Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey

Alice Y Chan¹, Jennifer W Leiding², Xuerong Liu³, Brent R Logan³, Lauri M Burroughs⁴, Eric J Allenspach⁵, Suzanne Skoda-Smith⁵, Gulbu Uzel⁶, Luigi D Notarangelo⁶, Mary Slatter⁷, Andrew R Gennery⁷, Angela R Smith⁸, Sung-Yun Pai^{9

10

11}, Michael B Jordan¹², Rebecca A Marsh¹², Morton J Cowan¹, Christopher C Dvorak¹, John A Craddock¹³, Susan E Prockop¹⁴, Shanmuganathan Chandrakasan¹⁵, Neena Kapoor¹⁶, Rebecca H Buckley¹⁷, Suhag Parikh¹⁷, Deepak Chellapandian¹⁸, Benjamin R Oshrine¹⁸, Jeffrey J Bednarski¹⁹, Megan A Cooper¹⁹, Shalini Shenoy¹⁹, Blachy J Davila Saldana²⁰, Lisa R Forbes²¹, Caridad Martinez²², Elie Haddad²³, David C Shyr²⁴, Karin Chen²⁴, Kathleen E Sullivan²⁵, Jennifer Heimall²⁵, Nicola Wright²⁶, Monica Bhatia²⁷, Geoffrey D E Cuvelier²⁸, Frederick D Goldman²⁹, Isabelle Meyts^{30

31}, Holly K Miller³², Markus G Seidel³³, Mark T Vander Lugt³⁴, Rosa Bacchetta³⁵, Katja G Weinacht³⁵, Jeffrey R Andolina³⁶, Emi Caywood³⁷, Hey Chong³⁸, Maria Teresa de la Morena⁵, Victor M Aquino³⁹, Evan Shereck⁴⁰, Jolan E Walter^{41

42

43}, Morna J Dorsey¹, Christine M Seroogy⁴⁴, Linda M Griffith⁴⁵, Donald B Kohn⁴⁶, Jennifer M Puck¹, Michael A Pulsipher¹⁶, Troy R Torgerson⁴⁷

Affiliations

¹ Division of Pediatric Allergy, Immunology, BMT, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA, United States.
² Department of Pediatrics, Johns Hopkins All Children's Hospital, University of South Florida, St. Petersburg, FL, United States.
³ Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, United States.
⁴ Department of Pediatrics, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, United States.
⁵ Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, United States.
⁶ Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
⁷ Primary Immunodeficiency Group, Paediatric Immunology and Haematopoietic Stem Cell Transplantation, Translational and Clinical Research Institute, Great North Childrens' Hospital, Newcastle University, Newcastle upon Tyne, United Kingdom.
⁸ Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, MN, United States.
⁹ Division of Pediatric Hematology-Oncology, Boston Children's Hospital, Boston, MA, United States.
¹⁰ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.
¹¹ Department of Pediatrics, Harvard Medical School, Boston, MA, United States.
¹² Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, United States.
¹³ Texas Children's Cancer Center, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United States.
¹⁴ Stem Cell Transplant and Cellular Therapy Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
¹⁵ Division of Bone Marrow Transplant, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, United States.
¹⁶ Section of Transplantation and Cellular Therapy, Cancer and Blood Disease Institute, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, United States.
¹⁷ Departments of Pediatrics and Immunology, Duke University School of Medicine, Durham, NC, United States.
¹⁸ Cancer and Blood Disorders Institute, Blood and Marrow Transplant Program, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States.
¹⁹ Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States.
²⁰ Division of Blood and Marrow Transplantation, Children's National Health System, George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
²¹ Department of Pediatrics, Immunology, Allergy, and Retrovirology Baylor College of Medicine, Texas Children's Hospital William T. Shearer Center for Human Immunobiology, Houston, TX, United States.
²² Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital Cancer Center, Houston, TX, United States.
²³ Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
²⁴ Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, United States.
²⁵ Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, United States.
²⁶ Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
²⁷ Pediatric Stem Cell Transplantation, Columbia University College of Physicians and Surgeons, New York, NY, United States.
²⁸ Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.
²⁹ Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States.
³⁰ Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium.
³¹ Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
³² Phoenix Children's Hospital, Phoenix, AZ, United States.
³³ Research Unit for Pediatric Hematology and Immunology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.
³⁴ Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States.
³⁵ Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, United States.
³⁶ Department of Pediatrics, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, NY, United States.
³⁷ Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, United States.
³⁸ UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States.
³⁹ Department of Pediatrics, University of Texas Southwestern Medical Center Dallas, Dallas, TX, United States.
⁴⁰ Department of Pediatrics, Oregon Health & Science University, Portland, OR, United States.
⁴¹ Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, St. Petersburg, FL, United States.
⁴² Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States.
⁴³ Division of Allergy and Immunology, Department of Pediatrics, Massachusetts General Hospital for Children, Boston, MA, United States.
⁴⁴ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.
⁴⁵ Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
⁴⁶ Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, CA, United States.
⁴⁷ Allen Institute for Immunology and Department of Pediatrics, University of Washington, Seattle, WA, United States.

PMID: 32153572
PMCID: PMC7046837
DOI: 10.3389/fimmu.2020.00239

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey

Alice Y Chan et al. Front Immunol. 2020.

. 2020 Feb 21:11:239.

doi: 10.3389/fimmu.2020.00239. eCollection 2020.

Authors

Affiliations

¹ Division of Pediatric Allergy, Immunology, BMT, Benioff Children's Hospital, University of California, San Francisco, San Francisco, CA, United States.
² Department of Pediatrics, Johns Hopkins All Children's Hospital, University of South Florida, St. Petersburg, FL, United States.
³ Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, United States.
⁴ Department of Pediatrics, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, United States.
⁵ Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA, United States.
⁶ Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
⁷ Primary Immunodeficiency Group, Paediatric Immunology and Haematopoietic Stem Cell Transplantation, Translational and Clinical Research Institute, Great North Childrens' Hospital, Newcastle University, Newcastle upon Tyne, United Kingdom.
⁸ Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, MN, United States.
⁹ Division of Pediatric Hematology-Oncology, Boston Children's Hospital, Boston, MA, United States.
¹⁰ Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, United States.
¹¹ Department of Pediatrics, Harvard Medical School, Boston, MA, United States.
¹² Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, United States.
¹³ Texas Children's Cancer Center, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United States.
¹⁴ Stem Cell Transplant and Cellular Therapy Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
¹⁵ Division of Bone Marrow Transplant, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, United States.
¹⁶ Section of Transplantation and Cellular Therapy, Cancer and Blood Disease Institute, Keck School of Medicine, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, United States.
¹⁷ Departments of Pediatrics and Immunology, Duke University School of Medicine, Durham, NC, United States.
¹⁸ Cancer and Blood Disorders Institute, Blood and Marrow Transplant Program, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States.
¹⁹ Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States.
²⁰ Division of Blood and Marrow Transplantation, Children's National Health System, George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
²¹ Department of Pediatrics, Immunology, Allergy, and Retrovirology Baylor College of Medicine, Texas Children's Hospital William T. Shearer Center for Human Immunobiology, Houston, TX, United States.
²² Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital Cancer Center, Houston, TX, United States.
²³ Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
²⁴ Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, United States.
²⁵ Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, United States.
²⁶ Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada.
²⁷ Pediatric Stem Cell Transplantation, Columbia University College of Physicians and Surgeons, New York, NY, United States.
²⁸ Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.
²⁹ Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, United States.
³⁰ Laboratory of Inborn Errors of Immunity, Department of Immunology, Microbiology and Transplantation, KU Leuven, Leuven, Belgium.
³¹ Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
³² Phoenix Children's Hospital, Phoenix, AZ, United States.
³³ Research Unit for Pediatric Hematology and Immunology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria.
³⁴ Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States.
³⁵ Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, United States.
³⁶ Department of Pediatrics, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, NY, United States.
³⁷ Nemours/Alfred I duPont Hospital for Children, Wilmington, DE, United States.
³⁸ UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States.
³⁹ Department of Pediatrics, University of Texas Southwestern Medical Center Dallas, Dallas, TX, United States.
⁴⁰ Department of Pediatrics, Oregon Health & Science University, Portland, OR, United States.
⁴¹ Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, St. Petersburg, FL, United States.
⁴² Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins All Children's Hospital, St. Petersburg, FL, United States.
⁴³ Division of Allergy and Immunology, Department of Pediatrics, Massachusetts General Hospital for Children, Boston, MA, United States.
⁴⁴ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.
⁴⁵ Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
⁴⁶ Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, CA, United States.
⁴⁷ Allen Institute for Immunology and Department of Pediatrics, University of Washington, Seattle, WA, United States.

PMID: 32153572
PMCID: PMC7046837
DOI: 10.3389/fimmu.2020.00239

Abstract

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.

Keywords: autoimmunity; genetics; hematopoietic cell transplant; immune dysregulation; primary immune deficiencies.

Copyright © 2020 Chan, Leiding, Liu, Logan, Burroughs, Allenspach, Skoda-Smith, Uzel, Notarangelo, Slatter, Gennery, Smith, Pai, Jordan, Marsh, Cowan, Dvorak, Craddock, Prockop, Chandrakasan, Kapoor, Buckley, Parikh, Chellapandian, Oshrine, Bednarski, Cooper, Shenoy, Davila Saldana, Forbes, Martinez, Haddad, Shyr, Chen, Sullivan, Heimall, Wright, Bhatia, Cuvelier, Goldman, Meyts, Miller, Seidel, Vander Lugt, Bacchetta, Weinacht, Andolina, Caywood, Chong, de la Morena, Aquino, Shereck, Walter, Dorsey, Seroogy, Griffith, Kohn, Puck, Pulsipher and Torgerson.

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Figures

**Figure 1**
Clinical Manifestations of PIRD Patients. **(A)** PIRD patients have a range of clinical manifestations. Hatched bars represent the type of immune dysregulation [i.e., overactive immune features (autoimmunity, autoinflammation, lymphoproliferation) or underactive immune features (immunodeficiency)] and solid bars represent organ involvement. **(B)** Heat map of the clinical manifestations (rows) in the disease groups (columns). Color indicates the percentage of patients within that disease group that have the particular clinical manifestation. Right bar represents the color scaling. APDS, activated PI3K delta syndrome; CID, combined immunodeficiency; CVID, common variable immunodeficiency; IBD, inflammatory bowel disease; Innate, disorders of innate immunity; LPD, lymphoproliferative disorder; NFKB, nuclear factor kappa-light-chain-enhancer of activated B cells disorders; Tregopathies, T regulatory cell disorders.

**Figure 2**
HCT Outcomes in patients with PIRD. **(A)** Bar graph illustrating the resolution of disease at any point post-HCT in each of the disease groups based on percentages within the group. Numbers represent patients in each subgroup. **(B)** Kaplan-Meier estimate of survival in PIRD patients undergoing HCT. Dotted lines represent 95% confidence interval.

See this image and copyright information in PMC

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Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey

Affiliations

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey

Authors

Affiliations

Abstract

Figures

References

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MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources