Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol

Nina Toft; Henrik Birgens; Jonas Abrahamsson; Per Bernell; Laimonas Griškevi?ius; Helene Hallböök; Mats Heyman; Mette Skov Holm; Erik Hulegårdh; Tobias Wirenfeldt Klausen; Hanne V Marquart; Olafur Gísli Jónsson; Ove Juul Nielsen; Petter Quist-Paulsen; Mervi Taskinen; Goda Vaitkeviciene; Kim Vettenranta; Ann Åsberg; Kjeld Schmiegelow

doi:10.1111/ejh.12097

Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol

Nina Toft, Henrik Birgens, Jonas Abrahamsson, Per Bernell, Laimonas Griškevi?ius, Helene Hallböök, Mats Heyman, Mette Skov Holm, Erik Hulegårdh, Tobias Wirenfeldt Klausen, Hanne V Marquart, Olafur Gísli Jónsson, Ove Juul Nielsen, Petter Quist-Paulsen, Mervi Taskinen, Goda Vaitkeviciene, Kim Vettenranta, Ann Åsberg, Kjeld Schmiegelow

Department of Clinical Medicine

93 Citations (Scopus)

Abstract

Background: The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined. Design and methods: We analyzed 749 patients aged 1-45 yr treated by the NOPHO ALL-2008 protocol. Minimal residual disease (MRD) on days 29 and 79, immunophenotype, white blood cell count (WBC), and cytogenetics were used to stratify patients to standard-, intermediate-, or high-risk treatment with or without hematopoietic stem cell transplantation. Results: Adults aged 18-45 had significantly lower WBCs at diagnosis compared with children aged 1-9 and 10-17 yr, but significantly more adults were stratified to high-risk chemotherapy (8%, 14%, 17%; P < 0.0001) or high-risk chemotherapy with transplantation (4%, 13%, 19%; P < 0.0001). This age-dependent skewing of risk grouping reflected more T-ALL (11%, 27%, 33%, P < 0.0001), poorer MRD response day 29 (MRD < 0.1%: 75%, 61%, 52%; P < 0.0001), and more MLL gene rearrangements (3%, 3%, 10%; P = 0.005) in older patients. Conclusions: Even if identical diagnostics, treatment, and risk stratification are implemented, more adults will be stratified to high-risk therapy, which should be considered when comparing pediatric and adult outcomes.

Original language	English
Journal	European Journal of Haematology
Volume	90
Issue number	5
Pages (from-to)	404-412
Number of pages	9
ISSN	0902-4441
DOIs	https://doi.org/10.1111/ejh.12097
Publication status	Published - May 2013

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Toft, N., Birgens, H., Abrahamsson, J., Bernell, P., Griškevi?ius, L., Hallböök, H., Heyman, M., Holm, M. S., Hulegårdh, E., Klausen, T. W., Marquart, H. V., Jónsson, O. G., Nielsen, O. J., Quist-Paulsen, P., Taskinen, M., Vaitkeviciene, G., Vettenranta, K., Åsberg, A., & Schmiegelow, K. (2013). Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol. European Journal of Haematology, 90(5), 404-412. https://doi.org/10.1111/ejh.12097

Toft, N, Birgens, H, Abrahamsson, J, Bernell, P, Griškevi?ius, L, Hallböök, H, Heyman, M, Holm, MS, Hulegårdh, E, Klausen, TW, Marquart, HV, Jónsson, OG, Nielsen, OJ, Quist-Paulsen, P, Taskinen, M, Vaitkeviciene, G, Vettenranta, K, Åsberg, A & Schmiegelow, K 2013, 'Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol', European Journal of Haematology, vol. 90, no. 5, pp. 404-412. https://doi.org/10.1111/ejh.12097

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title = "Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol",

abstract = "Background: The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined. Design and methods: We analyzed 749 patients aged 1-45 yr treated by the NOPHO ALL-2008 protocol. Minimal residual disease (MRD) on days 29 and 79, immunophenotype, white blood cell count (WBC), and cytogenetics were used to stratify patients to standard-, intermediate-, or high-risk treatment with or without hematopoietic stem cell transplantation. Results: Adults aged 18-45 had significantly lower WBCs at diagnosis compared with children aged 1-9 and 10-17 yr, but significantly more adults were stratified to high-risk chemotherapy (8%, 14%, 17%; P < 0.0001) or high-risk chemotherapy with transplantation (4%, 13%, 19%; P < 0.0001). This age-dependent skewing of risk grouping reflected more T-ALL (11%, 27%, 33%, P < 0.0001), poorer MRD response day 29 (MRD < 0.1%: 75%, 61%, 52%; P < 0.0001), and more MLL gene rearrangements (3%, 3%, 10%; P = 0.005) in older patients. Conclusions: Even if identical diagnostics, treatment, and risk stratification are implemented, more adults will be stratified to high-risk therapy, which should be considered when comparing pediatric and adult outcomes.",

author = "Nina Toft and Henrik Birgens and Jonas Abrahamsson and Per Bernell and Laimonas Gri{\v s}kevi?ius and Helene Hallb{\"o}{\"o}k and Mats Heyman and Holm, {Mette Skov} and Erik Huleg{\aa}rdh and Klausen, {Tobias Wirenfeldt} and Marquart, {Hanne V} and J{\'o}nsson, {Olafur G{\'i}sli} and Nielsen, {Ove Juul} and Petter Quist-Paulsen and Mervi Taskinen and Goda Vaitkeviciene and Kim Vettenranta and Ann {\AA}sberg and Kjeld Schmiegelow",

year = "2013",

month = may,

doi = "10.1111/ejh.12097",

language = "English",

volume = "90",

pages = "404--412",

journal = "European Journal of Haematology",

issn = "0902-4441",

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TY - JOUR

T1 - Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol

AU - Toft, Nina

AU - Birgens, Henrik

AU - Abrahamsson, Jonas

AU - Bernell, Per

AU - Griškevi?ius, Laimonas

AU - Hallböök, Helene

AU - Heyman, Mats

AU - Holm, Mette Skov

AU - Hulegårdh, Erik

AU - Klausen, Tobias Wirenfeldt

AU - Marquart, Hanne V

AU - Jónsson, Olafur Gísli

AU - Nielsen, Ove Juul

AU - Quist-Paulsen, Petter

AU - Taskinen, Mervi

AU - Vaitkeviciene, Goda

AU - Vettenranta, Kim

AU - Åsberg, Ann

AU - Schmiegelow, Kjeld

PY - 2013/5

Y1 - 2013/5

N2 - Background: The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined. Design and methods: We analyzed 749 patients aged 1-45 yr treated by the NOPHO ALL-2008 protocol. Minimal residual disease (MRD) on days 29 and 79, immunophenotype, white blood cell count (WBC), and cytogenetics were used to stratify patients to standard-, intermediate-, or high-risk treatment with or without hematopoietic stem cell transplantation. Results: Adults aged 18-45 had significantly lower WBCs at diagnosis compared with children aged 1-9 and 10-17 yr, but significantly more adults were stratified to high-risk chemotherapy (8%, 14%, 17%; P < 0.0001) or high-risk chemotherapy with transplantation (4%, 13%, 19%; P < 0.0001). This age-dependent skewing of risk grouping reflected more T-ALL (11%, 27%, 33%, P < 0.0001), poorer MRD response day 29 (MRD < 0.1%: 75%, 61%, 52%; P < 0.0001), and more MLL gene rearrangements (3%, 3%, 10%; P = 0.005) in older patients. Conclusions: Even if identical diagnostics, treatment, and risk stratification are implemented, more adults will be stratified to high-risk therapy, which should be considered when comparing pediatric and adult outcomes.

AB - Background: The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined. Design and methods: We analyzed 749 patients aged 1-45 yr treated by the NOPHO ALL-2008 protocol. Minimal residual disease (MRD) on days 29 and 79, immunophenotype, white blood cell count (WBC), and cytogenetics were used to stratify patients to standard-, intermediate-, or high-risk treatment with or without hematopoietic stem cell transplantation. Results: Adults aged 18-45 had significantly lower WBCs at diagnosis compared with children aged 1-9 and 10-17 yr, but significantly more adults were stratified to high-risk chemotherapy (8%, 14%, 17%; P < 0.0001) or high-risk chemotherapy with transplantation (4%, 13%, 19%; P < 0.0001). This age-dependent skewing of risk grouping reflected more T-ALL (11%, 27%, 33%, P < 0.0001), poorer MRD response day 29 (MRD < 0.1%: 75%, 61%, 52%; P < 0.0001), and more MLL gene rearrangements (3%, 3%, 10%; P = 0.005) in older patients. Conclusions: Even if identical diagnostics, treatment, and risk stratification are implemented, more adults will be stratified to high-risk therapy, which should be considered when comparing pediatric and adult outcomes.

U2 - 10.1111/ejh.12097

DO - 10.1111/ejh.12097

M3 - Journal article

C2 - 23461707

SN - 0902-4441

VL - 90

SP - 404

EP - 412

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 5

ER -

Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol

Abstract

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