Hematopoietic cell transplantation for leukocyte adhesion deficiency: prevention of graft-versus-host-disease.

Introduction: Leukocyte adhesion deficiency (LAD) is a rare genetic disorder that impairs leukocyte migration, leading to severe immune dysfunction and recurrent infections. Although allogeneic hematopoietic cell transplantation (HCT) remains the primary curative treatment for severe LAD, it is complicated by a high incidence of graft-versus-host-disease (GVHD).

Areas covered: This narrative review outlines the key factors influencing GVHD development in patients with LAD-I, the most common LAD subtype, undergoing HCT. It explores established and emerging strategies for preventing GVHD, focusing on their effectiveness and outcomes. The literature search was conducted using PubMed to identify studies reporting HCT for LAD published 1989-2025.

Expert opinion: Conventional GVHD prophylaxis regimens, primarily involving calcineurin inhibitors, have proven insufficient in preventing GVHD in high-risk populations. Among patients undergoing haploidentical HCT, post-transplantation cyclophosphamide has shown efficacy in preventing GVHD, although these results were based on limited cases. Graft manipulation techniques such as CD34⁺ selection have also been explored. However, these approaches are often associated with high graft failure rate and poor survival. Alemtuzumab, which is used in conditioning regimens, has shown promise in lowering GVHD incidence. Further studies are essential to optimize GVHD prophylaxis and improve survival outcomes in patients with LAD undergoing HCT.