Genotype, oxidase status, and preceding infection or autoinflammation do not affect allogeneic HCT outcomes for CGD

Author:

Leiding Jennifer W.12ORCID,Arnold Danielle E.3ORCID,Parikh Suhag4ORCID,Logan Brent5,Marsh Rebecca A.6,Griffith Linda M.7,Wu Ruizhe5,Kidd Sharon8,Mallhi Kanwaldeep9,Chellapandian Deepak10ORCID,Si Lim Stephanie J.11ORCID,Grunebaum Eyal1213,Falcone E. Liana1415,Murguia-Favela Luis16ORCID,Grossman Debbi15,Prasad Vinod K.17ORCID,Heimall Jennifer R.18,Touzot Fabien19ORCID,Burroughs Lauri M.9,Bleesing Jack6,Kapoor Neena20,Dara Jasmeen8,Williams Olatundun2122,Kapadia Malika23,Oshrine Benjamin R.10,Bednarski Jeffrey J.24ORCID,Rayes Ahmad25,Chong Hey26,Cuvelier Geoffrey D. E.27ORCID,Forbes Satter Lisa R.28ORCID,Martinez Caridad29ORCID,Vander Lugt Mark T.30,Yu Lolie C.31,Chandrakasan Shanmuganathan4,Joshi Avni32,Prockop Susan E.2333ORCID,Dávila Saldaña Blachy J.34ORCID,Aquino Victor35,Broglie Larisa A.36ORCID,Ebens Christen L.37ORCID,Madden Lisa M.38,DeSantes Kenneth39,Milner Jordan40ORCID,Rangarajan Hemalatha G.41ORCID,Shah Ami J.42,Gillio Alfred P.43,Knutsen Alan P.44,Miller Holly K.45,Moore Theodore B.46,Graham Pamela15,Bauchat Andrea17,Bunin Nancy J.47,Teira Pierre19,Petrovic Aleksandra9,Chandra Sharat6ORCID,Abdel-Azim Hisham2048,Dorsey Morna J.8ORCID,Birbrayer Olga23,Cowan Morton J.8ORCID,Dvorak Christopher C.8ORCID,Haddad Elie19ORCID,Kohn Donald B.46ORCID,Notarangelo Luigi D.15ORCID,Pai Sung-Yun3,Puck Jennifer M.8ORCID,Pulsipher Michael A.25ORCID,Torgerson Troy R.49ORCID,Malech Harry L.15ORCID,Kang Elizabeth M.15ORCID

Affiliation:

1. 1Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University, Baltimore, MD

2. 2Institute for Clinical and Translational Research, Johns Hopkins All Children’s Hospital, St. Petersburg, FL

3. 3National Cancer Institute, National Institutes of Health, Bethesda, MD

4. 4Aflac Cancer and Blood Disorders Center, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA

5. 5Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI

6. 6Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Cincinnati, OH

7. 7Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

8. 8Pediatric Allergy, Immunology, and Blood and Marrow Transplant Division, UCSF Benioff Children’s Hospital, San Francisco, CA

9. 9Fred Hutchinson Cancer Research Center, Department of Pediatrics, University of Washington, and Seattle Children’s Hospital, Seattle, WA

10. 10Center for Cell and Gene Therapy for Non-Malignant Conditions, Johns Hopkins All Children’s Hospital, St Petersburg, FL

11. 11Department of Pediatrics, John A. Burns School of Medicine, University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, HI

12. 12Division of Immunology and Allergy, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada

13. 13Faculty of Medicine, University of Toronto, Toronto, ON, Canada

14. 14Center for Inflammation, Immunity and Infectious Diseases, Montreal Clinical Research Institute, Montreal, QC, Canada

15. 15Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

16. 16Section of Hematology/Immunology, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada

17. 17Division of Pediatric Transplant and Cellular Therapy, Department of Pediatrics, Duke University Medical Center, Durham, NC

18. 18Division of Allergy and Immunology, Department of Pediatrics, Children’s Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA

19. 19Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, QC, Canada

20. 20Division of Hematology, Oncology and Blood and Marrow Transplant, Children’s Hospital, Los Angeles, CA

21. 21Division of Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL

22. 22Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, Morgan Stanley Children's Hospital, New York-Presbyterian/Columbia University Irving Medical Center, New York, NY

23. 23Division of Hematology-Oncology, Boston Children's Hospital, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA

24. 24Washington University, St. Louis Children’s Hospital, St. Louis, MO

25. 25Division of Pediatric Hematology and Oncology, Intermountain Primary Children’s Hospital, Huntsman Cancer Institute at the University of Utah Spencer Fox Eccles School of Medicine, Salt Lake City, UT

26. 26UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA

27. 27Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada

28. 28Immunology, Allergy and Retrovirology, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX

29. 29Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital Center for Gene and Cell Therapy, Houston, TX

30. 30Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI

31. 31Louisiana State University, Children’s Hospital, New Orleans, LA

32. 32Division of Pediatric Allergy and Immunology, Mayo Clinic, Rochester, MN

33. 33Stem Cell Transplantation and Cellular Therapy, MSK Kids, Memorial Sloan Kettering Cancer Center, New York, NY

34. 34Division of Blood and Marrow Transplantation, Children's National Hospital-George Washington University School of Medicine and Health Sciences, Washington, DC

35. 35Division of Hematology and Oncology, Department of Pediatrics, UT Southwestern Medical Center Dallas, Dallas, TX

36. 36Division of Pediatric Hematology-Oncology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI

37. 37Division of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN

38. 38Pediatric Bone Marrow Transplant Program, Texas Transplant Institute, San Antonio, TX

39. 39American Family Children's Hospital, University of Wisconsin, Madison, WI

40. 40Hematology and Oncology, Maria Fareri Children's Hospital, New York Medical College, Valhalla, NY

41. 41Nationwide Children’s Hospital, Columbus, OH

42. 42Pediatric Stem Cell Transplantation Program and Division of Pediatric Hematology, Oncology, Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford University, Stanford, CA

43. 43Institute for Pediatric Cancer and Blood Disorders, Hackensack University Medical Center, Hackensack, NJ

44. 44Pediatric Allergy and Immunology, Saint Louis University and SSM Health Cardinal Glennon Children's Hospital, St. Louis, MO

45. 45Center for Cancer and Blood Disorders, Phoenix Children's Hospital, and The University of Arizona College of Medicine-Phoenix, Phoenix, AZ

46. 46Department of Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA

47. 47Division of Oncology, Children's Hospital of Philadelphia, and University of Pennsylvania School of Medicine, Philadelphia, PA

48. 48Cancer Center, Children's Hospital and Medical Center, Loma Linda University School of Medicine, Loma Linda, CA

49. 49Allen Institute for Immunology, Seattle, WA

Abstract

Abstract Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening infections and inflammatory conditions. Hematopoietic cell transplantation (HCT) is the definitive treatment for CGD, but questions remain regarding patient selection and impact of active disease on transplant outcomes. We performed a multi-institutional retrospective and prospective study of 391 patients with CGD treated either conventionally (non-HCT) enrolled from 2004 to 2018 or with HCT from 1996 to 2018. Median follow-up after HCT was 3.7 years with a 3-year overall survival of 82% and event-free survival of 69%. In a multivariate analysis, a Lansky/Karnofsky score <90 and use of HLA-mismatched donors negatively affected survival. Age, genotype, and oxidase status did not affect outcomes. Before HCT, patients had higher infection density, higher frequency of noninfectious lung and liver diseases, and more steroid use than conventionally treated patients; however, these issues did not adversely affect HCT survival. Presence of pre-HCT inflammatory conditions was associated with chronic graft-versus-host disease. Graft failure or receipt of a second HCT occurred in 17.6% of the patients and was associated with melphalan-based conditioning and/or early mixed chimerism. At 3 to 5 years after HCT, patients had improved growth and nutrition, resolved infections and inflammatory disease, and lower rates of antimicrobial prophylaxis or corticosteroid use compared with both their baseline and those of conventionally treated patients. HCT leads to durable resolution of CGD symptoms and lowers the burden of the disease. Patients with active infection or inflammation are candidates for transplants; HCT should be considered before the development of comorbidities that could affect performance status. This trial was registered at www.clinicaltrials.gov as #NCT02082353.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Cited by 9 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3