Hematopoietic stem cell transplantation for purine nucleoside phosphorylase deficiency: an EBMT-IEWP retrospective study

Purine nucleoside phosphorylase (PNP) deficiency causes inadequate purine metabolite detoxification, which leads to combined immunodeficiency and variable neurologic symptoms. Hematopoietic stem cell transplantation (HSCT) cures the immunodeficiency, but large studies on the long-term outcomes are lacking. In a retrospective study of the European Society for Blood and Marrow Transplantation, we investigated 46 patients with PNP deficiency from 21 centers. We analyzed the presenting clinical signs and outcomes after HSCT. Cognition (0-3), hearing (0-3), interaction (0-4), movement (0-4), and occupation (0-3) (CHIMO) were scored at the last follow-up (FU) visit (no impairment, 17; mild, 15-16; moderate, 12-14; and severe impairment, <12). The median age at initial presentation was 7.5 (1-48) months. The patients presented with infections (41%), neurological dysfunction (39%), both (15%), or autoimmune disease (5%). At the time of HSCT (median age, 26 [2-192] months), neurological abnormalities were observed in 88% of patients. After a median FU of 7.9 (1.0-22.3) years, 40 patients were alive with a 3-year overall survival (OS)/event-free survival (EFS) probabilities of 86% (confidence interval [CI], 77%-97%)/75% (CI, 64%-89%), respectively. High-level (>50%-100%)/low-level donor chimerism (11%-50%) was observed in 85%/15% of patients, respectively, leading to resolution of T lymphopenia. The median overall CHIMO score was 14 (6-17), while the median scores for each component were 3 (0-3), 3 (1-3), 4 (1-4), 3 (1-4), and 2 (0-3), respectively. Patients who underwent HSCT before 24 months after the initial presentation demonstrated superior OS (P = .049). Neurological symptoms that occurred before 11 months of age were associated with reduced OS (P = .027). While the overall results were satisfactory, earlier diagnosis could further improve outcomes.