Identification of prognostic factors in childhood T‐cell acute lymphoblastic leukemia: Results from DFCI ALL Consortium Protocols 05‐001 and 11‐001 Academic Article uri icon

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  • BACKGROUND/OBJECTIVES: While outcomes for pediatric T-cell acute lymphoblastic leukemia (T-ALL) are favorable, there are few widely accepted prognostic factors, limiting the ability to risk stratify therapy. DESIGN/METHODS: Dana-Farber Cancer Institute (DFCI) Protocols 05-001 and 11-001 enrolled pediatric patients with newly diagnosed B- or T-ALL from 2005 to 2011 and from 2012 to 2015, respectively. Protocol therapy was nearly identical for patients with T-ALL (N = 123), who were all initially assigned to the high-risk arm. End-induction minimal residual disease (MRD) was assessed by reverse transcription polymerase chain reaction (RT-PCR) or next-generation sequencing (NGS), but was not used to modify postinduction therapy. Early T-cell precursor (ETP) status was determined by flow cytometry. Cases with sufficient diagnostic DNA were retrospectively evaluated by targeted NGS of known genetic drivers of T-ALL, including Notch, PI3K, and Ras pathway genes. RESULTS: The 5-year event-free survival (EFS) and overall survival (OS) for patients with T-ALL was 81% (95% CI, 73-87%) and 90% (95% CI, 83-94%), respectively. ETP phenotype was associated with failure to achieve complete remission, but not with inferior OS. Low end-induction MRD (<10-4 ) was associated with superior disease-free survival (DFS). Pathogenic mutations of the PI3K pathway were mutually exclusive of ETP phenotype and were associated with inferior 5-year DFS and OS. CONCLUSIONS: Together, our findings demonstrate that ETP phenotype, end-induction MRD, and PI3K pathway mutation status are prognostically relevant in pediatric T-ALL and should be considered for risk classification in future trials. DFCI Protocols 05-001 and 11-001 are registered at as NCT00165087 and NCT01574274, respectively.


  • Burns, Melissa A
  • Place, Andrew E
  • Stevenson, Kristen E
  • Gutiérrez, Alejandro
  • Forrest, Suzanne
  • Pikman, Yana
  • Vrooman, Lynda M
  • Harris, Marian H
  • Weinberg, Olga K
  • Hunt, Sarah K
  • O'Brien, Jane E
  • Asselin, Barbara L
  • Athale, Uma
  • Clavell, Luis A
  • Cole, Peter D
  • Gennarini, Lisa M
  • Kahn, Justine M
  • Kelly, Kara M
  • Laverdiere, Caroline
  • Leclerc, Jean‐Marie
  • Michon, Bruno
  • Schorin, Marshall A
  • Sulis, Maria Luisa
  • Welch, Jennifer JG
  • Neuberg, Donna S
  • Sallan, Stephen E
  • Silverman, Lewis B

publication date

  • January 2021

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