title: Avascular necrosis of bone after allogeneic hematopoietic cell transplantation in children and adolescents.
abstract: We conducted a nested case-control study within a cohort of 6244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents after allogeneic transplantation. Eligible patients were ≤21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States, and had survived ≥ 6 months from transplantation. Overall, 160 patients with AVN and 478 control subjects matched by year of transplant, length of follow-up and transplant center were identified. Patients and control subjects were confirmed via central review of radiology, pathology, and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (≥5 years), female gender, and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared with patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with nonmalignant diseases and those who had received reduced-intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression after hematopoietic cell transplantation for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication.
authors.affiliation: Banner Children's Specialists Pediatric Hematology/Oncology, Banner Health, Mesa, Arizona.
authors.forename: Xiaxin
authors.initials: X
authors.lastname: Li
authors.affiliation: Division of Biostatistics, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Ruta
authors.initials: R
authors.lastname: Brazauskas
authors.affiliation: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Hematopoietic Stem Cell Transplantation Program, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Amal
authors.initials: A
authors.lastname: Al-Seraihy
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: K Scott
authors.initials: KS
authors.lastname: Baker
authors.affiliation: Clinique Universitaire d'Hematologie, University Hospital, Grenoble, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.affiliation: Pediatric Blood and Marrow Transplant Program, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Haydar A
authors.initials: HA
authors.lastname: Frangoul
authors.affiliation: Bone Marrow & Stem Cell Transplant Program, Oregon Health and Science University, Portland, Oregon.
authors.forename: James L
authors.initials: JL
authors.lastname: Gajewski
authors.affiliation: Division of Hematology and Oncology, All Children's Hospital, St. Petersburg, Florida.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hale
authors.affiliation: Division of Hematology & Oncology, Shands HealthCare and University of Florida, Gainesville, Florida.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Hsu
authors.affiliation: Section of Hematology-Oncology, Baylor College of Medicine Center for Cell and Gene Therapy, Houston, Texas.
authors.forename: Rammurti T
authors.initials: RT
authors.lastname: Kamble
authors.affiliation: Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Hillard M
authors.initials: HM
authors.lastname: Lazarus
authors.affiliation: BMT Unit, Bristol Children's Hospital, Bristol, United Kingdom.
authors.forename: David I
authors.initials: DI
authors.lastname: Marks
authors.affiliation: Bone Marrow & Stem Cell Transplant Program, Oregon Health and Science University, Portland, Oregon.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.affiliation: Pediatric Blood and Marrow Transplant Program, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Division of Hematology/Oncology, Department of Pediatrics, Mattel Children's Hospital at UCLA, Los Angeles, California.
authors.forename: Ami J
authors.initials: AJ
authors.lastname: Shah
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Nirali
authors.initials: N
authors.lastname: Shah
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington.
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.affiliation: Division of Hematology and Oncology, University of North Carolina Hospitals, Chapel Hill, North Carolina.
authors.forename: William A
authors.initials: WA
authors.lastname: Wood
authors.affiliation: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota; Blood & Marrow Transplant Program, Cleveland Clinic, Cleveland, Ohio. Electronic address: nmajhail@nmdp.org.
authors.forename: Navneet S
authors.initials: NS
authors.lastname: Majhail
mesh_terms: D000293:Adolescent; D001842:Bone and Bones / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D019653:Myeloablative Agonists / Q000009:adverse effects; D010020:Osteonecrosis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D019653:Myeloablative Agonists
keywords: Avascular necrosis; Hematopoietic cell transplantation; Late complications