Unrelated bone marrow transplantation for chronic granulomatous disease using a targeted busulfan combination conditioning regimen

Abstract

A 7-month-old male infant, who suffered from systemic infection following BCG vaccination, was diagnosed as having p67^phox-deficient chronic granulomatous disease. At the age of three, he underwent bone marrow transplantation from an HLA-8/8-matched unrelated donor following a conditioning regimen that consisted of intravenous busulfan, fludarabine, and rabbit anti-thymocyte globulin. A total of 18.8 mg of Bu per kg body weight was administered, which was closely adjusted to obtain the recommended total cumulative area under the curve (65–70 mg/L×hr). Hematological engraftment was prompt, and serial chimerism analyses showed sustained complete chimerism on and after day 69. The patient was alive and free from disease 1 year and 9 months after transplantation with no severe treatment-related toxicity. This conditioning regimen is feasible for hematopoietic stem cell transplantation against nonmalignant diseases with a high risk of graft rejection, although long-term follow-up will be required to check for late adverse effects, such as gonadal dysfunction.