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Acute lymphoblastic leukemia

Prognostic value of Oncogenetic mutations in pediatric T Acute Lymphoblastic Leukemia: a comparison of UKALL2003 and FRALLE2000T protocols

Leukemia volume 36, pages 263–266 (2022)Cite this article

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Historically, T-cell acute lymphoblastic leukaemias (T-ALL) responded less well to treatment than B-Cell precursor ALL (BCP-ALL) and outcome post-relapse is poor. Few T-ALL prognostic markers exist, so stratification is based on early morphological or Minimal Residual Disease (MRD) response, including in the UKALL2003 (2003–2011; ISCTRN07355119) [1, 2] and FRALLE2000T (2000–2010) trials [3].

Petit et al. [3] retrospectively applied an oncogenetic N/F/R/P classifier based on NOTCH1, FBXW7, and N/K-RAS mutations and PTEN mutation/deletion, whereby oncogenetic low-risk (gLoR) patients demonstrated NOTCH1 and/or FBXW7 mutation (N/Fmut) but no RAS or PTEN abnormalities (R/Pwt) and oncogenetic high-risk patients (gHiR) were N/Fwt and/or R/Pmut, to 213 patients achieving complete remission (CR) on the FRALLE2000T protocol. When combined with a d35 MRD cutoff of 0.01%/10−4, this classifier identified a low-risk group (gLoR and MRD < 10−4, 33% of patients) with a 5-year disease-free survival (DFS) of 95% and a high-risk group (gHiR and MRD > 10−4, 23%) with a DFS of 51%.

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Fig. 1: UKALL2003 and FRALLE2000T cohorts.

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Acknowledgements

We would like to thank the UK Childrens Leukaemia Clinicians Network (CLCN) and the French ALL de l’Enfant FRALLE trial and the Société Française de lutte contre les Cancers et les leucémies de l’Enfant et de l’Adolescent (SFCE) for sharing data on UKALL2003 and FRALLE2000T, respectively, and enabling this comparison. We acknowledge Blood Cancer UK (formerly Bloodwise), the Medical Research Council, Children with Cancer, Enfants et Santé, Imagine for Margo, the Ligue National Contre le Cancer and Association Laurette Fugain for financial support. Primary childhood leukemia samples used in this study were provided by the Blood Cancer UK.

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Authors and Affiliations

  1. Royal Marsden Hospital, NHS Foundation Trust, London, UK

    Mary M. Taj

  2. Leukaemia Research Cytogenetics Group, Clinical and Translational Research Institute, Newcastle University, Newcastle upon Tyne, UK

    Anthony V. Moorman & Lina Hamadeh

  3. Department of Pediatric Hematology and Oncology, AP-HP Hôpital Armand Trousseau, Sorbonne Université, UMRS_938, CDR Saint-Antoine, Paris, France

    Arnaud Petit & Fanny Alby-Laurent

  4. Laboratory of Onco-Hematology, AP-HP Hôpital Necker-Enfants Malades, Université de Paris and Institut Necker-Enfants Malades, Paris, France

    Vahid Asnafi & Elizabeth Macintyre

  5. Great Ormond Street Hospital, London, UK

    Ajay Vora

  6. University College London Cancer Institute, London, UK

    Marc R. Mansour & Rosemary Gale

  7. INSERM UMRS 1153, Université de Paris, Paris, France

    Sylvie Chevret

  8. University Hospitals Bristol and Weston, Bristol, UK

    John Moppett

  9. Department of Pediatric Hematology, AP-HP, Hôpital Universitaire Robert Debré, EA 3518, Université de Paris, Paris, France

    André Baruchel

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Contributions

Study conception—MMT, AVM, AP, EM. Manuscript preparation—-MMT, EM, AVM, AP, FAL, AB, AV, JM, VA. Laboratory genetic studies—MRM, RG, VA. Statistics and analysis—LH, AVM, AP, SC.

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Correspondence to Elizabeth Macintyre.

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Taj, M.M., Moorman, A.V., Hamadeh, L. et al. Prognostic value of Oncogenetic mutations in pediatric T Acute Lymphoblastic Leukemia: a comparison of UKALL2003 and FRALLE2000T protocols. Leukemia 36, 263–266 (2022). https://doi.org/10.1038/s41375-021-01334-x

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