PS1531 INCIDENCE, RISK FACTOR AND OUTCOME OF IMMUNE‐MEDIATED NEUROPATHIES FOLLOWING HAPLOIDENTICAL HAEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Ren X. , Liu X. , Huang Q. , Wang Q. , He Y. , Zhu X. , Han W. , Chen H. , Chen Y. , Wang F. , Wang J. , Zhang Y. , Mo X. , Chen Y. , Wang Y. , Fu H. , Chang Y. , Xu L. , Liu K. , Huang X. , Zhang X. 
Published: June 2019

Background:Haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) has given rise to an increasing number of neurological complications that cause high morbidity and mortality. Our previous studies have characterized central nervous system complications (Ann Hematol, 2018), although the relatively rare peripheral neuropathies remain poorly understood. Apart from those with clear etiologies, such as treatment toxicity and tumor infiltration, a small subset of posttransplant neuropathies known as immune‐mediated neuropathies (IMNs) is solely relevant to immune factors. Recently, new insights have been proposed for posttransplant IMNs; for instance, diseases such as radiculoplexus neuropathies and multiple mononeuropathies can also be IMN subtypes, which previously included only Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) (J Neurol Neurosurg Psychiatry, 2014). However, the IMNs complicating haplo‐HSCT have not been systematically elucidated at present.Aims:To investigate the incidence, clinical features, risk factors and outcomes of IMNs complicating haplo‐HSCT.Methods:A nested, case‐control study was performed based on 3858 patients who received haplo‐HSCT at Peking University People's Hospital. Transplantation was conducted according to our previous protocols. Cases were defined as patients who developed IMNs after haplo‐HSCT, which were identified by chart review of clinical manifestations, laboratory findings, electrodiagnostic studies, and radiological findings. Individual matching was performed by randomly selecting 3 controls for each identified case from the same cohort considering the time of HSCT (± 90 days), gender, and follow‐up time (± 180 days).Results:Forty cases of IMNs were identified from 3858 haplo‐HSCT patients, for an incidence rate of 1.04%. The median onset time of the IMNs was 78 days after haplo‐HSCT. The identified IMN cases included 10 GBS and 30 peripheral neuropathies that did not meet the diagnostic criteria for GBS or CIDP. The main clinical manifestations were weakness (57.5%), altered sensation (57.5%), hyporeflexia (25%) and pain (10.0%). In the univariate analysis, aGVHD (P = 0.116), cGVHD (P = 0.024), and CMV viremia (P = 0.024) were identified as potential risk factors (P < 0.20) for IMNs. However, only CMV viremia (HR = 4.557, P = 0.024) was identified as an independent risk factor after multivariate analysis. No significant differences in OS (P = 0.619), DFS (P = 0.609), NRM (P = 0.87) or the incidence of relapse (P = 0.583) were found between posttransplant patients with and without IMNs. Eleven (27.5%) of the IMN patients developed cGVHD, which was a significantly higher incidence than that of the patients without IMNs (P = 0.012). All IMN patients received vitamin B1 and B12 therapy once a diagnosis of IMNs was suspected, and 6 of them achieved neurological improvement without further treatment. IVIG/steroids were given to 25 IMN patients, of whom 18 (72%) subsequently achieved clinical improvement.Summary/Conclusion:CMV viremia is the only independent risk factor for rare posttransplant IMNs. Haplo‐HSCT patients with IMNs are at a higher risk of developing cGVHD. Vitamin B and IVIG/steroids can help improve neurological outcomes. In the future, prospective multicenter studies are needed to increase our understanding of the underlying pathogenesis and to propose standardized diagnostic and therapeutic strategies.