Hematopoietic Stem Cell Transplantation in ARPC1B Deficiency

Area of Science:

• Immunology
• Genetics
• Hematology

Background:

• ARPC1B gene mutations cause a novel inborn error of immunity with combined immunodeficiency, allergies, autoinflammation, and platelet issues.
• Limited data exists on managing this rare condition and its outcomes.
• This is the first case series evaluating allogeneic hematopoietic stem cell transplant (allo-HSCT) for ARPC1B deficiency.

Purpose of the Study:

• To report the outcomes of the first pediatric cohort treated with allo-HSCT for ARPC1B deficiency.
• To assess the safety and efficacy of allo-HSCT in managing this complex immune disorder.

Main Methods:

• Retrospective analysis of 7 children with homozygous ARPC1B mutations undergoing myeloablative allo-HSCT.
• Evaluation of engraftment, graft-versus-host disease (GvHD), transplant-related complications, and overall survival.
• Follow-up included clinical assessment and monitoring for disease recurrence or complications.

Main Results:

• All patients achieved engraftment; 6/7 had full donor chimerism.
• Most patients experienced manageable GvHD (acute and chronic). One patient developed JC virus-related progressive multifocal leukoencephalopathy, successfully treated with T-cell therapy.
• Six of seven patients are alive and disease-free at a median follow-up of 19 months, with one fatal outcome due to sepsis.

Conclusions:

• Allo-HSCT is a viable and potentially life-saving treatment for ARPC1B-related immunodeficiency.
• The study demonstrates a high survival rate and manageable transplant-related morbidity, supporting allo-HSCT as a therapeutic option.
• Early diagnosis and prompt allo-HSCT are crucial for favorable outcomes in this severe genetic disorder.