Risk factors for positive post-transplantation measurable residual disease in patients with acute lymphoblastic
Yuewen Wang1, Guomei Fu2, Lanping Xu1
1Department of Hematology, Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China.
Background:
The level of measurable residual disease (MRD) before and after transplantation is related to inferior transplant outcomes, and post-hematopoietic stem cell transplantation measurable residual disease (post-HSCT MRD) has higher prognostic value in determining risk than pre-hematopoietic stem cell transplantation measurable residual disease (pre-HSCT MRD). However, only a few work has been devoted to the risk factors for positive post-HSCT MRD in patients with acute lymphoblastic leukemia (ALL). This study evaluated the risk factors for post-HSCT MRD positivity in patients with ALL who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Methods:
A total of 1683 ALL patients from Peking University People's Hospital between January 2009 and December 2019 were enrolled to evaluate the cumulative incidence of post-HSCT MRD. Cox proportional hazard regression models were built for time-to-event outcomes. Multivariable analysis was performed to determine independent influencing factors from the univariable analysis.
Results:
Both in total patients and in T-cell ALL or B-cell ALL, pediatric or adult, human leukocyte antigen-matched sibling donor transplantation or haploidentical SCT subgroups, positive pre-HSCT MRD was a risk factor for post-HSCT MRD positivity ( P <0.001 for all). Disease status (complete remission 1 [CR1] vs . ≥CR2) was also a risk factor for post-HSCT MRD positivity in all patients and in the B cell-ALL, pediatric, or haploidentical SCT subgroups ( P = 0.027; P = 0.003; P = 0.035; P = 0.003, respectively). A risk score for post-HSCT MRD positivity was developed using the variables pre-HSCT MRD and disease status. The cumulative incidence of post-HSCT MRD positivity was 12.3%, 25.1%, and 38.8% for subjects with scores of 0, 1, and 2-3, respectively ( P <0.001). Multivariable analysis confirmed the association of the risk score with the cumulative incidence of post-HSCT MRD positivity and relapse as well as leukemia-free survival and overall survival.
Conclusion:
Our results indicated that positive pre-MRD and disease status were two independent risk factors for post-HSCT MRD positivity in patients with ALL who underwent allo-HSCT.
Insights
Positive pre-transplant measurable residual disease (MRD) and advanced disease status are key risk factors for post-transplant MRD positivity in acute lymphoblastic leukemia (ALL) patients undergoing allogeneic stem cell transplant.
Area of Science:
- Hematology
- Oncology
- Transplantation Immunology
Background:
- Measurable residual disease (MRD) post-hematopoietic stem cell transplantation (HSCT) is a strong predictor of transplant outcomes.
- Limited research exists on risk factors for positive MRD after HSCT in acute lymphoblastic leukemia (ALL).
Purpose of the Study:
- To identify risk factors for positive MRD after allogeneic HSCT (allo-HSCT) in ALL patients.
- To develop a risk score for predicting post-HSCT MRD positivity.
Main Methods:
- Retrospective analysis of 1683 ALL patients undergoing allo-HSCT from 2009-2019.
- Utilized Cox proportional hazard regression and multivariable analysis to identify independent risk factors.
- Developed a risk score based on pre-HSCT MRD and disease status.
Main Results:
- Positive pre-HSCT MRD was a significant risk factor for post-HSCT MRD positivity across subgroups (P < 0.001).
- Disease status (CR1 vs. ≥CR2) also predicted post-HSCT MRD positivity in several subgroups (P ≤ 0.035).
- A risk score incorporating pre-HSCT MRD and disease status effectively predicted cumulative incidence of post-HSCT MRD positivity (P < 0.001).
Conclusions:
- Positive pre-transplant MRD and disease status are independent risk factors for post-HSCT MRD positivity in ALL patients.
- The developed risk score aids in stratifying patients based on their risk of post-HSCT MRD positivity.
- This finding has implications for risk-adapted treatment strategies in ALL post-allo-HSCT.
