Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion

Anthony V. Moorman; Claire Schwab; Emily Winterman; Jerry Hancock; Anna Castleton; Michelle Cummins; Brenda Gibson; Nick Goulden; Pam Kearns; Beki James; Amy A. Kirkwood; Donna Lancaster; Mabrouk Madi; Andrew McMillan; Jayashree Motwani; Alice Norton; Aengus O’Marcaigh; Katharine Patrick; Neha Bhatnagar; Amrana Qureshi; Deborah Richardson; Simone Stokley; Gordon Taylor; Frederik W. Delft; John Moppett; Christine J. Harrison; Sujith Samarasinghe; Ajay Vora

doi:10.1111/bjh.17093

Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion

Anthony V. Moorman, Claire Schwab, Emily Winterman, Jerry Hancock, Anna Castleton, Michelle Cummins, Brenda Gibson, Nick Goulden, Pam Kearns, Beki James, Amy A. Kirkwood, Donna Lancaster, Mabrouk Madi, Andrew McMillan, Jayashree Motwani, Alice Norton, Aengus O’Marcaigh, Katharine Patrick, Neha Bhatnagar, Amrana QureshiDeborah Richardson, Simone Stokley, Gordon Taylor, Frederik W. Delft, John Moppett, Christine J. Harrison, Sujith Samarasinghe, Ajay Vora

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Patients with an ABL-class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post-induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL-class patients who did and did not receive a TKI in first remission to be compared. ABL-class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009).

Original language	English
Pages (from-to)	844-851
Number of pages	8
Journal	British Journal of Haematology
Volume	191
Issue number	5
Early online date	14 Sept 2020
DOIs	https://doi.org/10.1111/bjh.17093
Publication status	Published - 14 Dec 2020

Bibliographical note

Funding Information:
We would like thank all the patients who took part in this study as well as their families. We acknowledge Blood Cancer UK (formerly Bloodwise) for financial support and the member laboratories of the UK Cancer Cytogenetic Group (UKCCG) for providing cytogenetic data and material; in particular Gavin Cuthbert at the Northern Genetics Service (Newcastle upon Tyne Hospitals NHS Trust) for additional genomic analyses. We acknowledge the input of all the scientists and technicians working in the MRD laboratories: Bristol Genetics Laboratory, Southmead Hospital, Bristol; Molecular Biology Laboratory, Royal Hospital for Sick Children, Glasgow; Molecular Haematology Laboratory, Royal London Hospital, London; and the Molecular Genetics Service, Sheffield Children?s Hospital, Sheffield. Primary childhood leukaemia samples used in this study were provided by the Blood Cancer UK Childhood Leukaemia Cell Bank working with the aforementioned MRD laboratories.

Publisher Copyright:
© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

Keywords

ABL-class fusion
paediatric acute lymphoblastic leukaemia
prognostic factors
targeted therapy
tyrosine kinase inhibitor

ASJC Scopus subject areas

Hematology

Access to Document

10.1111/bjh.17093

Cite this

Moorman, A. V., Schwab, C., Winterman, E., Hancock, J., Castleton, A., Cummins, M., Gibson, B., Goulden, N., Kearns, P., James, B., Kirkwood, A. A., Lancaster, D., Madi, M., McMillan, A., Motwani, J., Norton, A., O’Marcaigh, A., Patrick, K., Bhatnagar, N., ... Vora, A. (2020). Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion. British Journal of Haematology, 191(5), 844-851. https://doi.org/10.1111/bjh.17093

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title = "Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion",

abstract = "Patients with an ABL-class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post-induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL-class patients who did and did not receive a TKI in first remission to be compared. ABL-class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009).",

keywords = "ABL-class fusion, paediatric acute lymphoblastic leukaemia, prognostic factors, targeted therapy, tyrosine kinase inhibitor",

author = "Moorman, {Anthony V.} and Claire Schwab and Emily Winterman and Jerry Hancock and Anna Castleton and Michelle Cummins and Brenda Gibson and Nick Goulden and Pam Kearns and Beki James and Kirkwood, {Amy A.} and Donna Lancaster and Mabrouk Madi and Andrew McMillan and Jayashree Motwani and Alice Norton and Aengus O{\textquoteright}Marcaigh and Katharine Patrick and Neha Bhatnagar and Amrana Qureshi and Deborah Richardson and Simone Stokley and Gordon Taylor and Delft, {Frederik W.} and John Moppett and Harrison, {Christine J.} and Sujith Samarasinghe and Ajay Vora",

note = "Funding Information: We would like thank all the patients who took part in this study as well as their families. We acknowledge Blood Cancer UK (formerly Bloodwise) for financial support and the member laboratories of the UK Cancer Cytogenetic Group (UKCCG) for providing cytogenetic data and material; in particular Gavin Cuthbert at the Northern Genetics Service (Newcastle upon Tyne Hospitals NHS Trust) for additional genomic analyses. We acknowledge the input of all the scientists and technicians working in the MRD laboratories: Bristol Genetics Laboratory, Southmead Hospital, Bristol; Molecular Biology Laboratory, Royal Hospital for Sick Children, Glasgow; Molecular Haematology Laboratory, Royal London Hospital, London; and the Molecular Genetics Service, Sheffield Children?s Hospital, Sheffield. Primary childhood leukaemia samples used in this study were provided by the Blood Cancer UK Childhood Leukaemia Cell Bank working with the aforementioned MRD laboratories. Publisher Copyright: {\textcopyright} 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.",

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month = dec,

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doi = "10.1111/bjh.17093",

language = "English",

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Moorman, AV, Schwab, C, Winterman, E, Hancock, J, Castleton, A, Cummins, M, Gibson, B, Goulden, N, Kearns, P, James, B, Kirkwood, AA, Lancaster, D, Madi, M, McMillan, A, Motwani, J, Norton, A, O’Marcaigh, A, Patrick, K, Bhatnagar, N, Qureshi, A, Richardson, D, Stokley, S, Taylor, G, Delft, FW, Moppett, J, Harrison, CJ, Samarasinghe, S & Vora, A 2020, 'Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion', British Journal of Haematology, vol. 191, no. 5, pp. 844-851. https://doi.org/10.1111/bjh.17093

TY - JOUR

T1 - Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion

AU - Moorman, Anthony V.

AU - Schwab, Claire

AU - Winterman, Emily

AU - Hancock, Jerry

AU - Castleton, Anna

AU - Cummins, Michelle

AU - Gibson, Brenda

AU - Goulden, Nick

AU - Kearns, Pam

AU - James, Beki

AU - Kirkwood, Amy A.

AU - Lancaster, Donna

AU - Madi, Mabrouk

AU - McMillan, Andrew

AU - Motwani, Jayashree

AU - Norton, Alice

AU - O’Marcaigh, Aengus

AU - Patrick, Katharine

AU - Bhatnagar, Neha

AU - Qureshi, Amrana

AU - Richardson, Deborah

AU - Stokley, Simone

AU - Taylor, Gordon

AU - Delft, Frederik W.

AU - Moppett, John

AU - Harrison, Christine J.

AU - Samarasinghe, Sujith

AU - Vora, Ajay

N1 - Funding Information: We would like thank all the patients who took part in this study as well as their families. We acknowledge Blood Cancer UK (formerly Bloodwise) for financial support and the member laboratories of the UK Cancer Cytogenetic Group (UKCCG) for providing cytogenetic data and material; in particular Gavin Cuthbert at the Northern Genetics Service (Newcastle upon Tyne Hospitals NHS Trust) for additional genomic analyses. We acknowledge the input of all the scientists and technicians working in the MRD laboratories: Bristol Genetics Laboratory, Southmead Hospital, Bristol; Molecular Biology Laboratory, Royal Hospital for Sick Children, Glasgow; Molecular Haematology Laboratory, Royal London Hospital, London; and the Molecular Genetics Service, Sheffield Children?s Hospital, Sheffield. Primary childhood leukaemia samples used in this study were provided by the Blood Cancer UK Childhood Leukaemia Cell Bank working with the aforementioned MRD laboratories. Publisher Copyright: © 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.

PY - 2020/12/14

Y1 - 2020/12/14

N2 - Patients with an ABL-class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post-induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL-class patients who did and did not receive a TKI in first remission to be compared. ABL-class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009).

AB - Patients with an ABL-class fusion have a high risk of relapse on standard chemotherapy but are sensitive to tyrosine kinase inhibitors (TKI). In UKALL2011, we screened patients with post-induction MRD ≥1% and positive patients (12%) received adjuvant TKI. As the intervention started during UKALL2011, not all eligible patients were screened prospectively. Retrospective screening of eligible patients allowed the outcome of equivalent ABL-class patients who did and did not receive a TKI in first remission to be compared. ABL-class patients who received a TKI in first remission had a reduced risk of relapse/refractory disease: 0% vs. 63% at four years (P = 0·009).

KW - ABL-class fusion

KW - paediatric acute lymphoblastic leukaemia

KW - prognostic factors

KW - targeted therapy

KW - tyrosine kinase inhibitor

UR - https://doi.org/10.1111/bjh.17093

U2 - 10.1111/bjh.17093

DO - 10.1111/bjh.17093

M3 - Article

SN - 0007-1048

VL - 191

SP - 844

EP - 851

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 5

ER -

Adjuvant tyrosine kinase inhibitor therapy improves outcome for children and adolescents with acute lymphoblastic leukaemia who have an ABL‐class fusion

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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