Neurological Complications In Chinese Children Undergoing Hematopoietic Stem Cell Transplantation (hsct)

Abstract

Background and Aims: HSCT is a curative strategy in a variety of benign and malignant pediatric disorders. Neurological complications could result in significant morbidity and might impact survival. We perform a review for the burden of neurological complications in local pediatric HSCTs. Method: Retrospective review of consecutive HSCTs performed in a tertiary pediatric unit from 2007-2016. Neurological symptoms and complications occurring from start of conditioning to 6m after HSCT were included. Underlying demographics, HSCT indications, regimens and outcomes were studied for risk factors and impact on survival evaluated. Results: 196 HSCT episodes were included, with median age at HSCT being 6.3y (range: 0.3–20.6). Indications of HSCT included leukemia/lymphoma in 85 (43%), benign hematological/immunological disorders in 56 (29%), CNS tumors in 12 (6%), non-CNS solid tumors in 43 (22%). 144 episodes (74%) were allogeneic while 52 (26%) were autologous. Stem cell source was BM in 57 (29%), CB in 65 (33%) and PBSC in 74 (38%). For episodes of allogeneic HSCT, donors were matched-unrelated in 82 (42%), matched-siblings in 38 (19%) and haploidentical in 24 (12%). CNS complications developed in 33 (17%) HSCT episodes. Symptoms of presentation included alteration in consciousness (n=7), seizure (n=9), headache (n=16), motor deficits (n=10), visual disturbances (n=9), sensory dysfunction (n=2), and others (n=8). Etiologies of these complications were attributed to primary disease in 9, drug effects in 5 (including PRES in 3), stroke/ICH in 4, infection in 3, and radiotherapy (RT) effect in 2 and hypocalcemia in 1. Neurological complications were significantly associated with indications of HSCT (leukemia/lymphoma = 21%; benign hematological/immunodeficiency 14%; CNS tumors 42%; Non-CNS solid 5%; p=0.01); pre-HSCT CNS involvement by underlying disease (No involvement = 13% vs disease involvement = 39%; p=0.001), and RT-containing conditioning regimen (no RT = 13% vs RT-containing = 28%; p=0.018). Pre-HSCT CNS directed treatment, stem cell source, donor type, busulphan/cyclosporin use were not significantly associated with CNS complications. Upon multivariate analysis, pre-HSCT CNS involvement by underlying disease remained to be the only significant factor (p=0.019). When analysis was limited to allogeneic HSCT episodes, CNS complications were still associated with CNS involvement by underlying disease (p=0.011) and TBI/TLI-containing conditioning (p=0.029). HSCT episodes with CNS complications were associated with inferior outcome (2y OS 53.9%±8.8% vs 63.8%±4.2%; p=0.016). Conclusion: Neurological complications were common in pediatric HSCTs and had adverse impact on survival. Etiologies were multifactorial with pre-HSCT CNS involvement by underlying disease and radiation during conditioning being risk factors.