Radiation-induced lymphopenia: A data compilation to unveil relevant factors and mitigation strategies

Radiation-induced lymphopenia (RIL) is a common complication of radiation therapy (RT) that can undermine antitumor immunity and diminish the efficacy of immunotherapy. While RIL is a known predictor of poor outcomes, its underlying mechanisms and key determinants remain poorly characterized.

We systematically compiled and quantitatively analyzed published data on absolute lymphocyte count (ALC) dynamics during and after RT. A total of 142 ALC curves from 52 publications were digitized and integrated into a standardized database. This database encompasses various RT modalities, including therapy with X-rays or charged particles, as well as extracorporeal irradiation of blood (ECIB).

Analysis revealed consistent lymphocyte depletion during treatment. By the end of RT, median ALCs declined to 24% (range: 1.5-78%) of baseline for intracorporeal exposure and 10% (range: 1-60%) for ECIB. Recovery was incomplete and cancer-type-dependent, reaching only a median of 55% (range: 33-90%) of baseline within one year. We identified baseline ALC, planning target volume (PTV), and dosimetric parameters as key predictors of severe lymphopenia. A low rate of lymphocyte depletion during treatment was frequently associated with impaired long-term recovery. Particle therapy was associated with an average 11% higher end-of-treatment ALC compared to photon therapy, underscoring the lymphocyte-sparing benefit of reduced integral dose.

This work establishes a comprehensive, quantitative foundation for understanding RIL. The developed ALC database supports mechanistic investigation and enables model-based approaches to predict lymphocyte dynamics, guiding the design of lymphocyte-sparing treatment strategies, including particle therapy.