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

被引：57

作者：

Rank, Cecilie U. ^{[1
,2
]}

Wolthers, Benjamin O. ^{[1
]}

Grell, Kathrine ^{[1
,2
]}

Albertsen, Birgitte K. ^{[3
]}

Frandsen, Thomas L. ^{[1
]}

Overgaard, Ulrik M. ^{[1
]}

Toft, Nina ^{[4
]}

Nielsen, Ove J. ^{[1
]}

Wehner, Peder S. ^{[5
]}

Harila-Saari, Arja ^{[6
]}

Heyman, Mats M. ^{[7
]}

Malmros, Johan ^{[7
]}

Abrahamsson, Jonas ^{[8
]}

Noren-Nystrom, Ulrika ^{[9
]}

Tomaszewska-Toporska, Beata ^{[10
]}

Lund, Bendik ^{[11
]}

Jarvis, Kirsten B. ^{[12
,13
]}

Quist-Paulsen, Petter ^{[11
]}

Vaitkeviciene, Goda E. ^{[14
,15
]}

Griskevicius, Laimonas ^{[14
,15
]}

Taskinen, Mervi ^{[16
]}

Wartiovaara-Kautto, Ulla ^{[16
]}

Lepik, Kristi ^{[17
]}

Punab, Mari ^{[18
]}

Jonsson, Olafur G. ^{[19
]}

Schmiegelow, Kjeld ^{[1
,2
]}

机构：

[1] Rigshosp, Copenhagen, Denmark

[2] Univ Copenhagen, Copenhagen, Denmark

[3] Aarhus Univ Hosp, Aarhus, Denmark

[4] Herlev Univ Hosp, Herlev, Denmark

[5] Odense Univ Hosp, Odense, Denmark

[6] Uppsala Univ Hosp, Uppsala, Sweden

[7] Karolinska Univ Hosp, Stockholm, Sweden

[8] Queen Silvia Childrens Hosp, Gothenburg, Sweden

[9] Umea Univ, Umea, Sweden

[10] Skane Univ Hosp, Lund, Sweden

[11] Trondheim Reg & Univ Hosp, Trondheim, Norway

[12] Oslo Univ Hosp, Oslo, Norway

[13] Univ Oslo, Oslo, Norway

[14] Vilnius Univ, Hosp Santaros Klin, Vilnius, Lithuania

[15] Vilnius Univ, Vilnius, Lithuania

[16] Helsinki Univ Hosp, Helsinki, Finland

[17] Tallinn Childrens Hosp, Tallinn, Estonia

[18] Tartu Univ Hosp, Tartu, Estonia

[19] Reykjavik Univ Hosp, Reykjavik, Iceland

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2020年 / 38卷 / 02期

关键词：

FARBER-CANCER-INSTITUTE; COLI L-ASPARAGINASE; ERWINIA-ASPARAGINASE; STANDARD-RISK; YOUNG-ADULTS; CHILDREN; ADOLESCENTS; PROTOCOL; CLASSIFICATION; DEFINITIONS;

D O I：

10.1200/JCO.19.02208

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2019 by American Society of Clinical Oncology

引用

页码：145 / +

页数：11

共 45 条

[41] Postinduction Dexamethasone and Individualized Dosing of Escherichia Coli L-Asparaginase Each Improve Outcome of Children and Adolescents With Newly Diagnosed Acute Lymphoblastic Leukemia: Results From a Randomized Study-Dana-Farber Cancer Institute ALL Consortium Protocol 00-01 [J].

Vrooman, Lynda M. ;

Stevenson, Kristen E. ;

Supko, Jeffrey G. ;

O'Brien, Jane ;

Dahlberg, Suzanne E. ;

Asselin, Barbara L. ;

Athale, Uma H. ;

Clavell, Luis A. ;

Kelly, Kara M. ;

Kutok, Jeffery L. ;

Laverdiere, Caroline ;

Lipshultz, Steven E. ;

Michon, Bruno ;

Schorin, Marshall ;

Relling, Mary V. ;

Cohen, Harvey J. ;

Neuberg, Donna S. ;

Sallan, Stephen E. ;

Silverman, Lewis B. .

JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (09) :1202-1210

[42] Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol [J].

Wolthers, B. O. ;

Frandsen, T. L. ;

Abrahamsson, J. ;

Albertsen, B. K. ;

Helt, L. R. ;

Heyman, M. ;

Jonsson, O. G. ;

Korgvee, L. T. ;

Lund, B. ;

Raja, R. A. ;

Rasmussen, K. K. ;

Taskinen, M. ;

Tulstrup, M. ;

Vaitkeviciene, G. E. ;

Yadav, R. ;

Gupta, R. ;

Schmiegelow, K. .

LEUKEMIA, 2017, 31 (02) :325-332

[43] Trypsin-encoding PRSS1-PRSS2 variations influence the risk of asparaginase-associated pancreatitis in children with acute lymphoblastic leukemia: a Ponte di Legno toxicity working group report [J].

Wolthers, Benjamin O. ;

Frandsen, Thomas L. ;

Patel, Chirag J. ;

Abaji, Rachid ;

Attarbaschi, Andishe ;

Barzilai, Shlomit ;

Colombini, Antonella ;

Escherich, Gabriele ;

Grosjean, Marie ;

Krajinovic, Maja ;

Larsen, Eric ;

Liang, Der-Cherng ;

Moericke, Anja ;

Rasmussen, Kirsten K. ;

Samarasinghe, Sujith ;

Silverman, Lewis B. ;

van der Sluis, Inge M. ;

Stanulla, Martin ;

Tulstrup, Morten ;

Yadav, Rachita ;

Yang, Wenjian ;

Zapotocka, Ester ;

Gupta, Ramneek ;

Schmiegelow, Kjeld .

HAEMATOLOGICA, 2019, 104 (03) :556-563

[44] Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study [J].

Wolthers, Benjamin O. ;

Frandsen, Thomas L. ;

Baruchel, Andre ;

Attarbaschi, Andishe ;

Barzilai, Shlomit ;

Colombini, Antonella ;

Escherich, Gabriele ;

Grell, Kathrine ;

Inaba, Hiroto ;

Kovacs, Gabor ;

Liang, Der-Cherng ;

Mateos, Marion ;

Mondelaers, Veerle ;

Moericke, Anja ;

Ociepa, Tomasz ;

Samarasinghe, Sujith ;

Silverman, Lewis B. ;

van der Sluis, Inge M. ;

Stanulla, Martin ;

Vrooman, Lynda M. ;

Yano, Michihiro ;

Zapotocka, Ester ;

Schmiegelow, Kjeld .

LANCET ONCOLOGY, 2017, 18 (09) :1238-1248

[45] Insulin-dependent diabetes: A chronic complication to acute pancreatitis in childhood acute lymphoblastic leukemia [J].

Wolthers, Benjamin Ole ;

Mogensen, Pernille R. ;

Frandsen, Thomas L. ;

Abrahamsson, Jonas ;

Behrendtz, Mikael ;

Heyman, Mats ;

Lohi, Olli ;

Noren-Nystroem, Ulrika ;

Ruud, Ellen ;

Schmiegelow, Kjeld .

PEDIATRIC BLOOD & CANCER, 2019, 66 (01)

← 1 2 3 4 5 →