Refining risk stratification in paediatric B-acute lymphoblastic leukaemia : Combining IKZF1plus and Day 15 MRD positivity
© 2024 British Society for Haematology and John Wiley & Sons Ltd..
This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus. Both IKZF1 deletion (14.6%) and IKZF1plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:204 |
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| Enthalten in: |
British journal of haematology - 204(2024), 4 vom: 01. Apr., Seite 1344-1353 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Hsi-Che [VerfasserIn] |
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| Links: |
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| Themen: |
148971-36-2 |
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| Anmerkungen: |
Date Completed 11.04.2024 Date Revised 16.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/bjh.19338 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369691350 |
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| 245 | 1 | 0 | |a Refining risk stratification in paediatric B-acute lymphoblastic leukaemia |b Combining IKZF1plus and Day 15 MRD positivity |
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| 520 | |a © 2024 British Society for Haematology and John Wiley & Sons Ltd. | ||
| 520 | |a This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus. Both IKZF1 deletion (14.6%) and IKZF1plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Jaing, Tang-Her |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Kang-Hsi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shih-Hsiang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Shih-Chung |e verfasserin |4 aut | |
| 700 | 1 | |a Yeh, Ting-Chi |e verfasserin |4 aut | |
| 700 | 1 | |a Hsiao, Chih-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Te-Kau |e verfasserin |4 aut | |
| 700 | 1 | |a Yen, Hsiu-Ju |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Fang-Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Pei-Chin |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Jen-Yin |e verfasserin |4 aut | |
| 700 | 1 | |a Sheen, Jiunn-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Liao, Yu-Mei |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Tsung-Yen |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yu-Chieh |e verfasserin |4 aut | |
| 700 | 1 | |a Chiou, Shyh-Shin |e verfasserin |4 aut | |
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| 700 | 1 | |a Pui, Ching-Hon |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Der-Cherng |e verfasserin |4 aut | |
| 700 | 1 | |a Shih, Lee-Yung |e verfasserin |4 aut | |
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