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

• HCT with HLA-matched and -mismatched donors can yield satisfactory long-term clinical and neurological outcomes in PNP-deficient patients.

• Early diagnose is difficult but crucial for improving OS which was best in early diagnosed patients without neurological symptoms.

Purine nucleoside phosphorylase (PNP) deficiency causes inadequate purine metabolite detoxification, leading to combined immunodeficiency and variable neurological symptoms. Hematopoietic stem cell transplantation (HCT) cures the immunodeficiency, but large studies on long-term outcomes are lacking. In a retrospective EBMT study, we investigated 46 patients with PNP deficiency from 21 centers. We analyzed the presenting clinical signs and outcomes after HCT. Cognition (0-3), hearing (0-3), interaction (0-4), movement (0-4) and occupation (0-3) (CHIMO-score) were scored at 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, with 41% of cases involving infectious, 39% neurological, 15% infectious/neurological, and 5% autoimmune symptoms. At timepoint of HCT (median age: 26 (2-192) mo.), 88% of patients exhibited neurologic abnormalities. 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) probability of 86% (CI 77-97%)/75% (CI 64-89%), respectively. At FU, high-level donor chimerism (>50-100%) was observed in 85% of patients, and low-level (11-50%) in 15% of patients resulting in resolution of T lymphopenia. The median scores for cognition, hearing, interaction, movement, and occupation were 3 (0-3), 3 (1-3), 4 (1-4), 3 (1-4), and 2 (0-3), respectively, with a median CHIMO-score of 14 (6-17). Patients who underwent HCT <24 months after initial presentation demonstrated superior OS (p=0.049). Neurological symptoms occurring <11 months of age were associated with reduced OS (p=0.027). While the overall results were satisfactory, earlier diagnosis could further improve outcomes.