, antihistamines, and acetaminophen. Among the 97 instances of GO administration, 40 (41.2%) resulted in fever (≥37.5 ℃) within 24 hours.

For 19 cases, we conducted a complete set of PCT measurements and blood cultures within 24 hours of GO administration and analyzed the PCT levels and clinical parameters. These 19 cases corresponded to 19 individual patients, of whom nine had CBF leukemia, including t(8;21) AML or inv(16) AML, and ten had non-CBF leukemia. Out of these patients, 12 experienced fever (≥37.5 ℃), while seven did not. The findings indicated that patients with fever (≥37.5 ℃) exhibited significantly higher PCT levels compared to afebrile patients (p=0.018). Furthermore, PCT levels showed a significant positive correlation with C-reactive protein levels (p=0.003). However, among the 19 patients, only one patient with a positive PCT result had a documented infection identified through blood cultures or imaging studies.Other factors, such as patient gender (p=0.467), underlying disease (p=0.224), disease remission status at GO administration (p=0.492), transplant status (p=0.556), and the number of GO administrations (p=0.906), did not significantly influence PCT levels.

It is essential to acknowledge that this analysis is based on a limited number of cases from a single institution. Nevertheless, approximately 40% of patients experienced fever within 24 hours of GO administration, despite receiving premedication.Furthermore, the presence of fever after GO administration was associated with a significant increase in PCT levels, even in the absence of identifiable infection. This raises the possibility of false positives for PCT in the context of GO-induced infusion reactions, underscoring the need for cautious interpretation of PCT values for infection differentiation in patients undergoing regimens that include GO. Further research with larger patient cohorts is warranted to validate these findings and improve our understanding of the implications of PCT measurements in this clinical setting.