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

被引：54

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

[1] Sex hormones and metabolic syndrome in children and adolescents [J].

Agirbasli, Mehmet ;

Agaoglu, Nihat Bugra ;

Orak, Nilay ;

Caglioz, Hatice ;

Ocek, Tuba ;

Poci, Nertila ;

Salaj, Ada ;

Maya, Saidi .

METABOLISM-CLINICAL AND EXPERIMENTAL, 2009, 58 (09) :1256-1262

[2] Intermittent Versus Continuous PEG-Asparaginase to Reduce Asparaginase-Associated Toxicities: A NOPHO ALL2008 Randomized Study [J].

Albertsen, Birgitte Klug ;

Grell, Kathrine ;

Abrahamsson, Jonas ;

Lund, Bendik ;

Vettenranta, Kim ;

Jonsson, Olafur G. ;

Frandsen, Thomas L. ;

Wolthers, Benjamin O. ;

Heyman, Mats ;

Schmiegelow, Kjeld .

JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (19) :1638-1646

[3]

Aldoss I, 2013, BLOOD, V122, P3915

[4] Classification of acute pancreatitis-2012: revision of the Atlanta classification and definitions by international consensus [J].

Banks, Peter A. ;

Bollen, Thomas L. ;

Dervenis, Christos ;

Gooszen, Hein G. ;

Johnson, Colin D. ;

Sarr, Michael G. ;

Tsiotos, Gregory G. ;

Vege, Santhi Swaroop .

GUT, 2013, 62 (01) :102-111

[5] Favorable outcome for adolescents with acute lymphoblastic leukemia treated on Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia Consortium Protocols [J].

Barry, Elly ;

DeAngelo, Daniel J. ;

Neuberg, Donna ;

Stevenson, Kristen ;

Loh, Mignon L. ;

Asselin, Barbara L. ;

Barr, Ronald D. ;

Clavell, Luis A. ;

Hurwitz, Craig A. ;

Moghrabi, Albert ;

Samson, Yvan ;

Schorin, Marshall ;

Cohen, Harvey J. ;

Sallan, Stephen E. ;

Silverman, Lewis B. .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (07) :813-819

[6]

BRADLEY EL, 1993, ARCH SURG-CHICAGO, V128, P586

[7] Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia [J].

DeAngelo, D. J. ;

Stevenson, K. E. ;

Dahlberg, S. E. ;

Silverman, L. B. ;

Couban, S. ;

Supko, J. G. ;

Amrein, P. C. ;

Ballen, K. K. ;

Seftel, M. D. ;

Turner, A. R. ;

Leber, B. ;

Howson-Jan, K. ;

Kelly, K. ;

Cohen, S. ;

Matthews, J. H. ;

Savoie, L. ;

Wadleigh, M. ;

Sirulnik, L. A. ;

Galinsky, I. ;

Neuberg, D. S. ;

Sallan, S. E. ;

Stone, R. M. .

LEUKEMIA, 2015, 29 (03) :526-534

[8] Prothrombogenic factors and reduced antioxidative defense in children and adolescents with pre-metabolic and metabolic syndrome [J].

Dimitrijevic-Sreckovic, Vesna ;

Colak, Emina ;

Djordjevic, Predrag ;

Gostiljac, Drasko ;

Sreckovic, Branko ;

Popovic, Srdjan ;

Canovic, Fadil ;

Ilic, Miroijub ;

Obrenovic, Radmila ;

Vukcevic, Vladan ;

Nikolic, Dragan ;

Nisic, Tanja ;

Milic, Gordana ;

Pejcic, Gordana .

CLINICAL CHEMISTRY AND LABORATORY MEDICINE, 2007, 45 (09) :1140-1144

[9] Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies:: results of a randomized European Organisation for Research and Treatment of Cancer -: Children's Leukemia Group phase 3 trial [J].

Duval, M ;

Suciu, S ;

Ferster, A ;

Rialland, X ;

Nelken, B ;

Lutz, P ;

Benoit, Y ;

Robert, A ;

Manel, AM ;

Vilmer, E ;

Otten, J ;

Philippe, N .

BLOOD, 2002, 99 (08) :2734-2739

[10] Access to clinical trials for adolescents with soft tissue sarcomas: Enrollment in European pediatric Soft tissue sarcoma Study Group (EpSSG) protocols [J].

Ferrari, Andrea ;

Trama, Annalisa ;

De Paoli, Angela ;

Bergeron, Christophe ;

Merks, Johannes H. M. ;

Jenney, Meriel ;

Orbach, Daniel ;

Chisholm, Julia C. ;

Gallego, Soledad ;

Glosli, Heidi ;

De Salvo, Gian Luca ;

Botta, Laura ;

Gatta, Gemma ;

Bisogno, Gianni .

PEDIATRIC BLOOD & CANCER, 2017, 64 (06)

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