Treatment of Central Nervous System Viral Infections after Allo-HSCT with Intrathecal Donor Lymphocyte Infusion: Feasibility Analysis

Objective To investigate the efficacy and safety of intrathecal donor lymphocyte injection (IDLI) in the treatment of central nervous system virus infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The clinical data of 32 patients with central nervous system virus infection after allo-HSCT treated with IDLI from May 2014 to February 2024 were retrospectively analyzed. Once the central nervous system virus infection was diagnosed, the patient or his family signed the IDLI treatment consent. The mononuclear cells were isolated from 10~20ml of peripheral blood of the original donor or a third immediate family member under strict aseptic conditions, then IDLI was performed once or twice a week, until the virus in cerebrospinal fluid turns negative by PCR and/or mNGS. Results In terms of donor lymphocyte origin, 27 cases were from the original donor and 5 were from a third immediate family member. A total of 125 times IDLI were given. The first IDLI was on day 97(40-1946) after allo-HSCT. The median number of cycles of IDLI was 3(1-12), median number of mononuclearcell in a single IDLI was 2.7 (1.25-3.18)×10⁷, median duration of IDLI was 16 days (6-84). All 32 cases (100%) had an objective response, with best overall response of complete response in 21 (65.6%), partial response in 11(34.4%), median time to complete response was 17 days (8-77) after IDLI. A total of 12 (37.5%) patients died, none of the causes of death was CNS virus infection. Median follow-up was 201 days (2-3560), the 1-year overall survival rate was 60.1%, only 1 patient developed chronic graft-versus-host disease after the 12th IDLI treatment, and no immediate or long-term adverse reactions were observed in the other patients. Conclusion IDLI provides clinical benefit in patients with central nervous system virus infection after allo-HSCT, with high safety. These data represent a transformative and accessible treatment advance for patients with central nervous system virus infection after allo-HSCT with few treatment options.

No relevant conflicts of interest to declare.