Outcomes of T-ALL and T-LLy patients who do not enroll on clinical trials due to critical status at presentation
Clinical trials exist to push forward the development of new therapies and to help improve the survival of patients. Advances in therapies over the last few decades have significantly improved the event-free survival (EFS) rates for T-ALL/T-LLy patients. However, relapsed disease still has a poor prognosis. Recently, the Children’s Oncology Group (COG) trial AALL0434 tested the drug nelarabine as a treatment for pediatric T-ALL. This trial showed that adding nelarabine to the patients’ therapies greatly improved disease-free survival for T-ALL pediatric patients. However, a decent portion of patients with T-ALL/T-LLy at initial diagnosis present with significant hyperleukocytosis and large mediastinal masses. Both of these presentations require intensive care unit admissions and emergent therapy. Due to the severity of the presentation and the need to make a rapid diagnosis to initiate therapy as quickly as possible, these patients are less likely to enroll in clinical trials. There is not time to go through a proper clinical trial informed consent process before starting treatment. This means that T-ALL/T-LLy patients who presented in a more critical state were unable to be randomized to receive a new drug. At Children’s Hospital of Philadelphia (CHOP), we diagnose 10-15 children and adolescents a year with T-ALL/T-LLy and have extensive data on at least 150 patients over the past 15-20 years to analyze. Dr. Sumit Gupta of the University of Toronto has a pre-existing database of T-ALL/T-LLy pediatric patients treated in the Province of Ontario for a similar time period. We will abstract the CHOP charts and combine with the pre-existing Ontario database to analyze factors such as utilization of the ICU at diagnosis, presence of mediastinal mass and/or hyperleukocytosis, use of emergent steroids and timing to initiation of systemic chemotherapy, ability to obtain a staging spinal tap prior to initiation of chemotherapy, and ability to enroll into a COG clinical trial. We will then look at outcomes and use univariate and multivariate analyses to determine the relationship between various factors at diagnosis, enrollment onto clinical trials, and likelihood of event-free survival. We hope this analysis will allow us to address two overarching aims. Aim 1: Compare outcomes of newly diagnosed patients with T-ALL/T-LLy unable to enroll into a COG clinical trial due to critical medical status with those who do enroll . Aim 2: Compare outcomes of T-ALL/T-LLy patients who enrolled into a COG clinical trial with those who presented when trials were not actively enrolling regardless of medical status.
