Incidence and Risk Factors for Neutropenia in Adult Heart Transplant Recipients: Single Centre Experience.

PURPOSE: Neutropenia, a major complication of solid organ transplantation, is associated with poorer clinical outcomes. It has frequently been attributed to drug-induced bone marrow suppression and infections. Neutropenia in adult heart transplant recipients are increasingly observed, but little has been published on the burden of post-transplant neutropenia in this population. This study aims to characterise the incidence and identify the risk factors associated with neutropenia in adult heart transplant recipients.

METHODS: A retrospective medical records review was performed for all heart transplant cases between January 2010 and December 2018. Patients aged <18 years at transplant or died within 30 days of transplant were excluded. Neutropenia was defined as 2 consecutive absolute neutrophil count (ANC) ≤2.0 × 109 /L. Recurrent neutropenia was defined as ≥2 episodes of neutropenia ≥30 days apart.

RESULTS: Among 166 patients, 89 (53.6%) developed ≥1 episode of neutropenia during follow-up period and 35 (21.1%) had recurrent neutropenia. Median time to first-onset neutropenia was 81 days (IQR 58 - 196), with the majority (49/89; 55.1%) occurring within first 3 months after transplantation. The cumulative incidence of first-onset neutropenia at 3, 6 and 12 months were 31.1%, 39.7% and 50.1%, respectively. A total of 155 neutropenic episodes occurred during the study period. The median ANC nadir was 1.1 × 109 /L (IQR 0.6 - 1.5), and the median duration of neutropenia was 28 days (IQR 11 - 84). The median time to onset correlated with the severity of each neutropenic episode (rs = -0.362, p=0.000). Within 3 months post-transplant, the combination of poor renal function (eGFR <15 mL/min/1.73m2 and/or renal replacement therapy) and doses of mycophenolate mofetil exceeding 1000 mg/day at day 30 predisposed patients to first-onset neutropenia (OR 3.383, 95% CI 1.544 - 7.410), whereas cytomegalovirus (CMV) D-/R- status conferred a protective effect (OR 0.154, 95% CI 0.038 - 0.621). In contrast, CMV D+/R- status remained as the only significant predictor of first-onset neutropenia after 3 months post-transplant (OR 3.786, 95% CI 1.201 - 11.929).

CONCLUSION: Neutropenia is common amongst adult heart transplant recipients, particularly within 3 months post-transplant. Predictors of first-onset neutropenia varied at different time periods following transplantation.