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...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-10-01
|
| Series: | HemaSphere |
| Online Access: | http://journals.lww.com/10.1097/HS9.0000000000000641 |
| _version_ | 1827334989499334656 |
|---|---|
| author | Amélie Trinquand Adriana Plesa Chrystelle Abdo Fabien Subtil Nathalie Aladjidi Charlotte Rigaud Aurore Touzart Ludovic Lhermitte Arnaud Petit Katell Michaux Charlotte Jung Catherine Chassagne-Clement Vahid Asnafi Yves Bertrand Nathalie Garnier Elizabeth Macintyre |
| author_facet | Amélie Trinquand Adriana Plesa Chrystelle Abdo Fabien Subtil Nathalie Aladjidi Charlotte Rigaud Aurore Touzart Ludovic Lhermitte Arnaud Petit Katell Michaux Charlotte Jung Catherine Chassagne-Clement Vahid Asnafi Yves Bertrand Nathalie Garnier Elizabeth Macintyre |
| author_sort | Amélie Trinquand |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T18:06:56Z |
| format | Article |
| id | doaj.art-cb0a327f9f8945edaa8b8bcc137146b5 |
| institution | Directory Open Access Journal |
| issn | 2572-9241 |
| language | English |
| last_indexed | 2024-03-07T18:06:56Z |
| publishDate | 2021-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | HemaSphere |
| spelling | doaj.art-cb0a327f9f8945edaa8b8bcc137146b52024-03-02T08:54:38ZengWileyHemaSphere2572-92412021-10-01510e64110.1097/HS9.0000000000000641202110000-00002Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 StatusAmélie Trinquand0Adriana Plesa1Chrystelle Abdo2Fabien Subtil3Nathalie Aladjidi4Charlotte Rigaud5Aurore Touzart6Ludovic Lhermitte7Arnaud Petit8Katell Michaux9Charlotte Jung10Catherine Chassagne-Clement11Vahid Asnafi12Yves Bertrand13Nathalie Garnier14Elizabeth Macintyre151 Université de Paris and Institut Necker-Enfants Malades, Laboratoire d’Onco-Hématologie, AP-HP Hôpital Necker-Enfants Malades, Paris, France3 Laboratoire d’Hématologie, Hospices Civiles de Lyon, France1 Université de Paris and Institut Necker-Enfants Malades, Laboratoire d’Onco-Hématologie, AP-HP Hôpital Necker-Enfants Malades, Paris, France4 Service de Biostatistiques des Hospices Civiles de Lyon, France5 Unité d’Hématologie et Cancérologie pédiatrique/CEREVANCE, CHU Bordeaux, France6 Oncologie Pédiatrique, Institut Gustave Roussy, Villejuif, France1 Université de Paris and Institut Necker-Enfants Malades, Laboratoire d’Onco-Hématologie, AP-HP Hôpital Necker-Enfants Malades, Paris, France1 Université de Paris and Institut Necker-Enfants Malades, Laboratoire d’Onco-Hématologie, AP-HP Hôpital Necker-Enfants Malades, Paris, France7 Service d’Hématologie et d’Oncologie pédiatrique, AP-HP, Hôpital Armand Trousseau, Sorbonne Université, Paris, France8 Institut d’Hématologie et d’Oncologie Pédiatrique, Hospices Civiles de Lyon, France8 Institut d’Hématologie et d’Oncologie Pédiatrique, Hospices Civiles de Lyon, France9 Département de Biopathologie, Centre Leon Berard, Lyon, France1 Université de Paris and Institut Necker-Enfants Malades, Laboratoire d’Onco-Hématologie, AP-HP Hôpital Necker-Enfants Malades, Paris, France8 Institut d’Hématologie et d’Oncologie Pédiatrique, Hospices Civiles de Lyon, France8 Institut d’Hématologie et d’Oncologie Pédiatrique, Hospices Civiles de Lyon, France1 Université de Paris and Institut Necker-Enfants Malades, Laboratoire d’Onco-Hématologie, AP-HP Hôpital Necker-Enfants Malades, Paris, FranceWhile 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.http://journals.lww.com/10.1097/HS9.0000000000000641 |
| spellingShingle | Amélie Trinquand Adriana Plesa Chrystelle Abdo Fabien Subtil Nathalie Aladjidi Charlotte Rigaud Aurore Touzart Ludovic Lhermitte Arnaud Petit Katell Michaux Charlotte Jung Catherine Chassagne-Clement Vahid Asnafi Yves Bertrand Nathalie Garnier Elizabeth Macintyre Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 Status HemaSphere |
| title | Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 Status |
| title_full | Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 Status |
| title_fullStr | Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 Status |
| title_full_unstemmed | Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 Status |
| title_short | Toward Pediatric T Lymphoblastic Lymphoma Stratification Based on Minimal Disseminated Disease and NOTCH1/FBXW7 Status |
| title_sort | toward pediatric t lymphoblastic lymphoma stratification based on minimal disseminated disease and notch1 fbxw7 status |
| url | http://journals.lww.com/10.1097/HS9.0000000000000641 |
| work_keys_str_mv | AT amelietrinquand towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT adrianaplesa towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT chrystelleabdo towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT fabiensubtil towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT nathaliealadjidi towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT charlotterigaud towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT auroretouzart towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT ludoviclhermitte towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT arnaudpetit towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT katellmichaux towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT charlottejung towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT catherinechassagneclement towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT vahidasnafi towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT yvesbertrand towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT nathaliegarnier towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status AT elizabethmacintyre towardpediatrictlymphoblasticlymphomastratificationbasedonminimaldisseminateddiseaseandnotch1fbxw7status |