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Adolescent and young adult (AYA) versus pediatric patients with acute leukemia have a significantly increased risk of acute GVHD following unrelated donor (URD) stem cell transplantation (SCT): the Children’s Oncology Group experience

Bone Marrow Transplantation volume 57, pages 445–452 (2022)Cite this article

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Abstract

Adolescent and young adult (AYA) patients with acute leukemia (AL) have inferior outcomes in comparison to younger patients, and are more likely to develop acute and chronic GVHD than younger children following HLA matched sibling donor stem cell transplant (SCT). We compared the incidence of grade II–IV acute GVHD, chronic GVHD, and survival in AYA (age 13–21 years) to younger children (age 2–12 years) who received an unrelated donor SCT for acute leukemia on Children’s Oncology Group trials between 2004–2017. One hundred and eighty-eight children and young adults ages 2–21 years underwent URD SCT. Sixty-three percent were aged 2–12 and 37% were age 13–21. Older age was a risk factor for grade II–IV acute GVHD in multivariate analysis with a hazard ratio (HR) of 1.95 [95% confidence interval (CI) 1.23–3.10], but not for chronic GVHD, HR 1.25 [95% CI 0.57–2.71]. Younger patients relapsed more often (34.5 ± 4.4% vs. 22.8 ± 4.0%, p = 0.032), but their Event-Free Survival (42.6 ± 4.7% vs. 51.8 ± 6.1%, p = 0.18) and Overall Survival at 5 years (48.5 ± 4.9% vs. 51.5 ± 6.4%, p = 0.56) were not different than AYA patients. AYA patients who receive an URD SCT for acute leukemia are significantly more likely to develop grade II–IV acute GVHD, though survival is similar.

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Fig. 1: Cumulative incidence of acute GVHD (grade II–IV) by age (13–21 years vs.2–12 years), among URD recipients.
Fig. 2: Cumulative incidence of chronic GVHD (limited and extensive) by age, among URD recipients.
Fig. 3: Cumulative incidence of chronic GVHD (limited and extensive) by cancer remission status, among URD recipients.
Fig. 4: Event-free Survival of URD recipients by age.
Fig. 5: Cumulative incidence of relapse by age, among URD recipients.

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Acknowledgements

The authors would like to thank the patients and families who participated in the Children’s Oncology Group stem cell transplant trials, as well as the physician investigators who collaborated with the authors. We also appreciate the collaborative efforts of the Cellular Therapy and Adolescent and Young Adult Children’s Oncology Group committees.

Funding

N01 HC-45220/HHSN268200425220C. COG Chair’s grant U10CA098543. U10CA180899. CA98413-08. U10CA180886. R01CA1116660. 2U01HL069254. St. Baldrick’s Foundation

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Authors and Affiliations

  1. Department of Pediatrics, Golisano Children’s Hospital, University of Rochester Medical Center, Rochester, NY, USA

    Jeffrey R. Andolina

  2. Children’s Oncology Group, Monrovia, CA, USA

    Yi-Cheng Wang

  3. Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA

    Lingyun Ji

  4. Transplantation and Cellular Therapy Section, Children’s Hospital Los Angeles Cancer and Blood Disease Institute, USC Keck School of Medicine, Los Angeles, CA, USA

    David R. Freyer & Michael A. Pulsipher

  5. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    John E. Levine

  6. Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO, USA

    Alan S. Gamis

  7. Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Richard Aplenc

  8. Department of Pediatrics, MD Anderson Cancer Center, Houston, TX, USA

    Michael E. Roth

  9. Department of Pediatrics, New York Medical College, Valhalla, NY, USA

    Lauren Harrison & Mitchell S. Cairo

  10. Departments of Pediatrics, Medicine, Pathology, Microbiology and Immunology, Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA

    Mitchell S. Cairo

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Contributions

JRA, LJ, MSC designed the study; YW, LJ collected the data; all authors analyzed and interpreted the results; JRA, LJ, MSC wrote the initial manuscript; all authors edited the manuscript.

Corresponding authors

Correspondence to Jeffrey R. Andolina or Mitchell S. Cairo.

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Competing interests

JL: Ironwood None Personal Fees, Incyte None Consultancy and Research Funding, Kamada None Research Funding, Biogen None non-financial support, Bluebird Bio Consultant Consultancy, Novartis Consultant Consultancy, Viracor Inventor Royalty. MAP: Miltenyi N/A Research Support and Educational honoraria, Adaptive N/A Research Suppor and Educational honoraria, Novartis Advisory Board, Study Steering Committee, Educational honoraria. Mesoblast, Advisory board. MSC: Jazz Advisory Board and Speaker Bureau, Amgen Speaker Bureau, Sanofi Speaker Bureau, Nektar Advisory Board, Servier Speaker Bureau. JA, LJ, YW, DF, AG, RA, and LH have nothing to disclose, financial or otherwise.

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Andolina, J.R., Wang, YC., Ji, L. et al. Adolescent and young adult (AYA) versus pediatric patients with acute leukemia have a significantly increased risk of acute GVHD following unrelated donor (URD) stem cell transplantation (SCT): the Children’s Oncology Group experience. Bone Marrow Transplant 57, 445–452 (2022). https://doi.org/10.1038/s41409-021-01558-6

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