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Kids First: T Cell ALL
Kids First Data Resource
Data Resource:  Kids First Data Resource
Point of Contact:  
Allison Heath,  
Project

About This Dataset
The outcome for patients with relapsed T-ALL is dismal with 3-year event free survival of <15%. Thus, the primary goal in the treatment of T-ALL is to prevent relapse, which requires accurate risk stratification. Unfortunately, no genetic alterations have been identified to date that are reproducibly prognostic independent of minimal residual disease (MRD), making it difficult at diagnosis to identify which patients are more likely to relapse. AALL0434 was a Children's Oncology Group-initiated phase 3 randomized clinical trial comparing Capizzi-style escalating methotrexate plus pegaspargase (CMTX) vs. high dose methotrexate (HDMTX), with/without six 5-day courses of nelarabine. Survival on this study was superior to any prior trial for de novo T-ALL, changing the standard of care. Yet, a substantial minority (~15%) of patients had relapsed or refractory (r/r) disease. Through the TARGET initiative, RNA sequencing, DNA copy number analysis, and whole-exome sequencing were performed on 264 T-ALL patients treated on AALL0434, demonstrating recurrent alterations could be grouped into 10 different potentially targetable functional pathways. This analysis was not powered to examine associations between genetic lesions with outcome, because too few patients with r/r disease were included. This project is dedicated to testing the hypothesis that comprehensive genomic profiling of the entire AALL0434 cohort will identify recurrent genetic alterations that can be segregated into biologically relevant deregulated pathways that can be combined with MRD to identify patients at risk for poor outcomes before they relapse and provide rationale for treatment with alternative therapies. In addition, a number of small recent studies demonstrated that many of the biologically relevant alterations in T-ALL occur in non-coding regions of the genome, but no large studies have performed whole genome sequencing in T-ALL. This project also tests the hypothesis that whole genome sequencing of a large cohort of patients with T-ALL will identify novel lesions in coding and non-coding regions that will be highly impactful in the understanding of T-ALL pathogenesis. These hypotheses are tested by performing comprehensive genomic profiling (whole genome sequencing, whole exome sequencing, RNA sequencing, and copy number analysis) of the entire AALL0434 cohort with available samples with the following specific aims: (1) identify recurrent genetic alterations that predict poor outcome in T-ALL; (2) identify novel alterations, including non-coding alterations in T-ALL; and (3) identify germline genetic variants that predispose to T-ALL and to increased toxicity to chemotherapy.
Core Data Elements
Number of Cases
1,358
Case Sex
Female (356); Male (1,002)
Case Age At Diagnosis
0 to 4 years (268); 5 to 9 years (471); 10 to 14 years (357); 15 to 19 years (181); Pediatric and Young Adult (<40 years) (81)
Case Race
American Indian or Alaska Native (4); Asian (71); Black or African American (174); Native Hawaiian or Other Pacific Islander (11); White (966); Unknown (132)
Case Ethnicity
Hispanic or Latino (190); Not Hispanic or Latino (1,116); Unknown (52)
Case Disease Diagnosis
T-Cell Acute Lymphoblastic Leukemia (1,358)
Case Proband
Yes (1,358); No ()
Number of Samples
3,486
Sample Assay Method
RNA Sequencing (1,043); Whole Exome Sequencing (1,085); Whole Genome Sequencing (1,358)
Additional Data Elements
DBGAP STUDY IDENTIFIER
DATA REPOSITORY
Grant Information
261200800001E-12-0-40
Therapeutically Applicable Research to Generate Effective Treatments (TARGET)
HHSN261200800001E
U10CA180886
COG NCTN Network Group Operations Center
Charts
Male (1,002); Female (356)
1,002Male