Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation - Archive ouverte HAL Access content directly
Journal Articles Leukemia Year : 2020

Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation

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Elizabeth Macintyre
Norbert Ifrah
  • Function : Author
  • PersonId : 992780
Ludovic Lhermitte

Abstract

The prognostic value of IL7-receptor pathway (IL7Rp) mutations in T-cell acute lymphoblastic leukemia (T-ALL) remains unclear. We performed a comprehensive study of 200 adult patients with TALL included in the GRAALL2003/2005 protocols to address the clinical significance of IL7Rp mutations. Next-generation sequencing of the IL7Rp (IL7R/JAK1/ JAK3/STAT5B) revealed that IL7Rp mutations were frequent in adult TALL (28%) particularly in immature/early T-cell progenitor (ETP)-ALL. They were associated with mutations of NOTCH-pathway, PHF6, and PRC2 components but not with K/NRAS. IL7Rp mutated (IL7Rp mut) TALL were slow-responders, with a high rate of M2/M3 day-8 marrow compared with IL7Rp non-mutated (IL7Rp WT) TALL (p = 0.002) and minimal residual disease positivity at 6-weeks (MRD1) (p = 0.008) but no difference in MRD2 positivity at 12-weeks. Despite this, no adverse prognosis was evidenced when censored for allogeneic hematopoietic stem cell transplantation (HSCT). In time-dependent analysis, HSCT did not benefit IL7Rp mut patients whereas it was of marked benefit to IL7Rp WT cases. IL7Rp-mutations identify a subgroup of slow-responder T-ALLs which benefit from post-induction chemotherapy regimens but not from HSCT. Our data suggest that prior knowledge of the mutation status of IL7Rp may influence HSCT decision and help to guide therapy reduction.
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inserm-02551756 , version 1 (23-04-2020)

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Rathana Kim, Nicolas Boissel, Aurore Touzart, Thibaut Leguay, Florian Thonier, et al.. Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation. Leukemia, 2020, Epub ahead of print. ⟨10.1038/s41375-019-0685-4⟩. ⟨inserm-02551756⟩
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