Adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation and tyrosine kinase inhibitors: development and validation of a clinical prediction model based on cytogenetics, IKZF1 deletions and minimal residual disease.

Abstract

The aim of this study was to develop and validate a nomogram predicting progression-free survival (PFS) for adult patients with positive acute lymphoblastic leukemia(Ph + ALL) who have undergone allogeneic hematopoietic stem cell transplantation(allo-HSCT) and tyrosine kinase inhibitor(TKI) treatment. Data were retrospectively collected from 176 adult patients diagnosed with Ph + ALL and treated with allo-HSCT and TKIs at The First Affiliated Hospital, Zhejiang University School of Medicine, between January 2015 and May 2023. 70% of the patients were randomly assigned to the training group(n = 124) and 30% of the patients were assigned to the validation group(n = 52). Univariate Cox regression analysis and Akaike Information Criterion(AIC) were utilized to identify significant predictive factors, leading to the development of a nomogram designed to forecast the probability of PFS at 6, 9, and 12 months post-transplantation. The final nomogram incorporated three key variables: presence of complex additional cytogenetic abnormalities (ACAs), minimal residual disease (MRD) status prior to allo-HSCT, and IKZF1 gene deletions. The calibration curves showed excellent consistency between the nomogram prediction and actual observation for 6-, 9- and 12-month PFS in the training set and validation set. The C-index of the training set was 0.726(95%CI: 0.635-0.816), which was no significantly different from the validation set(C-index = 0.774, 95%CI: 0.674-0.875, P > 0.05). This study may provide a simple and efficient prediction model for patients with Ph + ALL undergoing allo-HSCT and TKIs, which can accurately predict PFS subsequent to transplantation. This tool could potentially aid clinicians in decision-making processes and improve patient outcomes.