Advances in Acute Lymphoblastic Leukemia: A Longitudinal Analysis of Survival Trends and Treatment Modalities
Authors: Sood Aditya , Locke Margaret , Sangari Anish , Wright Jervon , Hou Lilly , Elengickal Joseph , Aung Wint Yan , Singhal Adit , George Riya , Nieto Maria J 
Published: December 2024

Introduction
Acute lymphoblastic leukemia (ALL) is a rapidly progressing leukemia, accounting for approximately 10% of leukemias in the United States. Treatment consists of multiple chemotherapy agents, and advancements in therapy over the past few decades have significantly improved survival rates. This study assesses long-term survival trends and evaluates the effects of different treatment modalities on patients with ALL between the years 1975 and 2019, reflecting the evolution of therapies ranging from chemotherapy to targeted approaches and immunotherapies.
Methods
Data from 14,386 patients who were diagnosed with ALL from the Surveillance, Epidemiology, and End Results (SEER) database was analyzed, examining diagnosis year, chemotherapy, radiation treatment types, histologic subtypes, and age at diagnosis. Survival outcomes were assessed using the Cox proportional hazards model.
Results
Survival rates in patients with ALL improved significantly over the study periods, with hazard ratios (HR) decreasing from baseline in 1975-1979 to HR: 0.13 (95% CI: 0.10-0.17, p &lt; 0.001) in 2015-2019. Chemotherapy was highly beneficial in reducing mortality with HR: 0.57 (95% CI: 0.51-0.62, p &lt; 0.001). In contrast, outcomes from radiation therapy varied. Non-specific radiation showed an increase in mortality (HR: 1.23, 95% CI: 1.13-1.33, p &lt; 0.001), and there was no significant mortality benefit from combined beam and implant radiation (HR: 1.15, 95% CI: 0.29-4.61, p = 0.8). Age at diagnosis significantly influenced survival outcomes, with the best prognosis in very young patients aged 0-4 years (HR: 0.37, 95% CI: 0.30-0.46, p &lt; 0.001), and progressively worsening survival with increasing age, notably after 50 years old (HR for 85+ years: 2.84, 95% CI: 2.23-3.61, p &lt; 0.001). Variability in response was also seen across the different histologic subtypes of ALL.
Discussion/Conclusion
This retrospective analysis underscores the substantial progress achieved in the treatment of ALL over the past four decades, with particularly marked improvements noted in recent years. These improvements in survival are likely due to the development of newer chemotherapeutic agents and regimens. Key innovations include Tyrosine Kinase Inhibitors such as imatinib and ponatinib for Philadelphia chromosome-positive ALL, monoclonal antibodies including blinatumomab and inotuzumab ozogamicin that target specific antigens, and Chimeric Antigen Receptor T-cell therapy that have shown high remission rates in refractory B-cell ALL. Additionally, pediatric-inspired regimens and innovative combination treatments like mini-Hyper-CVD are improving long-term survival and reducing toxicity, especially in older adults. The significant role of age and histological subtype in dictating survival outcomes points to the necessity for personalized and age-adapted treatment protocols. Despite these advances, the variable efficacy of radiation therapy and the nuanced outcomes across different patient subgroups show there are still opportunities for further research into optimizing treatment combinations. This study not only highlights historical progress over the last 5 decades but also emphasizes ongoing challenges and areas for future investigation in the treatment of ALL.