Pre-neutropenic fever in patients with hematological malignancies: a novel target for antimicrobial stewardship

Abstract

Background Many patients with hematological malignancy develop fever after chemotherapy/conditioning but before chemotherapy-induced neutropenia (pre-neutropenic fever - PNF). The proportion of PNF with an infectious etiology is not well established. Methods We conducted a single center, prospective observational sub-study of PNF (neutrophils>0.5 cells/μl, ≥38.0°C) in adults receiving AML chemotherapy, or alloHCT conditioning enrolled in a neutropenic fever RCT between 1 January and 31 October 2018. Eligible patients had anticipated neutropenia ≥10 days and exclusions included concurrent infection and/or neutropenia prior to chemotherapy or conditioning commencement. PNF rates, timing and infections encountered were described. Associations between non-infectious etiologies and fever (thymoglobulin, haploidentical donor, cytarabine) were explored. Antimicrobial therapy prescription across pre-neutropenic and neutropenic periods was examined. Results Of 62 consecutive patients included (43 alloHCT, 19 AML), 27 had PNF (44%) and five (19%) had an infective cause. Among alloHCT, PNF occurred in 14/17 (82%) who received thymoglobulin; only 1/14 (7%) had infection diagnosed. During AML chemotherapy, 18/19 received cytarabine, of which 8/18 (44%) had PNF and 3/8 (38%) had infection. Most patients with PNF had empiric antimicrobial therapy continued into the subsequent neutropenic period (19/27, 70%). Those with PNF were more likely to be escalated to broader antimicrobial therapy at onset/during neutropenic fever (5/24 [21%] vs 2/30 [7%]). Conclusion Rates of PNF were high, and documented infection low, particularly among those receiving known fever-inducing treatments, leading to prolonged and escalating antimicrobial therapy. In the absence of evidence of infection, early cessation of empiric therapy after PNF is recommended as an important AMS intervention.