Outcomes of pediatric patients with therapy-related myeloid neoplasms

Akshay Sharma; Sujuan Huang; Ying Li; Russell J. Brooke; Ibrahim Ahmed; Heather B. Allewelt; Persis Amrolia; Alice Bertaina; Neel S. Bhatt; Marc B. Bierings; Joshua Bies; Claire Brisset; Jennifer E. Brondon; Ann Dahlberg; Jean Hugues Dalle; Hesham Eissa; Mony Fahd; Adam Gassas; Nicholas J. Gloude; W. Scott Goebel; Erika S. Goeckerman; Katherine Harris; Richard Ho; Michelle P. Hudspeth; Jeffrey S. Huo; David Jacobsohn; Kimberly A. Kasow; Emmanuel Katsanis; Saara Kaviany; Amy K. Keating; Nancy A. Kernan; Yiouli P. Ktena; Colette R. Lauhan; Gerardo López-Hernandez; Paul L. Martin; Kasiani C. Myers; Swati Naik; Alberto Olaya-Vargas; Toshihiro Onishi; Mohamed Radhi; Shanti Ramachandran; Kristie Ramos; Hemalatha G. Rangarajan; Philip A. Roehrs; Megan E. Sampson; Peter J. Shaw; Jodi L. Skiles; Katherine Somers; Heather J. Symons; Marie de Tersant; Allison N. Uber; Birgitta Versluys; Cheng Cheng; Brandon M. Triplett

doi:10.1038/s41409-021-01448-x

Outcomes of pediatric patients with therapy-related myeloid neoplasms

Akshay Sharma, Sujuan Huang, Ying Li, Russell J. Brooke, Ibrahim Ahmed, Heather B. Allewelt, Persis Amrolia, Alice Bertaina, Neel S. Bhatt, Marc B. Bierings, Joshua Bies, Claire Brisset, Jennifer E. Brondon, Ann Dahlberg, Jean Hugues Dalle, Hesham Eissa, Mony Fahd, Adam Gassas, Nicholas J. Gloude, W. Scott GoebelErika S. Goeckerman, Katherine Harris, Richard Ho, Michelle P. Hudspeth, Jeffrey S. Huo, David Jacobsohn, Kimberly A. Kasow, Emmanuel Katsanis, Saara Kaviany, Amy K. Keating, Nancy A. Kernan, Yiouli P. Ktena, Colette R. Lauhan, Gerardo López-Hernandez, Paul L. Martin, Kasiani C. Myers, Swati Naik, Alberto Olaya-Vargas, Toshihiro Onishi, Mohamed Radhi, Shanti Ramachandran, Kristie Ramos, Hemalatha G. Rangarajan, Philip A. Roehrs, Megan E. Sampson, Peter J. Shaw, Jodi L. Skiles, Katherine Somers, Heather J. Symons, Marie de Tersant, Allison N. Uber, Birgitta Versluys, Cheng Cheng, Brandon M. Triplett

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	2997-3007
Number of pages	11
Journal	Bone marrow transplantation
Volume	56
Issue number	12
DOIs	https://doi.org/10.1038/s41409-021-01448-x
State	Published - Dec 2021

ASJC Scopus subject areas

Transplantation
Hematology

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10.1038/s41409-021-01448-x

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Sharma, A., Huang, S., Li, Y., Brooke, R. J., Ahmed, I., Allewelt, H. B., Amrolia, P., Bertaina, A., Bhatt, N. S., Bierings, M. B., Bies, J., Brisset, C., Brondon, J. E., Dahlberg, A., Dalle, J. H., Eissa, H., Fahd, M., Gassas, A., Gloude, N. J., ... Triplett, B. M. (2021). Outcomes of pediatric patients with therapy-related myeloid neoplasms. Bone marrow transplantation, 56(12), 2997-3007. https://doi.org/10.1038/s41409-021-01448-x

Sharma, A, Huang, S, Li, Y, Brooke, RJ, Ahmed, I, Allewelt, HB, Amrolia, P, Bertaina, A, Bhatt, NS, Bierings, MB, Bies, J, Brisset, C, Brondon, JE, Dahlberg, A, Dalle, JH, Eissa, H, Fahd, M, Gassas, A, Gloude, NJ, Goebel, WS, Goeckerman, ES, Harris, K, Ho, R, Hudspeth, MP, Huo, JS, Jacobsohn, D, Kasow, KA, Katsanis, E, Kaviany, S, Keating, AK, Kernan, NA, Ktena, YP, Lauhan, CR, López-Hernandez, G, Martin, PL, Myers, KC, Naik, S, Olaya-Vargas, A, Onishi, T, Radhi, M, Ramachandran, S, Ramos, K, Rangarajan, HG, Roehrs, PA, Sampson, ME, Shaw, PJ, Skiles, JL, Somers, K, Symons, HJ, de Tersant, M, Uber, AN, Versluys, B, Cheng, C & Triplett, BM 2021, 'Outcomes of pediatric patients with therapy-related myeloid neoplasms', Bone marrow transplantation, vol. 56, no. 12, pp. 2997-3007. https://doi.org/10.1038/s41409-021-01448-x

@article{55008408cf144a7ca9f9388b0be1f7c0,

title = "Outcomes of pediatric patients with therapy-related myeloid neoplasms",

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.",

author = "Akshay Sharma and Sujuan Huang and Ying Li and Brooke, {Russell J.} and Ibrahim Ahmed and Allewelt, {Heather B.} and Persis Amrolia and Alice Bertaina and Bhatt, {Neel S.} and Bierings, {Marc B.} and Joshua Bies and Claire Brisset and Brondon, {Jennifer E.} and Ann Dahlberg and Dalle, {Jean Hugues} and Hesham Eissa and Mony Fahd and Adam Gassas and Gloude, {Nicholas J.} and Goebel, {W. Scott} and Goeckerman, {Erika S.} and Katherine Harris and Richard Ho and Hudspeth, {Michelle P.} and Huo, {Jeffrey S.} and David Jacobsohn and Kasow, {Kimberly A.} and Emmanuel Katsanis and Saara Kaviany and Keating, {Amy K.} and Kernan, {Nancy A.} and Ktena, {Yiouli P.} and Lauhan, {Colette R.} and Gerardo L{\'o}pez-Hernandez and Martin, {Paul L.} and Myers, {Kasiani C.} and Swati Naik and Alberto Olaya-Vargas and Toshihiro Onishi and Mohamed Radhi and Shanti Ramachandran and Kristie Ramos and Rangarajan, {Hemalatha G.} and Roehrs, {Philip A.} and Sampson, {Megan E.} and Shaw, {Peter J.} and Skiles, {Jodi L.} and Katherine Somers and Symons, {Heather J.} and {de Tersant}, Marie and Uber, {Allison N.} and Birgitta Versluys and Cheng Cheng and Triplett, {Brandon M.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = dec,

doi = "10.1038/s41409-021-01448-x",

language = "English (US)",

volume = "56",

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journal = "Bone marrow transplantation",

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TY - JOUR

T1 - Outcomes of pediatric patients with therapy-related myeloid neoplasms

AU - Sharma, Akshay

AU - Huang, Sujuan

AU - Li, Ying

AU - Brooke, Russell J.

AU - Ahmed, Ibrahim

AU - Allewelt, Heather B.

AU - Amrolia, Persis

AU - Bertaina, Alice

AU - Bhatt, Neel S.

AU - Bierings, Marc B.

AU - Bies, Joshua

AU - Brisset, Claire

AU - Brondon, Jennifer E.

AU - Dahlberg, Ann

AU - Dalle, Jean Hugues

AU - Eissa, Hesham

AU - Fahd, Mony

AU - Gassas, Adam

AU - Gloude, Nicholas J.

AU - Goebel, W. Scott

AU - Goeckerman, Erika S.

AU - Harris, Katherine

AU - Ho, Richard

AU - Hudspeth, Michelle P.

AU - Huo, Jeffrey S.

AU - Jacobsohn, David

AU - Kasow, Kimberly A.

AU - Katsanis, Emmanuel

AU - Kaviany, Saara

AU - Keating, Amy K.

AU - Kernan, Nancy A.

AU - Ktena, Yiouli P.

AU - Lauhan, Colette R.

AU - López-Hernandez, Gerardo

AU - Martin, Paul L.

AU - Myers, Kasiani C.

AU - Naik, Swati

AU - Olaya-Vargas, Alberto

AU - Onishi, Toshihiro

AU - Radhi, Mohamed

AU - Ramachandran, Shanti

AU - Ramos, Kristie

AU - Rangarajan, Hemalatha G.

AU - Roehrs, Philip A.

AU - Sampson, Megan E.

AU - Shaw, Peter J.

AU - Skiles, Jodi L.

AU - Somers, Katherine

AU - Symons, Heather J.

AU - de Tersant, Marie

AU - Uber, Allison N.

AU - Versluys, Birgitta

AU - Cheng, Cheng

AU - Triplett, Brandon M.

PY - 2021/12

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N2 - 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.

AB - 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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ER -

Outcomes of pediatric patients with therapy-related myeloid neoplasms

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