Abstract
Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.
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Acknowledgements
We would like to thank Keith A. Laycock, PhD, ELS for the scientific editing of the manuscript. We thank Dr. Stephen Gottschalk for helpful comments on the manuscript. We would like to thank our colleagues, advanced practice providers, nurses, data managers and other healthcare professional who participated in patient care and data collection. We also would like to thank the parents, who entrusted the care of our children to us. This work was supported by the American Society of Hematology (Scholar Award to AS) and the American Lebanese Syrian Associated Charities (ALSAC).
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AS, SH, CC, and BMT designed the study. AS, YL, IA, HBA, PA, AB, NSB, MBB, JB, CB, JEB, AD, J-HD, HE, MF, AG, NJG, WSG, ESG, KH, RH, MPH, JSH, DJ, KAK, EK, SK, AKK, NAK, YPK, CRL, GL-H, PM, KCM, SN, AO-V, TO, MR, SR, KR, HGR, PAR, MES, PJS, JLS, KS, HJS, MdT, ANU, and BV acquired the data and verified it. AS, SH, RJB, CC, and BMT analyzed the data. AS and BMT wrote the manuscript, and YL, IA, HBA, PA, AB, NSB, MBB, JB, CB, JEB, AD, J-HD, HE, MF, AG, NJG, WSG, ESG, KH, RH, MPH, JSH, DJ, KAK, EK, SK, AKK, NAK, YPK, CRL, GL-H, PM, KCM, SN, AO-V, TO, MR, SR, KR, HGR, PAR, MES, PJS, JLS, KS, HJS, MdT, ANU, and BV critically reviewed the manuscript. All authors agree with and take full responsibility for the content of this manuscript.
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AS’s institution receives support for the conduct of industry sponsored trials from Vertex Pharmaceuticals, CRISPR Therapeutics and Novartis. AS has received consulting fee from Spotlight Therapeutics and Medexus Inc, and honoraria from Vindico Medical Education. HBA reports that she is an employee of BeiGene Ltd and began her employment after the contribution of any clinical data. RJB reports that he currently is an employee of Smith & Nephew, a position that he transitioned to while this project was ongoing. J-HD reports receiving honoraria from blue bird bio, Orchard, Jazz Pharmaceuticals, Novartis, Sanofi Genzyme and Gilead. MPH serves on the advisory board for Mesoblast. NAK has equity interest in Amgen, Johnson and Johnson, Merck and Pfizer and has received financial support for research from Jazz Pharmaceuticals. HJS reports receiving honoraria from Jazz Pharmaceuticals and has a patent US-2020-0163997-A1 with royalties paid. BMT has received financial support for research and travel from Miltenyi Biotec. Remaining authors do not have any conflicts of interest to disclose.
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Sharma, A., Huang, S., Li, Y. et al. Outcomes of pediatric patients with therapy-related myeloid neoplasms. Bone Marrow Transplant 56, 2997–3007 (2021). https://doi.org/10.1038/s41409-021-01448-x
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DOI: https://doi.org/10.1038/s41409-021-01448-x
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