Role of G-CSF after High-Dose Post-Transplantation Cyclophospamide

Abstract

<h3>Background</h3> High-dose post-transplantation cyclophosphamide (PTC) has proven to be a valuable treatment modality for the prevention of graft-versus-host disease (GVHD) after stem cell transplant (SCT). Granulocyte colony stimulating factor (G-CSF) is routinely given after PTC to improve time to engraftment. Historically, G-CSF is given on Day +5 post-SCT. However, this strategy has not been vigorously compared to other dosing strategies. We sought to assess the effect of delayed (Day +10) or omitted administration of G-CSF on various post-SCT outcomes. <h3>Methods</h3> Allogeneic SCT patients receiving PTC at standard dosing of 50 mg/kg daily on Days +3 and +4 were included in this retrospective analysis. G-CSF was given at the labeled dose of 5 mcg/kg (rounded to nearest vial) on Day +10 for 15 consecutive patients then omitted entirely for 31 consecutive patients. These results were compared to historical controls that received G-CSF beginning Day +5 after PTC. All patients received antimicrobial prophylaxis with levofloxacin, acyclovir and posaconazole. The primary outcome was to determine time to engraftment, defined as an absolute neutrophil count ≥500, in each group. A complete list of secondary outcomes is below and includes febrile neutropenia and infection rates, incidence of acute GVHD, as well as survival and relapse rates. <h3>Results</h3> Sixty-eight patients were included in the final analysis. Patient characteristics and outcomes are described in Table 1. There were no significant differences between the three groups with the exception of cells infused (p=0.04). Patients not receiving G-CSF post-transplant were associated with a statistically significant longer time to engraftment than those receiving G-CSF (22 vs. 18 days; p=0.04). There were no significant differences in all other outcomes. First year relapse and mortality were unable to be determined at this time for patients not receiving G-CSF due to this population not reaching these endpoints at time of submission. <h3>Conclusion</h3> Administration of G-CSF after post-transplant cyclophosphamide is associated with earlier neutrophil engraftment (22 vs. 18 days; p=0.04). There was no difference in time to neutrophil engraftment in patients receiving G-CSF on Day +5 vs. 10. Secondary endpoints including platelet engraftment, aGVHD, incidence of febrile neutropenia, or infections were similar among all groups. A larger, randomized study is needed to confirm these results.