Early Response-Based Therapy Stratification Improves Survival in Adult Early Thymic Precursor Acute Lymphoblastic Leukemia: A Group for Research on Adult Acute Lymphoblastic Leukemia Study.

Bond, Jonathan;Graux, Carlos;Lhermitte, Ludovic;Lara, Diane;Asnafi, Vahid;et.al.
(2017) Journal of Clinical Oncology — Vol. 35, n° 23, p. 2683-2691 (2017)

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Authors
  • Bond, Jonathan
    Author
  • Graux, CarlosUCLouvain
    Author
  • Lhermitte, Ludovic
    Author
  • Lara, Diane
    Author
  • Asnafi, Vahid
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Abstract
Purpose Early thymic precursor (ETP) acute lymphoblastic leukemia (ALL) is an immunophenotypically defined subgroup of T-cell ALL (T-ALL) associated with high rates of intrinsic treatment resistance. Studies in children have shown that the negative prognostic impact of chemotherapy resistance is abrogated by the implementation of early response-based intensification strategies. Comparable data in adults are lacking. Patients and Methods We performed comprehensive clinicobiologic, genetic, and survival analyses of a large cohort of 213 adult patients with T-ALL, including 47 patients with ETP-ALL, treated in the GRAALL (Group for Research on Adult Acute Lymphoblastic Leukemia) -2003 and -2005 studies. Results Targeted next-generation sequencing revealed that the genotype of immunophenotypically defined adult T-ALL is similar to the pediatric equivalent, with high rates of mutations in factors involved in cytokine receptor and RAS signaling (62.2%), hematopoietic development (29.7%), and chemical modification of histones (48.6%). In contrast to pediatric cases, mutations in DNA methylation factor genes were also common (32.4%). We found that despite expected high levels of early bone marrow chemotherapy resistance (87%), the overall prognosis for adults with ETP-ALL treated using the GRAALL protocols was not inferior to that of the non-ETP-ALL group (5-year overall survival: ETP, 59.6%; 95% CI, 44.2% to 72.0% v non-ETP, 66.5%; 95% CI, 58.7% to 73.2%; P = 0.33) and that allogeneic stem-cell transplantation had a beneficial effect in a large proportion of patients with ETP-ALL. Conclusion Our results suggest that the use of response-based risk stratification and therapy intensification abrogates the poor prognosis of adult ETP-ALL.
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Bond, J., Graux, C., Lhermitte, L., Lara, D., Cluzeau, T., Leguay, T., Cieslak, A., Trinquand, A., Pastoret, C., Belhocine, M., Spicuglia, S., Lheritier, V., Leprêtre, S., Thomas, X., Huguet, F., Ifrah, N., Dombret, H., Macintyre, E., Boissel, N., & Asnafi, V. (2017). Early Response-Based Therapy Stratification Improves Survival in Adult Early Thymic Precursor Acute Lymphoblastic Leukemia: A Group for Research on Adult Acute Lymphoblastic Leukemia Study. Journal of Clinical Oncology, 35(23), 2683-2691. https://doi.org/10.1200/JCO.2016.71.8585 (Original work published 2017)