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.

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Journal
Blood
Published
2025-09-22
DOI
https://doi.org/10.1182/blood.2025029640
Citations
1
Primary Topic
Cytomegalovirus and herpesvirus research
Type
article
Field-Weighted Citation Impact
1.35

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article

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

Suhag H Parikh, Mathias Hauri‐Hohl, Alexandra Laberko, Bénédicte Neven et al.
1 citations
Blood
Cytomegalovirus and herpesvirus research
1.35
article

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

Suhag H Parikh, Mathias Hauri‐Hohl, Alexandra Laberko, Bénédicte Neven, Matthias Felber, Aydan İkincioğulları, Michael S. Hershfield, Andrew Richard Gennery, Mary Coussons, Ansgar Schulz, Fabian Hauck, Robbert G. M. Bredius, Joachim Kühl, Michael H. Albert, Andreas H. Groll, Figen Doğu, Brigitte Strahm, Isabelle Meyts, Zehra Şule Haskoloğlu, M. Akif Yeşilipek, Caroline A. Lindemans, Victor Lewis, Felix Zirngibl, Austen Worth, Annette Hackenberg, U. Herrmann, M. Victoria Bordon Cueto de Braem, Arjan C. Lankester, Robert Wynn, Gregory M.T. Guilcher, Ulrike Zeilhofer, Claudia Bettoni da Cunha Riehm, Irina Zaidman, Patrick Gilbert, Tayfun Güngör, Mirjam Völler, E. Graham Davies, Manfred Hönig
article en
1 citations

Abstract

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.

BloodVol. 147(2)
University of Bern (CH), Hôpital Necker-Enfants Malades (FR), Ankara University (TR), Emory University (US), Inserm (FR), University of Freiburg (DE), Duke University (US), Universität Ulm (DE), Hebrew University of Jerusalem (IL), Hadassah Medical Center (IL), Leiden University Medical Center (NL), Great Ormond Street Hospital (GB), University Hospital of Bern (CH), Ghent University Hospital (BE), University Medical Center Freiburg (DE), Alberta Children's Hospital (CA), University Medical Center Utrecht (NL), Medizinische Hochschule Hannover (DE), Humboldt-Universität zu Berlin (DE), European Society for Blood and Marrow Transplantation (NL), University Hospital Münster (DE), Antalya Eğitim ve Araştırma Hastanesi (TR), University Children’s Hospital Bern (CH), University Hospital Leipzig (DE), Duke Medical Center (US), Princess Máxima Center (NL), Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology (RU), University Children's Hospital Zurich (CH), Children's Healthcare of Atlanta (US), University Hospital Ulm (DE), Royal Manchester Children's Hospital (GB), Antalya IVF (TR), University College London (GB), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE), Ludwig-Maximilians-Universität München (DE), Newcastle University (GB), KU Leuven (BE)
Fonds Wetenschappelijk Onderzoek, Vlaamse regering
Openalex Percentile: Top 15%
Cytomegalovirus and herpesvirus research
1.35
DOIOpen Access PDFOpenAlex
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