Efficacy of Dose-Adjusted Regimen on Survival in Frail Adults With Acute Lymphoblastic Leukemia

The treatment of acute lymphoblastic leukemia (ALL) in adults represents a therapeutic challenge, particularly in patients with high-risk factors, clinical frailty, or socioeconomic limitations that hinder adherence to intensive outpatient regimens. While protocols such as HyperCVAD have been widely used, their toxicity can be significant in certain subgroups. In this context, the EPOCH regimen has been explored as an inpatient consolidation alternative that allows a gradual transition toward less toxic regimens, with potential benefits in vulnerable populations.

• Patients meeting criteria will receive DA-EPOCH via central line for 5 days every 21 days, with monitoring, supportive care, transfusions, prophylaxis, and G-CSF for 5 doses per cycle (Drug): After patient selection and confirmation of inclusion criteria, the DA-EPOCH treatment regimen will be initiated. It is typically administered through a central line over 5 days, during which adverse events will be closely monitored. Each treatment cycle lasts 21 days. All patients will receive the same level of care as those undergoing high-intensity chemotherapy, including monitoring of transfusion needs, supportive care with prophylactic medications, and the administration of colony-stimulating factors, with a total of 5 doses per cycle. The treatment regimen consists of six cycles, during which intrathecal chemotherapy will be administered to prevent central nervous system relapse. This prophylaxis will be given between each cycle. After completing the six cycles, patients will continue with a maintenance regimen consisting of 6-mercaptopurine at 50 mg/m² of body surface area from Monday to Friday, along with weekly intramuscular methotrexate (50 mg), total duration for 2 years

Primary outcomes

• To determine the proportion of overall survival and disease-free survival [From enrollment until 1 year after the end of treatment.]: For the survival analysis, the Kaplan-Meier method will be used, which is a non-parametric technique employed to estimate the survival function from time-to-event data.

Secondary outcomes

• To determine the proportion of complete remissions (<5% blasts per field) after the first 4 weeks of induction therapy and the proportion of measurable residual disease (proportion of cells) at 6 weeks. [Complete Remision (CR) at 4 weeks after induction and measurable residual disease (MRD) at 6 weeks of treatment.]: Complete remission (CR) will be evaluated by bone marrow aspiration and optical microscopy review at 4 weeks after induction, while measurable residual disease (MRD) will be assessed also by bone marrow aspiration ans measured by flow cytometry at 6 weeks of treatment.
• To establish the proportion of serious adverse events associated with the chemotherapy regimen. [From enrollment until 1 year after the end of treatment.]: These will be graded according to the adverse events scale. The National Comprehensive Cancer Network (NCCN) adverse events scale, known as the 'NCCN Common Terminology Criteria for Adverse Events' (NCCN CTCAE), is a tool used to classify the severity of adverse events that occur during clinical trials of cancer treatments.
• To describe the proportion of severe neutropenia events and treatment-related mortality [From enrollment until 1 year after the end of treatment.]: Neutropenia events associated with chemotherapy will be quantified in each cycle, and their proportion will be established per administered cycle
• To describe the length of hospital stay in days. [From hospital admission to the last day of stay for each administered cycle (each cycle is 21 days).]: The days of hospital stay will be quantified for each cycle of chemotherapy.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Diagnosed with acute lymphoblastic leukemia (ALL) according to the World Health Organization (WHO) criteria
* Older than 18 years old
* ECOG Performance Status Scale >1 or the Karnofsky Performance Status (KPS) <80%.
* Comorbidities: diabetes mellitus, arterial hypertension, thrombotic events, endocrine disorders, or any condition that hinders the administration of full-dose chemotherapy.
* Toxicity prior to a standard chemotherapy regimen.
* Both genders
* Over 18 years of age
* No upper age limit
* Signed informed consent

Exclusion Criteria:

´- Patients refractory to induction treatment

* Patients who have previously received a low-intensity regimen due to comorbidities
* Biphenotypic leukemia
* CNS involvement at diagnosis requiring radiotherapy
* Patients whose survival is expected to be less than 48 hours due to leukemiarelated complications
* Patients with a history of ischemic or hemorrhagic stroke or severe neurological deterioration
* Pregnant patients

• Christian O Ramos, MD, Principal investigator, Hospital General de México Dr. Eduardo Liceaga