To the Editor,
Fever is a common complaint amongst children with an underlying oncologic diagnosis, especially during chemotherapy course and periods of neutropenia. It’s often necessitating presentation and hospitalization for evaluation of sepsis. However, the cause(s) of the fever is not usually clear [Lehrnbecher 2019]. Chemotherapy induced fever is well described in relation to specific chemotherapy agents. However, fever induced by vincristine (VCR) has only been rarely reported [Ishii et al 1988 and Imai et al 2001], and the prevention and management are not well established yet. We describe a case of recurrent VCR-induced fever that was controlled with dexamethasone and Tylenol.
Our patient is a 5-year-old female with stage III Wilms tumor who was initiated on DD4A chemotherapy. She repeatedly developed fever within 24 hours after receiving chemotherapy from week 1 to 4 of treatment, where she received VCR as a single agent or in combination with other agents. As per institutional guidelines, the patient was hospitalized for evaluation of underlying sepsis with each fever 4 weeks consecutively. Fevers were high grade and lasting up to 48 hours. During fever episodes, Her Absolute neutrophil count nadir was 700 K/CUMM (range 700-5000), and there were no other associated clinical symptoms, and laboratory tests remained stable with normal white blood cell count and differential, and negative septic work up and blood cultures.
Anticipating an underlying allergic reaction, we subsequently prophylactically administered dexamethasone 3 mg/m2/dose IV along with Acetaminophen 15mg/kg/dose PO one dose each prior and 12 hours after Vincristine administration. Thereafter, the chemotherapy course including weekly VCR was uneventful and there were no reported fevers.
The pathophysiology behind this phenomenon is not well established yet. Imai et al suggested that an allergic response to VCR might be involved when investigating recurrent fever in a 2 year old patient with rhabdomyosarcoma after receiving VCR including chemotherapy. Leukocyte migration testing (LMT) was performed which showed that migration index with VCR added with the patient’s serum was significantly higher compared to normal controls. These findings indicated the possibility of an underlying delayed cell-mediated hypersensitivity to VCR.
Ishii et al reported that more than two VCR-induced fever episodes were identified in 9 of 31 children with leukemia or lymphoma undergoing maintenance chemotherapy. Similarly, they reported that the duration of fever was shortened with corticosteroids suggesting the possibility of an allergic reaction mechanism behind it.
Interestingly, this appears to be a rare phenomenon, given the wide application of Vincristine in adult and pediatric chemotherapy protocols and the scarcity of reports in the literature. A such, we hope to support previous reports with our individual experience. In patients developing recurrent fever following chemotherapy with VCR, febrile allergic reaction and prophylactic treatment should be considered after exhaustion of appropriate investigations.