Don't Go Breakin’ My Heart: Lack of Association between Granulocyte Colony Stimulating Factor and Development of Acute Cellular Rejection

Abstract

Purpose Neutropenia commonly occurs after heart transplantation (HT) and granulocyte colony-stimulating factor (GCSF) may be used for treatment of neutropenia in this setting. Published data is lacking on the incidence and etiology of neutropenia, and the safety of GCSF with respect to subsequent risk of acute rejection. Methods This was a retrospective study in adult HT recipients from 2012-2018 at a single institution. All patients who received at least one dose of GCSF were identified and compared with patients without a history of therapy in the first year of HT. Patients were evaluated for acute cellular rejection (ACR) ≥2R within 3 and 12 months after GCSF. This was compared with the incidence of ACR in the non-GCSF group starting 4.5 months after HT (as the mean time to first neutropenic episode was 142 days in the GCSF group). Categorical variables were compared using the chi-square test. Results Of the 211 recipients included in the overall cohort, 71.1% were male, 58.3% were Caucasian, and 24.2% had ischemic cardiomyopathy. Mean age was 52.5 ± 12.1 years. In this cohort, 71 (33.6%) developed 136 episodes of neutropenia (mean 1.9 episodes/patient) requiring at least one dose of GCSF. Moderate (ANC 501-999/mcL) and severe (ANC ≤500/mcL) neutropenia was seen in 41.9% and 25% of cases, respectively. 78.9% of neutropenic cases were thought to be medication related based on chart review. Nearly all patients were induced with ATG (94.3%) and 24.6% were primary mismatch for cytomegalovirus. Each cycle of GCSF required on average 3.4 doses, with a mean total dose of 18.8 mcg/kg. The mean ANC nadir and peak was 850 ± 580/mcL and 7,520 ± 5,210/mcL, respectively. The mean time from HT to first neutropenic episode was 142 ± 100 days. Incidence of ACR ≥2R within the first 3 and 12 months was not significantly different between the GCSF (3 mo.: 9.9% and 12 mo.: 14.1%) and non-GCSF groups (3 mo.: 4.3% and 12 mo.: 18.6%) (p>0.05). Conclusion In this study, GCSF treated neutropenia occurred in one-third of patients within the first year after HT. GCSF does not appear to increase subsequent risk of ACR within the first year after GCSF administration.