Observational Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 18, 2025; 15(2): 102671
Published online Jun 18, 2025. doi: 10.5500/wjt.v15.i2.102671
Clinical events and healthcare resource utilization associated with neutropenia and leukopenia among adult kidney transplant recipients receiving valganciclovir
Andrew P Beyer, Pamela A Moise, Michael Wong, Wei Gao, Cheryl Xiang, Pangsibo Shen, Martha Pavlakis, Flavio Vincenti, Weijia Wang
Andrew P Beyer, Weijia Wang, Department of Value and Implementation Outcomes Research, Merck & Co., Inc., Rahway, NJ 07065, United States
Pamela A Moise, Medical Affairs, Merck & Co., Inc., Rahway, NJ 07065, United States
Michael Wong, Scientific Affairs, Merck & Co., Inc., Rahway, NJ 07065, United States
Wei Gao, Cheryl Xiang, Pangsibo Shen, Analysis Group, Boston, MA 02199, United States
Martha Pavlakis, The Transplant Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States
Flavio Vincenti, The Transplant Services, University of California San Francisco, San Francisco, CA 94143, United States
Author contributions: Xiang C was responsible for data collection; Wang W, Beyer AP, Gao W, Xiang C, Shen P were responsible for analysis and interpretation of results; Wang W, Pavlakis M, Vincenti F, Beyer AP, Moise PA, Wong M, Gao W, Xiang C, Shen P were responsible for draft manuscript preparation; all authors reviewed the results and approved the final version of the manuscript.
Institutional review board statement: This research utilizes curated de-identified data. As such, this study is exempt from Institutional Review Board (IRB) review.
Informed consent statement: This research utilizes curated de-identified data. As such, informed consent is not required.
Conflict-of-interest statement: Beyer AP, Moise PA, Wong M, Wang W are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, United States and own stock/options in Merck & Co., Inc., Rahway, NJ, United States. Gao W, Xiang C, Shen P are employees of Analysis Group, Inc., which has received consulting fees from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, United States for the conduct of this study. Vincenti F received research grants and consulting honoraria from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Pavlakis M received research grants and consulting honoraria from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, United States, Vertex Pharmaceuticals, Transplant Genomics, Inc., and Memo Therapeutics AG.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Weijia Wang, Department of Value and Implementation Outcomes Research, Merck & Co., Inc., 126 E Lincoln Ave, Rahway, NJ 07065, United States. weijia.wang@merck.com
Received: October 25, 2024
Revised: December 9, 2024
Accepted: January 23, 2025
Published online: June 18, 2025
Processing time: 119 Days and 13.2 Hours
Abstract
BACKGROUND

Cytomegalovirus (CMV) prophylaxis with valganciclovir and ganciclovir is associated with elevated neutropenia and leukopenia risk in kidney transplant recipients, although the impact of these events on healthcare resource utilization (HCRU) and clinical outcomes is unclear.

AIM

To quantify clinical events and HCRU associated with neutropenia and leukopenia among adults receiving valganciclovir and/or ganciclovir post-kidney transplantation.

METHODS

Adult kidney transplant recipients receiving valganciclovir and/or ganciclovir prophylaxis were identified in the TriNetX database from 2012 to 2021. Patient characteristics were evaluated in the 1-year period pre-first transplant. HCRU and adjusted event rates per person-year were evaluated in follow-up year 1 and years 2-5 after first kidney transplantation among cohorts with vs without neutropenia and/or leukopenia.

RESULTS

Of 15398 identified patients, the average age was 52.39 years and 58.70% were male. Patients with neutropenia and/or leukopenia had greater risk of clinical events for CMV-related events, opportunistic infections, use of granulocyte colony stimulating factor, and hospitalizations (relative risk > 1 in year 1 and years 2-5). Patients with vs without neutropenia and/or leukopenia had higher HCRU in year 1 and years 2-5 post kidney transplantation, including the mean number of inpatient admissions (year 1: 3.47 vs 2.76; years 2-5: 2.70 vs 2.29) and outpatient visits (48.97 vs 34.42; 31.73 vs 15.59, respectively), as well as the mean number of labs (1654.55 vs 1182.27; 622.37 vs 327.89).

CONCLUSION

Adults receiving valganciclovir and/or ganciclovir prophylaxis post-kidney transplantation had greater risk of neutropenia and/or leukopenia, which were associated with higher clinical event rates and HCRU up to 5 years post-transplantation. These findings suggest the need for alternative prophylaxis options with lower myelosuppressive effects to improve patient outcomes.

Keywords: Clinical outcome; Healthcare resource use; Kidney transplant; Leukopenia; Neutropenia; Ganciclovir; Valganciclovir

Core Tip: This observational study examined the impact of neutropenia and leukopenia up to 5 years in kidney transplant recipients who received valganciclovir or ganciclovir as cytomegalovirus (CMV) prophylaxis. The results showed that neutropenia and/or leukopenia were associated with increased risks of CMV-related events, opportunistic infections, hospitalizations, and use of granulocyte colony-stimulating factor. Additionally, patients with neutropenia and/or leukopenia had higher healthcare resource utilization, including more inpatient admissions, outpatient visits, and labs. These findings highlight the need for alternative prophylactic treatments for CMV with fewer myelosuppressive effects to improve outcomes in kidney transplant recipients.