Abstract
<title>Abstract</title> <p>Background Cannabis use is increasingly common among persons with multiple sclerosis (MS), yet its potential influence on hematopoietic stem cell mobilization, hematological recovery and neurological disability outcomes remains unclear. Autologous hematopoietic stem cell transplantation (aHSCT) represents an effective therapeutic option for patients with highly active or treatment-refractory MS. Objective To evaluate the association between cannabis exposure and CD34⁺ progenitor cell mobilization, early hematologic recovery of leukocytes, neutrophils, lymphocytes and platelets, and post-transplant disability assessed by changes in the Expanded Disability Status Scale (EDSS) in patients with MS undergoing autologous HSCT, adjusting for clinical and demographic confounders using multivariable statistical models. Methods This retrospective single-center study included adults with multiple sclerosis who underwent autologous HSCT in the Centro de Hematología y Medicina Interna (Clínica Ruiz, Puebla, México) between 2018 and 2025. Participants were stratified into three groups according to cannabis exposure: (1) active users during HSCT, (2) former users, and (3) an age, sex, body mass index (BMI) and EDSS score matched group of non-users. CD34⁺ cell yields were compared across the three groups using non-parametric methods and multivariable linear regression models adjusting for age, sex, BMI, and MS subtype. Early hematologic recovery was assessed in former users and non-users by recording, for each lineage, whether patients achieved at least the lower limit of the institutional reference range and the number of days from aHSCT to recovery. EDSS scores were collected at baseline and at 3, 6, and 12 months after HSCT; multivariable logistic regression was performed to evaluate predictors of EDSS worsening. Results A total of 184 patients were analyzed (16 active users, 76 former users and 92 never users). Significant differences in CD34⁺ counts among the three groups were observed, driven by higher CD34⁺ mobilization in former users compared with non-users (p = 0.048), while active users did not differ significantly from either group. In multivariable linear regression adjusting for age, sex, BMI, and MS subtype, prior cannabis exposure maintained a consistent positive trend with CD34⁺ mobilization (beta = 0.28, p = 0.097). In former users (n = 76) and non-users (n = 92), leukocyte, neutrophil, lymphocyte and platelet recovery was generally similar, although leukocyte recovery occurred slightly earlier and in a higher proportion of former users. Baseline and follow-up median EDSS values did not differ significantly between groups, but EDSS worsening was less frequent in former users, particularly at 6 months (4.4% versus 18.6%; p = 0.015). Multivariable logistic regression confirmed that prior cannabis exposure remained an independent protective factor against short-term EDSS worsening at 6 months (adjusted OR = 0.21, 95% CI 0.05–0.84; p = 0.027), independent of baseline EDSS score, age, sex, BMI, and MS phenotype. Conclusions In this MS cohort undergoing autologous HSCT, a history of cannabis use was associated with higher CD34⁺ progenitor cell mobilization and was not linked to delayed hematologic recovery nor worsening of neurological disability. Multivariable analyses confirm that prior cannabis exposure independently predicts lower risk of short-term neurological deterioration post-aHSCT. Active cannabis use during HSCT did not confer additional mobilization benefit. Larger prospective studies are needed to confirm these findings and to clarify the biological mechanisms linking cannabis exposure with hematopoietic and neurological outcomes.</p>