Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 Status
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 (M...
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| Published in | HemaSphere Vol. 5; no. 10; pp. e641 - n/a |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Philadelphia, PA
Lippincott Williams & Wilkins
01.10.2021
Lippincott, Williams & Wilkins Wiley |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2572-9241 2572-9241 |
| DOI | 10.1097/HS9.0000000000000641 |
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| Abstract | 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. |
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| AbstractList | 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. 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 identifiedNOTCH1 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. 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. 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.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. |
| Author | Macintyre, Elizabeth Michaux, Katell Touzart, Aurore Aladjidi, Nathalie Subtil, Fabien Trinquand, Amélie Abdo, Chrystelle Jung, Charlotte Garnier, Nathalie Rigaud, Charlotte Bertrand, Yves Plesa, Adriana Petit, Arnaud Chassagne‐Clement, Catherine Asnafi, Vahid Lhermitte, Ludovic |
| AuthorAffiliation | Oncologie Pédiatrique, Institut Gustave Roussy, Villejuif, France Université de Paris and Institut Necker-Enfants Malades, Laboratoire d’Onco-Hématologie, AP-HP Hôpital Necker-Enfants Malades, Paris, France Institut d’Hématologie et d’Oncologie Pédiatrique, Hospices Civiles de Lyon, France Département de Biopathologie, Centre Leon Berard, Lyon, France Service d’Hématologie et d’Oncologie pédiatrique, AP-HP, Hôpital Armand Trousseau, Sorbonne Université, Paris, France Service de Biostatistiques des Hospices Civiles de Lyon, France Unité d’Hématologie et Cancérologie pédiatrique/CEREVANCE, CHU Bordeaux, France Laboratoire d’Hématologie, Hospices Civiles de Lyon, France |
| AuthorAffiliation_xml | – name: Unité d’Hématologie et Cancérologie pédiatrique/CEREVANCE, CHU Bordeaux, France – name: Service de Biostatistiques des Hospices Civiles de Lyon, France – name: Oncologie Pédiatrique, Institut Gustave Roussy, Villejuif, France – name: Département de Biopathologie, Centre Leon Berard, Lyon, France – name: Laboratoire d’Hématologie, Hospices Civiles de Lyon, France – name: Université de Paris and Institut Necker-Enfants Malades, Laboratoire d’Onco-Hématologie, AP-HP Hôpital Necker-Enfants Malades, Paris, France – name: Institut d’Hématologie et d’Oncologie Pédiatrique, Hospices Civiles de Lyon, France – name: Service d’Hématologie et d’Oncologie pédiatrique, AP-HP, Hôpital Armand Trousseau, Sorbonne Université, Paris, France |
| Author_xml | – sequence: 1 givenname: Amélie surname: Trinquand fullname: Trinquand, Amélie organization: National Children's Research Centre at Children's Health, Ireland – sequence: 2 givenname: Adriana surname: Plesa fullname: Plesa, Adriana organization: Hospices Civiles de Lyon – sequence: 3 givenname: Chrystelle surname: Abdo fullname: Abdo, Chrystelle organization: AP‐HP Hôpital Necker‐Enfants Malades – sequence: 4 givenname: Fabien surname: Subtil fullname: Subtil, Fabien organization: Service de Biostatistiques des Hospices Civiles de Lyon – sequence: 5 givenname: Nathalie surname: Aladjidi fullname: Aladjidi, Nathalie organization: CHU Bordeaux – sequence: 6 givenname: Charlotte surname: Rigaud fullname: Rigaud, Charlotte organization: Institut Gustave Roussy – sequence: 7 givenname: Aurore surname: Touzart fullname: Touzart, Aurore organization: AP‐HP Hôpital Necker‐Enfants Malades – sequence: 8 givenname: Ludovic surname: Lhermitte fullname: Lhermitte, Ludovic organization: AP‐HP Hôpital Necker‐Enfants Malades – sequence: 9 givenname: Arnaud surname: Petit fullname: Petit, Arnaud organization: Sorbonne Université – sequence: 10 givenname: Katell surname: Michaux fullname: Michaux, Katell organization: Hospices Civiles de Lyon – sequence: 11 givenname: Charlotte surname: Jung fullname: Jung, Charlotte organization: Hospices Civiles de Lyon – sequence: 12 givenname: Catherine surname: Chassagne‐Clement fullname: Chassagne‐Clement, Catherine organization: Département de Biopathologie, Centre, Leon Berard – sequence: 13 givenname: Vahid surname: Asnafi fullname: Asnafi, Vahid organization: AP‐HP Hôpital Necker‐Enfants Malades – sequence: 14 givenname: Yves surname: Bertrand fullname: Bertrand, Yves organization: Hospices Civiles de Lyon – sequence: 15 givenname: Nathalie surname: Garnier fullname: Garnier, Nathalie organization: Hospices Civiles de Lyon – sequence: 16 givenname: Elizabeth surname: Macintyre fullname: Macintyre, Elizabeth email: elizabeth.macintyre@aphp.fr organization: AP‐HP Hôpital Necker‐Enfants Malades |
| BackLink | https://hal.sorbonne-universite.fr/hal-03350319$$DView record in HAL |
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| Snippet | While outcome for pediatric T lymphoblastic lymphoma (T‐LL) has improved with acute leukemia‐type therapy, survival after relapse remains rare. Few prognostic... While outcome for pediatric T lymphoblastic lymphoma (T-LL) has improved with acute leukemia-type therapy, survival after relapse remains rare. Few prognostic... |
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| Title | Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 Status |
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