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Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia: Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age

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Rank, CU, Wolthers, BO, Grell, K, Albertsen, BK, Frandsen, TL, Overgaard, UM, Toft, N, Nielsen, OJ, Wehner, PS, Harila-Saari, A, Heyman, MM, Malmros, J, Abrahamsson, J, Norén-Nyström, U, Tomaszewska-Toporska, B, Lund, B, Jarvis, KB, Quist-Paulsen, P, Vaitkevičienė, GE, Griškevičius, L, Taskinen, M, Wartiovaara-Kautto, U, Lepik, K, Punab, M, Jónsson, ÓG & Schmiegelow, K 2020, 'Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia: Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age' Journal of clinical oncology : official journal of the American Society of Clinical Oncology, bind 38, nr. 2, s. 145-154. https://doi.org/10.1200/JCO.19.02208

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Rank CU, Wolthers BO, Grell K, Albertsen BK, Frandsen TL, Overgaard UM, Toft N, Nielsen OJ, Wehner PS, Harila-Saari A, Heyman MM, Malmros J, Abrahamsson J, Norén-Nyström U, Tomaszewska-Toporska B, Lund B, Jarvis KB, Quist-Paulsen P, Vaitkevičienė GE, Griškevičius L, Taskinen M, Wartiovaara-Kautto U, Lepik K, Punab M, Jónsson ÓG, Schmiegelow K. 2020. Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia: Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 38(2):145-154. https://doi.org/10.1200/JCO.19.02208

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Author

Rank, Cecilie U ; Wolthers, Benjamin O ; Grell, Kathrine ; Albertsen, Birgitte K ; Frandsen, Thomas L ; Overgaard, Ulrik M ; Toft, Nina ; Nielsen, Ove J ; Wehner, Peder S ; Harila-Saari, Arja ; Heyman, Mats M ; Malmros, Johan ; Abrahamsson, Jonas ; Norén-Nyström, Ulrika ; Tomaszewska-Toporska, Beata ; Lund, Bendik ; Jarvis, Kirsten B ; Quist-Paulsen, Petter ; Vaitkevičienė, Goda E ; Griškevičius, Laimonas ; Taskinen, Mervi ; Wartiovaara-Kautto, Ulla ; Lepik, Kristi ; Punab, Mari ; Jónsson, Ólafur G ; Schmiegelow, Kjeld. / Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia : Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age. I: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020 ; Bind 38, Nr. 2. s. 145-154.

Bibtex

@article{d5fa540a498a4b738e3fcf370b7a8bb0,
title = "Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia: Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age",
abstract = "PURPOSE: Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored.PATIENTS AND METHODS: We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.RESULTS: Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95{\%} CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0{\%} for children (1.0-9.9 years: 95{\%} CI, 5.4 to 8.6), 10.1{\%} for adolescents (10.0 to 17.9 years: 95{\%} CI, 7.0 to 13.3), and 11.0{\%} for adults (18.0-45.9 years: 95{\%} CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95{\%} CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95{\%} CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95{\%} CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse.CONCLUSION: Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.",
author = "Rank, {Cecilie U} and Wolthers, {Benjamin O} and Kathrine Grell and Albertsen, {Birgitte K} and Frandsen, {Thomas L} and Overgaard, {Ulrik M} and Nina Toft and Nielsen, {Ove J} and Wehner, {Peder S} and Arja Harila-Saari and Heyman, {Mats M} and Johan Malmros and Jonas Abrahamsson and Ulrika Nor{\'e}n-Nystr{\"o}m and Beata Tomaszewska-Toporska and Bendik Lund and Jarvis, {Kirsten B} and Petter Quist-Paulsen and Vaitkevičienė, {Goda E} and Laimonas Griškevičius and Mervi Taskinen and Ulla Wartiovaara-Kautto and Kristi Lepik and Mari Punab and J{\'o}nsson, {{\'O}lafur G} and Kjeld Schmiegelow",
year = "2020",
month = "1",
day = "1",
doi = "10.1200/JCO.19.02208",
language = "English",
volume = "38",
pages = "145--154",
journal = "Molecular and Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "2",

}

RIS

TY - JOUR

T1 - Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia

T2 - Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age

AU - Rank, Cecilie U

AU - Wolthers, Benjamin O

AU - Grell, Kathrine

AU - Albertsen, Birgitte K

AU - Frandsen, Thomas L

AU - Overgaard, Ulrik M

AU - Toft, Nina

AU - Nielsen, Ove J

AU - Wehner, Peder S

AU - Harila-Saari, Arja

AU - Heyman, Mats M

AU - Malmros, Johan

AU - Abrahamsson, Jonas

AU - Norén-Nyström, Ulrika

AU - Tomaszewska-Toporska, Beata

AU - Lund, Bendik

AU - Jarvis, Kirsten B

AU - Quist-Paulsen, Petter

AU - Vaitkevičienė, Goda E

AU - Griškevičius, Laimonas

AU - Taskinen, Mervi

AU - Wartiovaara-Kautto, Ulla

AU - Lepik, Kristi

AU - Punab, Mari

AU - Jónsson, Ólafur G

AU - Schmiegelow, Kjeld

PY - 2020/1/1

Y1 - 2020/1/1

N2 - PURPOSE: Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored.PATIENTS AND METHODS: We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.RESULTS: Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse.CONCLUSION: Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.

AB - PURPOSE: Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored.PATIENTS AND METHODS: We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.RESULTS: Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse.CONCLUSION: Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.

U2 - 10.1200/JCO.19.02208

DO - 10.1200/JCO.19.02208

M3 - Journal article

VL - 38

SP - 145

EP - 154

JO - Molecular and Clinical Oncology

JF - Molecular and Clinical Oncology

SN - 0732-183X

IS - 2

ER -

ID: 58919036