A comprehensive model to predict severe acute graft-versus-host disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation

Meng-Zhu Shen, Shen-Da Hong, Rui Lou, Rui-Ze Chen, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Dong Mo, Meng-Zhu Shen, Shen-Da Hong, Rui Lou, Rui-Ze Chen, Xiao-Hui Zhang, Lan-Ping Xu, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Dong Mo

Abstract

Background: Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT.

Methods: Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://ichgcp.net/clinical-trials-registry/NCT03756675" title="See in ClinicalTrials.gov">NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort.

Results: The equation was as follows: Probability (grade III-IV aGVHD) = [Formula: see text], where Y = -0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) - 0.0089 × (CD8 + cell counts in graft) - 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III-IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9-6.3%) versus 12.8% (95% CI 7.4-18.2%) (P = 0.001), 3.2% (95% CI 1.2-5.1%) versus 10.6% (95% CI 4.7-16.5%) (P = 0.006), and 6.1% (95% CI 1.3-10.9%) versus 19.4% (95% CI 6.3-32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III-IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II-IV and grade I-IV aGVHD.

Conclusions: We established a model which could predict the development of severe aGVHD in HID HSCT recipients.

Keywords: Acute graft-versus-host disease; Acute leukemia; Haploidentical donor; Hematopoietic stem cell transplant; Predicted model.

Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Flow diagram of building machine learning model
Fig. 2
Fig. 2
ROC curve and confusion matrix for grade III to IV aGVHD model in the training (A) and validation cohort (B)
Fig. 3
Fig. 3
The 100-day cumulative incidence of grade III to IV aGVHD in the low- and high-risk groups in total (A), training (B), and validation (C) cohort, and D the rates of grade III to IV aGVHD of each organ in the low- and high-risk group
Fig. 4
Fig. 4
The association between predicted model and other GVHD endpoint in total population. A The 100-day cumulative incidence of grade II to IV aGVHD in the low- and high-risk groups; B The rate of grade II to IV aGVHD of each organ in the low- and high-risk groups; C The 100-day cumulative incidence of grade I–IV aGVHD in the low- and high-risk groups; D The rate of grade I to IV aGVHD of each organ in the low- and high-risk groups

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