Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 Status

• Published in: HemaSphere Vol. 5; no. 10; pp. e641 - n/a
• Main Authors: Trinquand, Amélie, Plesa, Adriana, Abdo, Chrystelle, Subtil, Fabien, Aladjidi, Nathalie, Rigaud, Charlotte, Touzart, Aurore, Lhermitte, Ludovic, Petit, Arnaud, Michaux, Katell, Jung, Charlotte, Chassagne‐Clement, Catherine, Asnafi, Vahid, Bertrand, Yves, Garnier, Nathalie, Macintyre, Elizabeth
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott Williams & Wilkins 01.10.2021; Lippincott, Williams & Wilkins; Wiley
• Subjects: Hematology; Human health and pathology; Life Sciences
• ISSN: 2572-9241; 2572-9241
• DOI: 10.1097/HS9.0000000000000641

While outcome for pediatric T lymphoblastic lymphoma (T‐LL) has improved with acute leukemia‐type therapy, survival after relapse remains rare. Few prognostic markers have been identified: NOTCH1 and/or FBXW7 (N/F) mutations identify good prognosis T‐LL and high‐level minimal disseminated disease (MDD) is reported to be of poor prognosis. We evaluated MDD and/or MRD status by 8‐color flow cytometry and/or digital droplet PCR in 82 pediatric T‐LL treated according to the EURO‐LB02 prednisone reference arm. Both techniques gave identical results for values ≥0.1%, allowing compilation. Unlike historical studies, an MDD threshold of 1% had no prognostic significance. The 54% (42/78) of patients with MDD ≥0.1% had a relatively favorable outcome (5‐y overall survival [OS] 97.6% versus 80.6%, P = 0.015, 5‐y event‐free‐survival [EFS] 95.2% versus 80.6%, P = 0.049). MDD lower than 0.1% had no impact in N/F mutated T‐LL, but identified the N/F germline patient with a high risk of relapse. Combining oncogenetic and MDD status identified 86% of patients (n = 49) with an excellent outcome and 14% of N/F germline/MDD <0.1% patients (n = 8) with poor prognosis (5y‐OS 95.9% versus 37.5%, P < 0.001; 5y‐EFS 93.9% versus 37.5%, P < 0.001). If confirmed by prospective studies, MDD and N/F mutational status would allow identification of a subset of patients who merit consideration for alternative front‐line treatment.