A minimal dose of unmanipulated bone marrow infusion without conditioning for T-B+NK- severe combined immunodeficiency

Abstract

Hematopoietic stem cell transplantation (HSCT) is the standard method of reconstituting immune function in severe combined immunodeficiency (SCID); however, there is no consensus about optimal cell doses. In this study, we investigated HSCT outcomes and immune reconstitution, following minimal dose (MD) HSCT in T cell-negative (T-), B cell-positive (B+), natural killer cell-negative (NK-) SCID patients. We retrospectively reviewed patients with SCID who received HSCT between 2002–2018. Standard dose (SD) and MD were classified based on a total nucleated cell count (TNC) of 1.0 × 108/kg or more and less. Total seven patients with SCID received HSCT. MD group (n = 4) were administered 5 mL or less of bone marrow without conditioning, with median TNC and CD34+ cell counts of 0.49 × 108/kg and 0.62 × 106/kg, respectively. T cells recovered within a year, and immunoglobulin supplementation was discontinued at median 3.5 months after HSCT in all MD recipients. All MD recipients were alive without disease recurrence at a median of 126.9 months after HSCT, exhibiting donor chimerism in the range of 10.1–100%. In patients with T-B + NK- SCID, sufficient therapeutic effects were safely obtained with minimal dose of bone marrow infusion without conditioning.