The research on the treatment of primary immunodeficiency diseases by hematopoietic stem cell transplantation: A bibliometric analysis from 2013 to 2022

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TL;DR

This bibliometric analysis of 602 publications from 2013 to 2022 maps the research landscape of hematopoietic stem cell transplantation (HSCT) for primary immunodeficiency diseases (PID). The United States leads in productivity, and recent research trends include gene therapy, gene editing, and inborn errors of immunity. The findings highlight HSCT as an established curative treatment, with survival rates reaching 90% for some PIDs, and identify emerging frontiers in CRISPR/Cas-based gene editing approaches.

Full summary

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**Background:** Primary immunodeficiency diseases (PID) are a group of inherited disorders characterized by hypofunction or absence of parts of the immune system, predisposing patients to infections, malignancy, inflammation, and autoimmunity. Approximately 500 different types have been genetically identified. Hematopoietic stem cell transplantation (HSCT) has been a definitive treatment since the first successful allogeneic transplant in 1968 for a 5-month-old male with lymphopenic immunological deficiency. Despite the growing body of literature, no prior study had provided a comprehensive bibliometric summary of HSCT for PID. This study aimed to use bibliometric and visualization analysis to track research hotspots and frontier trends in this field from 2013 to 2022.

**Methods:** In October 2022, a literature search was performed using the Web of Science Core Collection (WoSCC). The search terms were Topic = "(hematopoietic stem cell transplantation) or (Bone Marrow Transplantation)" AND "(primary immunodeficiency diseases) or (inborn errors of immunity)." The search covered January 2013 to October 2022, limited to English-language documents including articles, reviews, proceedings, editorial materials, and letters. A total of 602 documents were identified. Bibliometric analysis was conducted using CiteSpace 6.1.R3 (64-bit) and VOSviewer (Version 1.6.18) to analyze co-cited publications, countries, institutions, journals, authors, keywords, and keyword burst networks.

**Key Results:** The 602 documents included 414 articles, 167 review articles, 9 meeting abstracts, 6 early access, 5 editorial materials, 5 letters, 4 proceedings papers, 3 book chapters, and 1 reprint. The top 5 most productive authors were Gennery, Andrew R. (40 publications), Slatter, Mary A. (26 publications), Torgerson, Troy R. (18 publications), Notarangelo, Luigi D. (17 publications), and Neven, Benedicte (17 publications). The top 5 cited authors were Gennery, Andrew R. (463 citations), Kohn DB (212 citations), Veys, Paul (217 citations), Neven, Benedicte (192 citations), and Chiesa, Robert (172 citations). A total of 80 countries/regions were identified; the top 5 productive countries were the United States (229 documents, 7210 citations), England (99 documents, 2599 citations), Germany (84 documents, 2202 citations), Netherlands (34 documents, 1261 citations), and Turkey (45 documents, 1025 citations). The top 5 productive institutions were the National Institute of Allergy and Infectious Diseases (37 documents, 1007 citations), Newcastle University (36 documents, 750 citations), Duke University (16 documents, 666 citations), Boston Children's Hospital (16 documents, 598 citations), and University of Washington (17 documents, 551 citations). The European Society for Blood and Marrow Transplantation was the most important society, with 19 documents. Among 149 journals, 12 published over 10 documents, accounting for 296 documents (49.2% of total literature). The top 5 productive journals were Journal of Clinical Immunology (65 documents, 795 citations), Frontiers in Immunology (60 documents, 678 citations), Journal of Allergy and Clinical Immunology (38 documents, 1990 citations), Frontiers in Pediatrics (24 documents, 283 citations), and Blood (20 documents, 591 citations). Six Highly Cited Papers were identified, including "Transplantation Outcomes for Severe Combined Immunodeficiency, 2000–2009" (407 citations) and "Update on the use of immunoglobulin in human disease: A review of evidence" (296 citations). The top 10 keywords included bone-marrow-transplantation (146 occurrences), primary immunodeficiency (144), stem-cell transplantation (139), chronic granulomatous-disease (100), hematopoietic stem cell transplantation (108), children (115), severe combined immunodeficiency (98), mutations (86), deficiency (71), and disease (71). Recent research trends from 2019 to 2022 included "inborn errors of immunity," "gene editing," and "enteropathy."

**Clinical Implications:** This bibliometric analysis confirms that HSCT is an established curative treatment for many PIDs, with survival and cure rates reaching 90% for some specific diseases. The increasing number of publications since 2016 reflects advances in genetic diagnoses, reduced toxicity conditioning, increased use of alternative donors, and new graft engineering approaches. The emergence of gene therapy and CRISPR/Cas-based gene editing as recent research frontiers is particularly significant, as gene therapy using autologous HSCs can avoid limitations of allogeneic HSCT such as immunologic complications and donor availability. However, challenges remain, including the risk of insertional mutagenesis with gene addition approaches and unintended genetic alterations with CRISPR/Cas systems. The study provides a roadmap for researchers to understand key contributors, institutions, journals, and evolving research priorities in this field.