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. 2021 Dec;56(12):2997-3007.
doi: 10.1038/s41409-021-01448-x. Epub 2021 Sep 3.

Outcomes of pediatric patients with therapy-related myeloid neoplasms

Akshay Sharma  1 , Sujuan Huang  2 , Ying Li  3 , Russell J Brooke  2 , Ibrahim Ahmed  4 , Heather B Allewelt  5 , Persis Amrolia  6 , Alice Bertaina  7 , Neel S Bhatt  8 , Marc B Bierings  9 , Joshua Bies  10 , Claire Brisset  11 , Jennifer E Brondon  12 , Ann Dahlberg  8 , Jean-Hugues Dalle  11 , Hesham Eissa  13 , Mony Fahd  11 , Adam Gassas  14 , Nicholas J Gloude  15 , W Scott Goebel  16 , Erika S Goeckerman  12 , Katherine Harris  17 , Richard Ho  18 , Michelle P Hudspeth  19 , Jeffrey S Huo  20 , David Jacobsohn  17 , Kimberly A Kasow  10 , Emmanuel Katsanis  21 , Saara Kaviany  18 , Amy K Keating  22 , Nancy A Kernan  23 , Yiouli P Ktena  24 , Colette R Lauhan  15 , Gerardo López-Hernandez  25 , Paul L Martin  12 , Kasiani C Myers  26   27 , Swati Naik  28 , Alberto Olaya-Vargas  25 , Toshihiro Onishi  28 , Mohamed Radhi  4 , Shanti Ramachandran  29 , Kristie Ramos  21 , Hemalatha G Rangarajan  30 , Philip A Roehrs  20 , Megan E Sampson  26   27 , Peter J Shaw  31 , Jodi L Skiles  16 , Katherine Somers  30 , Heather J Symons  24 , Marie de Tersant  11 , Allison N Uber  19 , Birgitta Versluys  9 , Cheng Cheng  2 , Brandon M Triplett  3
Affiliations

Outcomes of pediatric patients with therapy-related myeloid neoplasms

Akshay Sharma et al. Bone Marrow Transplant. 2021 Dec.

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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Figures

Figure 1.
Figure 1.
Outcomes following HCT for tMN. Plots showing (a) overall survival, (b) event-free survival, (c) cumulative incidence of relapse and (d) cumulative incidence of non-relapse mortality stratified by the conditioning intensity (MAC versus RIC).
Figure 2.
Figure 2.
Multivariable analysis of risk factors associated with overall survival after HCT for tMN. A forest plot showing the hazard ratio and 95% confidence intervals associated with variables assessed in a multivariable model with mortality being the primary endpoint. Adjusted P value from the Cox proportional hazards model is shown. Analysis sample includes all non-missing variables in the model (n=196). HR of graft source (cord) cannot be estimated because it coincides the donor type (cord) category.
Figure 3.
Figure 3.
Multivariable analysis of risk factors associated with event-free survival after HCT for tMN. A forest plot showing the hazard ratio and 95% confidence intervals associated with variables assessed in a multivariable model with relapse or death being the primary endpoint. Squares represent the hazard ratio and the horizontal bars extend from the lower limit to the upper limit of the 95% confidence interval of the estimate of the hazard ratio. Adjusted P value from the Cox proportional hazards model is shown. Analysis sample includes all non-missing variables in the model (n=197). HR of graft source (cord) cannot be estimated because it coincides the donor type (cord) category.
Figure 4.
Figure 4.
Multivariable analysis of risk factors associated with relapse after HCT for tMN. A forest plot showing the hazard ratio and 95% confidence intervals associated with variables assessed in a multivariable model with relapse as the primary endpoint. Squares represent the hazard ratio and the horizontal bars extend from the lower limit to the upper limit of the 95% confidence interval of the estimate of the hazard ratio. Adjusted P value from Fine and Gray’s regression model is shown. Analysis sample includes all non-missing variables in the model (n=239).
Figure 5.
Figure 5.
Multivariable analysis of risk factors associated with non-relapse mortality after HCT for tMN. A forest plot showing the hazard ratio and 95% confidence intervals associated with variables assessed in a multivariable model with non-relapse mortality being the primary endpoint. Squares represent the hazard ratio and the horizontal bars extend from the lower limit to the upper limit of the 95% confidence interval of the estimate of the hazard ratio. Adjusted P value from Fine and Gray’s regression model is shown. Analysis sample includes all non-missing variables in the model (n=217). HR of graft source (cord) cannot be estimated because it coincides the donor type (cord) category.
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