Haomin Yan, Dongjun Li, Xiaoxi Lu, Xue Yang, Yiping Zhu, Shuwen Sun
Pyruvate kinase deficiency (PKD) is a rare autosomal recessive inherited hemolytic anemia caused by pathogenic variants in the PKLR gene. The disease exhibits marked clinical heterogeneity, ranging from compensated anemia to severe transfusion-dependent phenotypes presenting early in childhood. Although supportive care and emerging pharmacologic agents such as pyruvate kinase activators have improved disease management, treatment options remain limited for patients with severe, transfusion-dependent disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potential curative approach. However, clinical experience in pediatric PKD remains limited, and reported outcomes are heterogeneous. In particular, data regarding standardized conditioning strategies, donor variability, and early post-transplant outcomes are still insufficient. Here, we report a single-center case series of six pediatric patients with genetically confirmed PKD who underwent allo-HSCT between 2019 and 2026. The cohort included both matched sibling and unrelated donors with varying HLA compatibility. All patients achieved successful hematopoietic engraftment, with neutrophil and platelet recovery occurring within 12-16 days post-transplantation. Complete donor chimerism (>98%) was achieved in all evaluable patients by day +21. No primary graft failure was observed, and no severe acute or chronic graft-versus-host disease occurred during early follow-up. Importantly, patients demonstrated rapid correction of transfusion dependence following transplantation. However, follow-up duration was heterogeneous, ranging from several months to over six years, and long-term outcomes remain under continued observation. This study provides a homogeneous real-world experience suggesting that allo-HSCT using a thiotepa- and ATG-containing myeloablative regimen is feasible in selected pediatric PKD patients, including those receiving unrelated donor grafts. These findings support further investigation of standardized transplant approaches and early intervention strategies in severe pediatric PKD. Larger multicenter studies with long-term follow-up are required to validate safety, durability, and late effects of transplantation in this rare disease.