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Moderate-severe grade of chronic graft versus host disease and younger age (less than 45 years old) are risk factors for avascular necrosis in adult patients undergoing allogeneic hematopoietic cell transplantation

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Abstract

Avascular necrosis (AVN) is a debilitating complication of allogeneic hematopoietic cell transplantation (HCT). A retrospective review of 845 patients who underwent HCT was conducted. Cumulative incidence of AVN was 6.3% at 4 years. The following risk factors were significantly associated with AVN risk on univariate analysis: age < 45 (p=0.004), moderate to severe chronic GvHD (p<0.001), reduced intensity conditioning (p=0.02), and a diagnosis of acute leukemia (p=0.045). Multivariate analysis confirmed two risk factors: younger age (<45 years), 9.0% vs 4.4% (p=0.011, hazard ratio (HR) 2.134), and moderate-severe chronic GvHD, 15.4% vs 2.1% (p<0.001, HR 4.950). A risk score model was generated assigning a score to each risk factor. A score of 1 was assigned to moderate-severe GvHD or those with age <45. Total score was calculated, thus dividing patient into three groups: low (score 0, n=349, 41.3%), intermediate (score 1, n=379, 44.9%), and high risk (score 2; n=116, 13.7%). This risk score could stratify the patients according to AVN risk (p<0.001). The risk of AVN was 1.5% in the low risk, 6.2% in the intermediate risk, and 20.8% in the high risk groups. Moderate-severe chronic GvHD and younger age (<45 years) are key risk factors for AVN following allogeneic HCT.

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Author notes

  1. Arjun Datt Law and Sita Bhella contributed equally to this work.

Authors and Affiliations

  1. Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 700 University Ave., Toronto, Ontario, M5G 1Z5, Canada

    Arjun Datt Law, Ivan Pasic, Wilson Lam, Fotios V. Michelis, Armin Gerbitz, Auro Viswabandya, Rajat Kumar, Jeffrey H. Lipton, Jonas Mattsson & Dennis Dong Hwan Kim

  2. Department of Medicine, University of Toronto, Toronto, Canada

    Arjun Datt Law, Sita Bhella, Ivan Pasic, Wilson Lam, Fotios V. Michelis, Armin Gerbitz, Auro Viswabandya, Rajat Kumar, Jeffrey H. Lipton, Jonas Mattsson & Dennis Dong Hwan Kim

  3. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada

    Sita Bhella

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  1. Arjun Datt Law
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Contributions

AL and SB contributed equally to this manuscript. AL and SB contributed to the data analysis, data interpretation, analysis, and manuscript writing. DK contributed to the design of study, the supervision of data collection and of data interpretation, data analysis, and critical revision of the manuscript. IP, WL, FM, AG, AV, JL, RK, JM, and HM were involved in the supervision of the data collection, interpretation of the data, and critical revision of the manuscript.

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Correspondence to Dennis Dong Hwan Kim.

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Law, A.D., Bhella, S., Pasic, I. et al. Moderate-severe grade of chronic graft versus host disease and younger age (less than 45 years old) are risk factors for avascular necrosis in adult patients undergoing allogeneic hematopoietic cell transplantation. Ann Hematol 100, 1311–1319 (2021). https://doi.org/10.1007/s00277-021-04480-5

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