Non-Infectious Fever During Engraftment Following Autologous Hematopoietic Stem Cell Transplantation: Does Plerixafor Play a Role?

Introduction: Patients undergoing hematopoietic stem cell transplant (HSCT) commonly develop a variable constellation of signs and symptoms around the time of bone marrow recovery, which has been termed engraftment syndrome (ES). This is thought to reflect a systemic inflammatory state corresponding with reconstitution of immune cells, associated with cytokine release and capillary leakage. The presentation is highly variable, with a range of manifestations including fever, erythematous maculo-papular skin rash, noncardiogenic pulmonary edema, weight gain, diarrhea, liver and renal dysfunction, and encephalopathy. Fever, with or without other features of ES, is a significant event in the pre-engraftment phase of ASCT in that it can lead to additional diagnostic testing, empiric antibiotic therapy, and other changes in management. Several predisposing factors for ES have been proposed. One possible factor is exposure to plerixafor, a CXCR4 agonist that is being increasingly used for mobilization of hematopoietic stem cells. Objective: To determine if the use of plerixafor during mobilization of stem cells play a role in the devepment of engraftment fever. Methods: We retrospectively reviewed Medical records from of all patients who underwent an autologous HSCT at the Audie L. Murphy Memorial VA Hospital between 2011 to 2015. Data were gathered on the use of plerixafor for mobilization of cells, transplant diagnosis, conditioning regimen, number of CD34 + and nucleated cells infused, timing of fever, timing of engraftment (defined as recovery of peripheral neutrophil count above 500 cells per microliter), and length of hospital stay. Peri-engraftment fever was defined as temperature >100.4 F with onset between four days prior to and two days after engraftment, with negative infectious workup. Results: 255 patients underwent an autologous HSCT between 2011 to 2015. Of those, 162 (64%) patients developed fever, and 90 (35%) met our criteria for peri-engraftment fever. All patients received filgrastim, and 128 (50%) also received plerixafor for stem cell mobilisation. No association was found between use of plerixafor and peri-engraftment fever (OR .804, 95% CI .480-1.345, P = .405). The doses of nucleated cells (OR .967, CI .926-1.011, P = .136) and CD34 + stem cells (OR .996, CI .908-1.093, P = .935) infused did not correlate with peri-engraftment fever. Patients 60 years of age or older were more likely to develop peri-engraftment fever than younger patients (OR 1.833, CI 1.045-3.214, P = .034). Peri-engraftment fever was also more common in patients with multiple myeloma than those with other diagnoses (OR 2.189, CI 1.164-4.116, P = .015). Conclusion: The use of plerixafor does not appear to increase the risk of fever during engraftment following autologous HSCT in the population studied.