Acute Lymphoblastic Leukemia (ALL) is a malignant hematologic tumor characterized by the clonal proliferation of immature lymphocytes in the bone marrow, peripheral blood, and extramedullary tissues. ALL predominantly affects children and generally has a favorable prognosis, with a 5-year disease-free survival rate reaching 80-90%. Adult ALL accounts for 20-30% of acute leukemias in adults, with nearly two-thirds of these cases being Ph-negative ALL. Historically treated with adult protocols, although remission rates are high, the relapse rate is significant, leading to poor long-term survival. Drawing from the successful experiences in pediatric ALL, using pediatric-inspired regimens for treating adult ALL, especially in adolescents and young adults, is currently recommended internationally. In China, the concept of using pediatric-inspired regimens for treating adult ALL started later, and there is a lack of large-scale prospective clinical research data on this approach. Over the past decade, the Leukemia Diagnosis and Treatment Center of the Institute of Hematology, Chinese Academy of Medical Sciences (CAMS), has continuously optimized chemotherapy protocols for adult ALL, conducted prospective clinical studies, and implemented a comprehensive treatment plan suitable for adult Ph-negative ALL in China (IH-2014 protocol, ChiCTR-OOC-15006328).
Recently, the team led by Jianxiang Wang from the Institute of Hematology, Chinese Academy of Medical Sciences (CAMS), published an article online in “Haematologica” (IF=10.1) titled “Pediatric-inspired regimen for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: a prospective study from China.” The article reports the research outcomes of the IH-2014 protocol. This cohort represents the largest single-center prospective cohort in China for treating adult ALL with a pediatric-inspired regimen, showcasing the advanced level of adult ALL treatment in the country to the international community.
This study included a total of 415 newly diagnosed adult Ph-negative ALL patients treated with the IH-2014 regimen from April 2014 to December 2021. The median age was 27 years (range 14-65 years), and the median follow-up time was 40.8 months. The overall cohort’s 5-year overall survival (OS) rate and disease-free survival (DFS) rate were 53.8% and 51.1%, respectively, with a chemotherapy-related mortality rate of 3.6%. Among the patients who achieved complete remission (CR) after induction therapy and had measurable residual disease (MRD) data available for analysis, totaling 389 patients, were categorized based on risk at diagnosis: 73 patients (18.8%) in the standard-risk group with negative MRD (SR-MRDneg) after induction (<0.01%), 69 patients (17.7%) in the standard-risk group with positive MRD (SR-MRDpos) after induction (≥0.01%), 120 patients (30.8%) in the high-risk group with negative MRD (HR-MRDneg) after induction, and 127 patients (32.6%) in the high-risk group with positive MRD (HR-MRDpos) after induction. The 5-year OS rates for these four groups were 82.6%, 58.7%, 58.3%, and 36.1%, respectively (P<0.001). The 5-year cumulative relapse rates were 24.2%, 41.1%, 36.3%, and 50.1%, respectively (P<0.001). Multivariate analysis revealed that age ≥40 years and positive MRD status after induction were independent prognostic factors for adverse effects on OS and DFS.
In summary, the IH-2014 regimen demonstrates definitive efficacy and good tolerance in adult Ph-negative ALL patients, with individuals under 40 years old benefiting more significantly from the pediatric-inspired protocol. Traditional prognostic factors combined with MRD levels after induction therapy provide a reliable prediction for long-term survival and relapse in adult Ph-negative ALL patients, guiding the selection of allogeneic hematopoietic stem cell transplantation for patients achieving their first complete remission (CR1).
Dr. Jianxiang Wang, Chief Physician at the Institute of Hematology, Chinese Academy of Medical Sciences (CAMS), is the corresponding author of the study, with Dr. Xiaoyuan Gong, Associate Chief Physician at the same institute, as the first author. The project received support from the National Key R&D Program and the National Natural Science Foundation of China.
Reference：1. Pui CH, Yang JJ, Hunger SP, et al. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J Clin Oncol. 2015;33(27):2938-2948.2. Patrick AB, Bijal S, Anjali A, et al. Acute Lymphoblastic Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(9):1079-1109.
