Successful Treatment of POLD1 Deficiency With HSCT: Report of Two Years' Experience

POLD1 defect with immunodeficiency is characterized by T-cell and NK-cell lymphopenia, with the patients having a higher susceptibility to herpetic and viral respiratory tract infections. Patients considered for HSCT may be at increased risk of regimen-related toxicity due to impaired DNA repair. Here, we describe the first case of successful HSCT in a patient with POLD1 deficiency who presented at a relatively older age for immunodeficiency and underwent HSCT despite concerns about DNA-related toxicity from the conditioning regimen.

We report the first successful HSCT in an 18-year-old woman with POLD1 deficiency who had recurrent pulmonary infections and shingles, and who was IgRT-dependent. The decision was made to perform HSCT from her matched related donor after informing the family that there was a concern about DNA-related toxicity following the HSCT procedure.

She underwent HSCT from a matched related donor using a reduced-intensity regimen (cyclophosphamide, fludarabine, ATG) with bone marrow and peripheral blood as stem cell sources. GVHD prophylaxis included tacrolimus and low-dose methotrexate. Engraftment occurred promptly, without major complications. Post-HSCT follow-up demonstrated improved T-cell counts and function, and the patient remained well without IgRT.

This first report of HSCT in POLD1 deficiency shows that reduced-intensity conditioning can achieve engraftment with minimal toxicity, supporting HSCT as a feasible option for these patients. The success of HSCT will be understood more clearly as the cases are presented.