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

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://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) = 11+exp(-Y), 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.