A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

Abstract

Background For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT. Methods A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables. Results All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR ( P < 0.001, P = 0.004, and P < 0.001, respectively) and worse LFS ( P < 0.001, P = 0.017, and P < 0.001, respectively), and OS ( P < 0.001, P = 0.009, and P < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 ( P < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score. Conclusion This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

Predictive Value of Dynamic Peri-Transplantation MRD Assessed By MFC Either Alone or in Combination with Other Variables for Outcomes of Patients with T-Cell Acute Lymphoblastic Leukemia

“…In a recent study including 477 B-ALL patients who underwent allo-HSCT, Cao et al [19] demonstrated that post-HSCT MRD, but not pre-HSCT MRD was associated with higher CIR and shorter survival after multivariate analysis. In contrast to the result by Cao et al [19] , we found that both pre-and post-MRD could be used for discriminating patients into different relapse risk groups for T-ALL patients, although post-HSCT MRD was better than pre-HSCT MRD in predicting leukemia relapse (table 2 and fig. 1).…”

“…There was higher percentage of cases in the positive pre-HSCT MRD group receiving haploidentical HSCT than in the negative pre-HSCT group (P=0.014). However, our previous studies demonstrated that, for ALL patients or acute myeloid leukemia patients, haploidentical HSCT had a superior anti-leukemia activity to MSDT [15,17,19,35] . Higher percentages of patients in the positive MRD groups received IFN-γ or DLI for relapse intervention than those of the negative MRD groups either pre-or post-HSCT (P=0.030 or <0.001, respectively) (table 1).…”

“…transplantation outcomes in patients with T-ALL. In addition, we also tried to establish a risk score principally based on the dynamic peri-HSCT MRD combined with other parameters, such as remission status pre-HSCT and onset of chronic GVHD demonstrated by others [12,26,27] and us [2,16,19] , which might provide better relapse risk determination for T-ALL patients.…”

Ferroptosis in Acute Leukemia

“…For now, there are many ways to treat leukemia clinically, but because of drug resistance or relapse, leukemia patients still need more treatment strategies. [15][16][17][18] A number of experiments and epidemiological studies have shown that iron metabolism disorders are related to the occurrence and development of AL. [19][20][21] The occurrence of leukemia involves many genes related to iron metabolism, including hemochromatosis (HFE) gene, transferrin receptor 1 gene, and other genes involved in iron metabolism.…”