Editor's note: The prognosis of high-risk acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains variable, particularly concerning minimal residual disease (MRD) status. Professor Yu Hu and others conducted a retrospective analysis aiming to assess the efficacy of intensified conditioning regimens, namely total marrow and lymphoid irradiation (TMLI)/etoposide/cyclophosphamide (CY) and busulfan (BU)/etoposide/CY, for high-risk ALL patients in complete remission but with varying MRD statuses. Data from 141 patients treated between October 2016 and November 2022 were analyzed. MRD status was assessed using flow cytometry and quantitative real-time polymerase chain reaction (RQ-PCR). The study compared outcomes between 61 patients receiving TMLI/VP16/CY and 80 patients undergoing BU/VP16/CY. Results showed no significant difference in the 2-year relapse rate, disease-free survival (DFS), overall survival (OS), transplant-related mortality (TRM), and graft-versus-host disease (GVHD) occurrence between MRD-negative and MRD-positive patients. Multivariable analysis indicated no significant differences in relapse, OS, or DFS based on conditioning regimen types. These findings suggest that intensified conditioning regimens may mitigate the adverse prognostic influence of pre-transplant MRD positivity in high-risk ALL patients undergoing allo-HSCT. However, large-scale prospective trials are warranted to validate these results further.Introduction
High-risk acute lymphoblastic leukemia (ALL) poses challenges in treatment, particularly in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Minimal residual disease (MRD) status has emerged as a significant prognostic factor in this population. Our study aimed to evaluate the efficacy of intensified conditioning regimens in improving outcomes for high-risk ALL patients with positive MRD status undergoing allo-HSCT.
Methods
This retrospective analysis drew data from 141 patients diagnosed with high-risk acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between October 2016 and November 2022. Patients were selected based on the diagnosis of high-risk ALL and the receipt of allo-HSCT. The study aimed to compare the efficacy of two intensified conditioning regimens: total marrow and lymphoid irradiation (TMLI)/etoposide/cyclophosphamide (CY) and busulfan (BU)/etoposide/CY. Of the 141 individuals, 61 received TMLI/VP16/CY, while 80 underwent BU/VP16/CY.
MRD status before transplantation was determined using both flow cytometry and quantitative real-time polymerase chain reaction (RQ-PCR), allowing for comprehensive assessment. This methodological approach ensured the accurate categorization of patients into MRD-negative and MRD-positive groups, enabling a robust comparative analysis. Statistical methods, including the Mann-Whitney U-test for continuous data and the Kaplan-Meier technique for survival outcomes, were employed to analyze the data, ensuring rigorous evaluation of the treatment outcomes.
Results
The analysis revealed several key findings regarding the efficacy of intensified conditioning regimens for high-risk ALL patients undergoing allo-HSCT. Notably, there was no statistically significant difference in the 2-year relapse rate between MRD-negative and MRD-positive patients, indicating that MRD status did not significantly impact the risk of disease recurrence following transplantation. Similarly, the 2-year disease-free survival (DFS) and overall survival (OS) rates did not exhibit significant discrepancies between the two groups, suggesting comparable long-term outcomes irrespective of MRD status.
Moreover, transplant-related mortality (TRM) and the occurrence of graft-versus-host disease (GVHD) did not show notable variations between MRD-negative and MRD-positive patients, underscoring the overall safety and tolerability of the intensified conditioning regimens. Multivariable analysis further confirmed that variables such as haploidentical versus nonhaploidentical transplants, chronic GVHD, and conditioning regimen types did not yield significant differences in relapse, OS, or DFS outcomes.
These results provide compelling evidence suggesting that intensified conditioning regimens, including TMLI/VP16/CY and BU/VP16/CY, effectively mitigate the adverse prognostic influence of pre-transplant MRD positivity in high-risk ALL patients undergoing allo-HSCT. The comparable outcomes observed across MRD status groups underscore the potential of these regimens to improve treatment efficacy and enhance long-term survival rates in this patient population.
Discussion
The findings of this study have significant implications for the clinical management of high-risk ALL patients undergoing allo-HSCT, particularly those with positive MRD status. By demonstrating the comparable efficacy of intensified conditioning regimens regardless of MRD status, this study highlights the potential of these treatment approaches to address the challenges associated with MRD positivity and improve patient outcomes.
Importantly, the acceptable levels of regimen-related toxicities and TRM observed in this study support the feasibility and safety of intensified conditioning regimens in high-risk ALL patients undergoing allo-HSCT. These findings alleviate concerns regarding the potential adverse effects of intensified conditioning, thus providing clinicians with greater confidence in adopting these approaches in clinical practice.
However, despite the promising results obtained in this retrospective analysis, the authors acknowledge the need for further validation through large-scale prospective clinical trials. Such trials would provide more robust evidence regarding the efficacy and safety of intensified conditioning regimens in high-risk ALL patients with positive MRD status, thus informing evidence-based treatment guidelines and improving patient outcomes in the future.
Conclusion
In conclusion, this retrospective analysis underscores the potential of intensified conditioning regimens, specifically total marrow and lymphoid irradiation (TMLI)/etoposide/cyclophosphamide (CY) and busulfan (BU)/etoposide/CY, in improving outcomes for high-risk acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), irrespective of minimal residual disease (MRD) status. The study demonstrated comparable rates of relapse, disease-free survival (DFS), and overall survival (OS) between MRD-negative and MRD-positive patients, indicating that intensified conditioning regimens effectively mitigate the adverse prognostic influence of MRD positivity.
Furthermore, the analysis revealed acceptable levels of transplant-related mortality (TRM) and graft-versus-host disease (GVHD) occurrence, highlighting the safety and tolerability of these regimens in the study population. Multivariable analysis confirmed that conditioning regimen types did not significantly impact relapse, OS, or DFS outcomes, supporting the efficacy of both TMLI/VP16/CY and BU/VP16/CY in high-risk ALL patients undergoing allo-HSCT.
The open-access article, authored by Xiaoyan Zhao and Ziwei Xu sharing first authorship, and corresponding authors Yu Hu and Huafang Wang, originates from the Department of Hematology, Department of Pediatrics, and Department of Pathology at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China. Published in “Cancer Medicine,” a journal by John Wiley & Sons Ltd, the paper explores intensified conditioning regimens for high-risk acute lymphoblastic leukemia (ALL) patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Top of Form
