Hematopoietic stem cell transplantation for purine nucleoside phosphorylase deficiency: an EBMT-IEWP retrospective study
Abstract
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.
Article Details
Authors (39)
Uli S. Herrmann
1Department of Stem Cell Transplantation, University Children's Hospital, Zurich, Switzerland
Matthias Felber
1Department of Stem Cell Transplantation, University Children's Hospital, Zurich, Switzerland
Austen Worth
4Department of Immunology and Gene Therapy, Great Ormond Street Hospital, London, United Kingdom
Sule Haskologlu
5Department of Pediatric Immunology and Allergy, Ankara University Medical School, Ankara, Turkey
Figen Dogu
5Department of Pediatric Immunology and Allergy, Ankara University Medical School, Ankara, Turkey
Victor A. Lewis
25Department of Pediatric Oncology and Transplant, Alberta Children’s Hospital, University of Calgary, Calgary, AB, Canada
Brigitte Strahm
7Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Children’s Hospital, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Andreas Groll
Andrew R. Gennery
Newcastle University
Fabian Hauck
10Department of Pediatric Hematology and Oncology, Dr. von Hauner Children’s University Hospital, Ludwig Maximilian University, Munich, Germany
Robert Wynn
11Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester, United Kingdom
Mary Coussons
11Department of Blood and Marrow Transplant, Royal Manchester Children's Hospital, Manchester, United Kingdom
Isabelle Meyts
Caroline Lindemans
14Pediatric Blood and Marrow Transplantation Program, Princess Máxima Centre for Pediatric Oncology, Utrecht, The Netherlands
Victoria Bordon
16Department of Pediatric Hemato-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium
Robbert G. M. Bredius
17Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
Jörn-Sven Kühl
18Department of Pediatric Hematology/Oncology/Hemostaseology, Leipzig University Hospital, Leipzig, Germany
Mirjam Völler
19Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Felix Zirngibl
Irina Zaidman
21Department of Pediatric Hematology Oncology, Hadassah Medical Center, Jerusalem, Israel
Alexandra Laberko
22Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Ulrike Zeilhofer
1Department of Stem Cell Transplantation, University Children's Hospital, Zurich, Switzerland
Mathias Hauri-Hohl
1Department of Stem Cell Transplantation, University Children's Hospital, Zurich, Switzerland
Arjan Lankester
23Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands
Aydan Ikinciogullari
5Department of Pediatric Immunology and Allergy, Ankara University Medical School, Ankara, Turkey
Gregory M. T. Guilcher
6Department of Pediatric Oncology and Blood and Marrow Transplant, Alberta Children’s Hospital, University of Calgary Cumming School of Medicine, Calgary, Canada
Annette Hackenberg
Akif Yeşilipek
4Pediatric Stem Cell Transplantation Unit, Antalya Medical Park Hospital, Antalya, Turkey
Graham Davies
4Department of Immunology and Gene Therapy, Great Ormond Street Hospital, London, United Kingdom
Kanchan Rao
26Department of Blood and Bone Marrow Transplantation, Great Ormond Street Hospital, London, United Kingdom
Michael Steven Hershfield
27Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, NC
Suhag H. Parikh
28Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
Patrick Gilbert
30European Society of Blood and Marrow Transplantation, Leiden Study Unit, Leiden, The Netherlands
Claudia Bettoni da Cunha Riehm
31Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany
Michael H. Albert
10Department of Pediatric Hematology and Oncology, Dr. von Hauner Children’s University Hospital, Ludwig Maximilian University, Munich, Germany
Ansgar S. Schulz
32Department of Pediatrics, University Medical Center Ulm, Ulm, Germany
Manfred Hönig
32Department of Pediatrics, University Medical Center Ulm, Ulm, Germany
Bénédicte Neven
Tayfun Güngör
12Department of Hematology/Oncology/Immunology, Gene Therapy, and Stem Cell Transplantation, Eleonore Foundation and Children’s Research Center, University Children’s Hospital, Zürich, Switzerland