Peripheral Neuropathy After Allogeneic Hematopoietic Stem Cell Transplantation: Incidence, Risk Factors, and...

Peripheral neuropathy (PN) is an uncommon but clinically significant complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, the incidence, clinical features, risk factors, and electrophysiological characteristics of PN remain unclear. To determine the incidence and risk factors of post-transplant PN (PTPN) and characterize its electrophysiological features using nerve conduction studies (NCS). We retrospectively analyzed consecutive patients aged ≥16 years who underwent first allogeneic HSCT at the Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital between January 2010 and December 2022. The primary endpoint was cumulative PTPN incidence. The cumulative incidence of PTPN was estimated with death treated as a competing event. Overall survival (OS) after PTPN onset was estimated using the Kaplan-Meier method. Risk factors for PTPN were evaluated using univariate and multivariate analyses using the Fine-Gray hazard model. Acute and chronic graft-versus-host disease (GVHD) were analyzed as time-dependent covariates. NCS findings were reviewed to characterize electrophysiological features and identify factors associated with reduced conduction parameters. Among 1332 patients who underwent HSCT, 57 developed PTPN. The 3-year cumulative incidence was 3.9% (95% confidence interval [CI], 2.9 to 5.1). Median time from HSCT to PTPN onset was 195 days (range, 11 to 1917). At PTPN onset, motor weakness and sensory disturbances were observed in 51 (89.5%) and 53 (93.0%) patients, respectively. Among 20 patients treated with intravenous immunoglobulin and/or methylprednisolone pulse therapy, only 2 (10.0%) showed symptomatic improvement. Multivariable analysis identified re-transplantation (hazard ratio [HR], 1.87; 95% CI, 1.05 to 3.34), grade II to IV acute GVHD (HR, 2.32; 95% CI, 1.34 to 4.00), and extensive chronic GVHD (HR, 4.27; 95% CI, 2.18 to 8.36) as independent risk factors for PTPN. Median survival after PTPN onset was 218 days (range, 5 to 3106), and the 3-year overall survival rate after PTPN onset was 33.0% (95% CI, 20.9 to 45.6). NCS was performed in 55 patients and 53 (96.4%) showed axonal-type neuropathy. Motor and sensory amplitudes were generally lower in the lower extremities than in the upper extremities. Median ulnar motor nerve conduction velocity and compound muscle action potential amplitude were 47.7 m/s and 3.4 mV, respectively, whereas the corresponding tibial values were 37.6 m/s and 2.2 mV. Median ulnar sensory nerve conduction velocity and sensory nerve action potential amplitude were 48.4 m/s and 12.2 μV, respectively, whereas the corresponding sural values were 42.7 m/s and 4.2 μV. Older age (≥50 years), male sex, re-transplantation, and PTPN onset within 200 days after HSCT were associated with reduced nerve conduction velocities or amplitudes. PTPN was associated with GVHD and re-transplantation and was characterized predominantly by axonal neuropathy. The electrophysiological pattern suggests that PTPN may represent a distinct neurological complication rather than classical immune-mediated demyelinating neuropathy. Further studies are needed to clarify its pathophysiology and develop transplant-specific diagnostic and treatment strategies.