Dynamic relapse prediction by peripheral blood WT1mRNA after allogeneic hematopoietic cell transplantation for myeloid neoplasms.

BACKGROUND

Although various relapse prediction models based on pre-transplant information have been reported, they cannot update the predictive probability considering post-transplant patient status. Therefore, these models are not appropriate for deciding on treatment adjustment and preemptive intervention during post-transplant follow-up. A dynamic prediction model can update the predictive probability by considering the information obtained during follow-up.

OBJECTIVE

This study aimed to develop and assess a dynamic relapse prediction model after allogeneic hematopoietic cell transplantation (allo-HCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) using peripheral blood Wilms' tumor 1 messenger RNA (WT1mRNA).

STUDY DESIGNS

We retrospectively analyzed patients with AML or MDS who underwent allo-HCT at our institution. To develop dynamic models, we employed the landmarking supermodel approach, using age, refined disease risk index, conditioning intensity, and number of transplantations as pre-transplant covariates and both pre- and post-transplant peripheral blood WT1mRNA levels as time-dependent covariates. Finally, we compared the predictive performances of the conventional and dynamic models by area under the time-dependent receiver operating characteristic curves.

RESULTS

A total of 238 allo-HCT cases were included in this study. The dynamic model that considered all pre-transplant WT1mRNA levels and their kinetics showed superior predictive performance compared to models that considered only pre-transplant covariates or factored in both pre-transplant covariates and post-transplant WT1mRNA levels without their kinetics; their time-dependent areas under the curve were 0.89, 0.73, and 0.87, respectively. The predictive probability of relapse increased gradually from approximately 90 days before relapse. Furthermore, we developed a web application to make our model user friendly.

CONCLUSION

This model facilitates real-time, highly accurate, and personalized relapse prediction at any time point after allo-HCT. This will aid decision-making during post-transplant follow-up by offering objective relapse forecasts for physicians.

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest M.H. received honoraria and grants from Otsuka Pharmaceutical Co., Ltd. H.N. received honoraria from Otuka Pharmaceutical Co., Ltd. IY reports grants from KAKENHI, AMED, and Health, Labour and Welfare Policy Research Grants, research fund by Nihon Medi-Physics, and speaker fees from Chugai Pharmaceutical Co, AstraZeneca, and Pfizer outside the submitted work. The remaining authors declare no competing financial interests.