ArticleFrontiers in immunology2026
A stepwise institutional approach to refractory autoimmune cytopenia after allogeneic stem cell transplantation in children: a retrospective case series.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Refractory autoimmune cytopenia (AIC) after allogeneic hematopoietic stem cell transplantation carries substantial morbidity and mortality in children. Conventional therapy fails in approximately half of patients, and escalating immunosuppression produces cumulative toxicity yet rarely durable remission. We hypothesised that refractory AIC reflects failed immune reconstitution driven by pharmacologic immunosuppression impairing regulatory T-cell (Treg) development, and that withdrawing immunosuppression might permit endogenous tolerance recovery. Methods: We reviewed 20 consecutive children with refractory AIC after allo-HSCT (2019-2025). All received corticosteroids (± IVIG) and rituximab. Non-responders underwent withdrawal of all immunosuppressants, including calcineurin inhibitors (Step 1, n=5). Those who failed Step 1 or presented with life-threatening deterioration were allocated to parallel second-line strategies based on cryopreserved donor cell availability: PD-1 inhibitors ± interferon-alpha2b (Step 2, n=8) or donor lymphocyte infusion (Step 3, n=7). The primary endpoint was sustained remission; the secondary endpoint was optimal outcome (sustained remission without relapse and without Grade II-IV graft-versus-host disease [GVHD]). Results: All 20 children achieved sustained remission (100%; 95% CI 83.2-100%) at a median follow-up of 22.2 months. Optimal outcomes occurred in 80% of Step 1 patients versus 62.5% in Step 2 and 28.6% in Step 3 (Cochran-Armitage trend test, P = 0.070). GVHD incidence increased with treatment intensity: 20% after Step 1, 50% after Step 2, and 100% after Step 3 (P<0.001); all events were acute and self-limited. Conclusion: All children achieved sustained remission with this stepwise protocol, and the most favourable outcomes occurred in the group that withdrew immunosuppressants alone. Because treatment was not randomised, this apparent advantage may reflect patient selection rather than true efficacy. These observations are exploratory and require prospective validation.
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