World Journal of Emergency Medicine ›› 2022, Vol. 13 ›› Issue (4): 313-321.doi: 10.5847/wjem.j.1920-8642.2022.062
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Chen-xi Liu1, Yun-yu Zhang2, Qiu-shi Yang2, Shu-hong Shen1, Jing Chen1, Yan-jing Tang1, Chang-cheng Chen1, Zhuo Wang1, Bi-ru Li2, Juan Qian2, Ying Wang2(
), Wen-ting Hu1(), Bo-tao Ning2()
Received:2021-11-29
Accepted:2022-02-20
Online:2022-06-23
Published:2022-07-01
Contact:
Ying Wang,Wen-ting Hu,Bo-tao Ning
E-mail:ywang_picu@shsmu.edu.cn;huwenting@scmc.com.cn;ningbotao@126.com
Chen-xi Liu, Yun-yu Zhang, Qiu-shi Yang, Shu-hong Shen, Jing Chen, Yan-jing Tang, Chang-cheng Chen, Zhuo Wang, Bi-ru Li, Juan Qian, Ying Wang, Wen-ting Hu, Bo-tao Ning. Asparaginase-associated pancreatitis in chemotherapy- treated pediatric patients: a five-year retrospective study[J]. World Journal of Emergency Medicine, 2022, 13(4): 313-321.
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URL: http://wjem.com.cn/EN/10.5847/wjem.j.1920-8642.2022.062
Table 1.
Baseline and underlying disease characteristics
| Characteristics | Patients with AAP (%) |
|---|---|
| Age, years (n=49) | |
| <5 | 15 (30.6) |
| 5-9.9 | 15 (30.6) |
| ≥10 | 19 (38.8) |
| Sex (n=49) | |
| Male | 33 (67.3) |
| Female | 16 (32.7) |
| Underlying disease (n=49) | |
| ALL | 44 (89.8) |
| PTCL | 1 (2.0) |
| TCBL | 1 (2.0) |
| CML-BC | 1 (2.0) |
| Burkitt lymphoma | 1 (2.0) |
| Mixed lineage leukemia | 1 (2.0) |
| Baseline WBC counts (ALL, n=44) | |
| <50×109/L | 34 (77.3) |
| (50-299) ×109/L | 5 (11.4) |
| ≥ 300×109/L | 5 (11.4) |
| Immunophenotype (ALL, n=44) | |
| B-cell | 34 (77.3) |
| T-cell | 10 (22.7) |
| Fusion gene detected (ALL, n=44) | |
| ETV6-RUNX1 | 5 (11.4) |
| Ph+/BCR-ABL | 4 (9.1) |
| TCF3/PBX1 | 2 (4.5) |
| MLL-r | 1 (2.3) |
| No aberrations | 33 (75.0) |
| Risk group (ALL, n=44) | |
| LR | 9 (20.5) |
| IR | 31 (70.5) |
| HR | 4 (9.1) |
| Chemotherapy in cycle (n=49) | |
| Remission induction | 33 (67.3) |
| Reinduction I (LR) | 2 (4.1) |
| Reinduction II (LR) | 4 (8.2) |
| Continuation (IR/HR) | 5 (10.2) |
| Reinduction (IR/HR) | 3 (6.1) |
| Preprocessing for HSCT | 1 (2.0) |
| HR3’ | 1 (2.0) |
| Chemotherapy in regimen (n=49) | |
| DVLP | 16 (32.7) |
| CAT | 13 (26.5) |
| CAT+VCR+Asp (IR/HR) | 4 (8.2) |
| Dex+Ara-C+VCR+Asp (IR/HR) | 3 (6.1) |
| Dex+DNR+VCR+Asp (LR) | 6 (12.2) |
| Dex+DNR+VCR+Asp+6-MP (IR/HR) | 5 (10.2) |
| DNR+Ara-C+vp-16+Asp (DAEL) | 1 (2.0) |
| Dex+VCR+HD-MTX+CTX+Ara-C+Asp | 1 (2.0) |
| AAP severity (n=49) | |
| Mild/moderate | 26 (53.1) |
| Severe | 23 (46.9) |
| Outcome of primary disease (n=49) | |
| Alive in remission | 34 (69.4) |
| Alive in primary disease relapse | 6 (12.2) |
| Dead | 9 (18.4) |
Table 2.
Clinical manifestations of AAP patients
| Clinical manifestations | AAP patients (%) or duration days |
|---|---|
| Abdominal pain as onset symptoms | 47 (95.9) |
| Localized | 29 (61.7) |
| Diffused | 18 (38.3) |
| Other clinical symptoms | |
| Nausea | 23 (46.9) |
| Vomiting | 26 (53.1) |
| Diarrhea | 5 (10.2) |
| Fever | 26 (53.1) |
| Gastric-intestinal bleeding | 4 (8.2) |
| Diagnosis related | |
| Enzymes ≥3 times UNL | 49 (100) |
| Imaging evidence | 40 (81.6) |
| Clinical symptoms | 49 (100) |
| Systemic complication | |
| Septic shock or hypovolemic shock | 16 (32.7) |
| Hypoproteinemia | 9 (18.4) |
| Electrolyte disorder | 7 (14.3) |
| Coagulation disorder | 4 (8.2) |
| Disseminated intravascular coagulation | 4 (8.2) |
| Diabetic ketoacidosis | 1 (2.0) |
| Multiple organ failure | 3 (6.1) |
| Local complication | |
| Abdominal ascites | 20 (40.8) |
| Peri-pancreatic fluid | 12 (24.5) |
| Pseudocyst | 5 (10.2) |
| Intestinal obstruction | 3 (6.1) |
| Duration | |
| Days from last PEG-Asp to diagnosis (n =45) | 13 (1-50) |
| Days from amylase level onset to peak | 2 (1-43) |
| Days from amylase elevation to normalization | 10 (1-355) |
Table 3.
Laboratory and radiographic ratio of patients with AAP
| Laboratory and radiographic results | Patients with AAP (%) or value of the test results |
|---|---|
| Serum pancreatic enzyme | |
| Peak amylase level, U/L | 1,035 (40-3,149) |
| Normal | 2 (4.1) |
| <3 times UNL | 14 (28.6) |
| ≥3 times UNL | 35 (71.4) |
| Peak lipase level | 1,742 (899-4,545) |
| Normal | 0 (0) |
| <3 times UNL | 1 (2.0) |
| ≥3 times UNL | 48 (98.0) |
| Liver enzyme | |
| Alanine aminotransferase, U/L | 69 (9-587) |
| <69 | 24 (49.0) |
| 70-138 | 11 (22.4) |
| ≥139 | 14 (28.6) |
| Aspartate aminotransferase, U/L | 57 (13-1,185) |
| <46 | 19 (38.8) |
| 47-92 | 11 (22.4) |
| ≥93 | 19 (38.8) |
| Other test results | |
| Total bilirubin, μmol/L | 26.3 (6.9-250.2) |
| Prothrombin time, s | 14.8 (6.8-45.3) |
| Activated partial thromboplastin time, s | 43.7 (21-180) |
| Fibrinogen, g/L | 1.05 (0.20-5.86) |
| Creatine, μmol/L | 30 (13-167) |
| Blood urea nitrogen, mmol/L | 7.4 (1.5-52.6) |
| Radiographic detected cases | |
| Ultrasound (n=45) | 35 (77.8) |
| Contrast CT (n=36) | 24 (66.7) |
Table 4.
Comparation of baseline characteristics of mild/moderate and severe AAP in patients with ALL
| Variables | Mild/moderate AAP (n=24) | Severe AAP (n =20) | P-value |
|---|---|---|---|
| Age, years | 0.008 | ||
| 0-9.9 | 19 (79.2) | 8 (40) | |
| ≥10 | 5 (20.8) | 12 (60) | |
| Baseline WBC counts | 0.490 | ||
| <50×109/L | 20 (83.3) | 14 (70) | |
| ≥50×109/L | 4 (16.7) | 6 (30) | |
| Risk | 0.657 | ||
| LR | 6 (25) | 3 (15) | |
| IR/HR | 18 (75) | 17 (85) | |
| Sex | 0.952 | ||
| Female | 7 (29.2) | 6 (30) | |
| Male | 17 (70.8) | 14 (70) | |
| Immunophenotype | 1.000 | ||
| B-ALL | 19 (79.2) | 15 (75) | |
| T-ALL | 5 (20.8) | 5 (25) |
Table 5.
Clinical outcome and prognosis of patients with AAP
| Variables | All patients (n=49) | Mild/Moderate AAP (n=26) | Severe AAP (n=23) | P-value |
|---|---|---|---|---|
| Patients admitted to the PICU | <0.001 | |||
| Yes | 22 (44.9) | 5 (19.2) | 17 (73.9) | |
| No | 27 (55.1) | 21 (80.8) | 6 (26.1) | |
| Length of PICU stay, d | 7.5 (2-20) | 5 (2-16) | 9 (3-20) | 0.048 |
| AAP outcome | 0.019 | |||
| Alive | 44 (89.8) | 26 (100) | 17 (73.9) | |
| Death | 5 (10.2) | 0 | 6 (26.1) | |
| Impact on chemotherapy | 0.070 | |||
| Discontinue the chemotherapy protocol completely | 9 (18.4) | 2 (7.7) | 7 (30.4) | |
| Continue the chemotherapy without Asp | 28 (57.1) | 15 (57.7) | 13 (56.5) | |
| Continue the chemotherapy with Asp | 12 (24.5) | 9 (34.6) | 3 (13.1) | |
| Primary disease outcome | 0.905 | |||
| Death | 9 (30.6) | 4 (15.4) | 5 (21.7) | |
| Relapse | 6 (69.4) | 3 (11.5) | 3 (13.1) | |
| Alive | 34 (69.4) | 19 (73.1) | 15 (65.2) |
| 1 |
Narta UK, Kanwar SS, Azmi W. Pharmacological and clinical evaluation of L-asparaginase in the treatment of leukemia. Crit Rev Oncol Hematol. 2007; 61(3): 208-21.
doi: 10.1016/j.critrevonc.2006.07.009 |
| 2 |
Ettinger LJ, Ettinger AG, Avramis VI, Gaynon PS. Acute lymphoblastic leukaemia: a guide to asparaginase and pegaspargase therapy. BioDrugs. 1997; 7(1): 30-9.
pmid: 18031078 |
| 3 | Sallan SE, Gelber RD, Kimball V, Donnelly M, Cohen HJ. More is better! Update of Dana-Farber Cancer Institute/Children’s Hospital childhood acute lymphoblastic leukemia trials. Haematol Blood Transfus. 1990; 33((4)): 459-66. |
| 4 |
Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, et al. Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood. 2001; 97(5): 1211-8.
doi: 10.1182/blood.v97.5.1211 pmid: 11222362 |
| 5 |
Keating MJ, Holmes R, Lerner S, Ho DH. L-asparaginase and PEG asparaginase—past, present, and future. Leuk Lymphoma. 1993; 10 Suppl: 153-7.
doi: 10.3109/10428199309149129 |
| 6 |
Bade NA, Lu C, Patzke CL, Baer MR, Duong VH, Law JY, et al. Optimizing pegylated asparaginase use: an institutional guideline for dosing, monitoring, and management. J Oncol Pharm Pract. 2020; 26(1): 74-92.
doi: 10.1177/1078155219838316 |
| 7 |
Helbig G, Armatys A, Boral K, Kopinska AJ, Wozniczka K, Dworaczek M, et al. Safety profile of a single pegylated asparaginase (PEG-ASP) dose in remission induction for acute lymphoblastic leukemia (ALL). Neoplasma. 2018; 65(6): 993-7.
doi: 10.4149/neo_2018_180214N121 pmid: 29940768 |
| 8 |
Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 2007; 12(8): 991-8.
doi: 10.1634/theoncologist.12-8-991 |
| 9 |
Emadi A, Zokaee H, Sausville EA. Asparaginase in the treatment of non-ALL hematologic malignancies. Cancer Chemother Pharmacol. 2014; 73(5): 875-83.
doi: 10.1007/s00280-014-2402-3 |
| 10 |
Rodriguez V, Kairalla J, Salzer WL, Raetz EA, Loh ML, Carroll AJ, et al. A pilot study of intensified PEG-asparaginase in high-risk acute lymphoblastic leukemia: children’s oncology group study AALL08P1. J Pediatr Hematol. 2016; 38(6): 409-17.
doi: 10.1097/MPH.0000000000000589 |
| 11 |
Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, O’Brien JE, et al. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015; 16(16): 1677-90.
doi: 10.1016/S1470-2045(15)00363-0 |
| 12 |
Schmiegelow K, Attarbaschi A, Barzilai S, Escherich G, Frandsen TL, Halsey C, et al. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus. Lancet Oncol. 2016; 17(6): e231-9.
doi: 10.1016/S1470-2045(16)30035-3 pmid: 27299279 |
| 13 |
Samarasinghe S, Dhir S, Slack J, Iyer P, Wade R, Clack R, et al. Incidence and outcome of pancreatitis in children and young adults with acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003. Br J Haematol. 2013; 162(5): 710-3.
doi: 10.1111/bjh.12407 |
| 14 |
Wolthers BO, Frandsen TL, Baruchel A, Attarbaschi A, Barzilai S, Colombini A, et al. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study. Lancet Oncol. 2017; 18(9): 1238-48.
doi: 10.1016/S1470-2045(17)30424-2 |
| 15 |
Raja RA, Schmiegelow K, Albertsen BK, Prunsild K, Zeller B, Vaitkeviciene G, et al. Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol. Br J Haematol. 2014; 165(1): 126-33.
doi: 10.1111/bjh.12733 |
| 16 |
Wolthers BO, Frandsen TL, Abrahamsson J, Albertsen BK, Helt LR, Heyman M, et al. Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol. Leukemia. 2017; 31(2): 325-32.
doi: 10.1038/leu.2016.203 pmid: 27451978 |
| 17 | Liu CC, Yang WJ, Devidas M, Cheng C, Pei DQ, Smith C, et al. Clinical and genetic risk factors for acute pancreatitis in patients with acute lymphoblastic leukemia. J Clin Oncol. 2016; 34(18): 2133-40. |
| 18 |
Alvarez OA, Zimmerman G. Pegaspargase-induced pancreatitis. Med Pediatr Oncol. 2000; 34(3): 200-5.
pmid: 10696127 |
| 19 |
Knoderer HM, Robarge J, Flockhart DA. Predicting asparaginase-associated pancreatitis. Pediatr Blood Cancer. 2007; 49(5): 634-9.
pmid: 16937362 |
| 20 |
Silverman LB, Supko JG, Stevenson KE, Woodward C, Vrooman LM, Neuberg DS, et al. Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia. Blood. 2010; 115(7): 1351-3.
doi: 10.1182/blood-2009-09-245951 pmid: 20007809 |
| 21 |
Asselin B. The three asparaginases. Comparative pharmacology and optimal use in childhood leukemia. Adv Exp Med Biol. 1999; 457:621-9.
pmid: 10500842 |
| 22 |
Minowa K, Suzuki M, Fujimura J, Saito M, Koh K, Kikuchi A, et al. L-asparaginase-induced pancreatic injury is associated with an imbalance in plasma amino acid levels. Drugs R D. 2012; 12(2): 49-55.
doi: 10.2165/11632990-000000000-00000 pmid: 22594522 |
| 23 |
Raja RA, Schmiegelow K, Frandsen TL. Asparaginase-associated pancreatitis in children. Br J Haematol. 2012; 159(1): 18-27.
doi: 10.1111/bjh.12016 |
| 24 |
Oparaji JA, Rose F, Okafor D, Howard A, Turner RL, Orabi AI, et al. Risk factors for asparaginase-associated pancreatitis: a systematic review. J Clin Gastroenterol. 2017; 51(10): 907-13.
doi: 10.1097/MCG.0000000000000827 |
| 25 |
Raja RA, Schmiegelow K, Henriksen BM, Leth Frandsen T. Serial ultrasound monitoring for early recognition of asparaginase associated pancreatitis in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol. 2015; 32(7): 474-81.
doi: 10.3109/08880018.2015.1055868 |
| 26 |
Stock W, Dan DE, DeAngelo DJ, Arellano M, Advani A, Damon L, et al. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: recommendations of an expert panel. Leuk Lymphoma. 2011; 52(12): 2237-53.
doi: 10.3109/10428194.2011.596963 |
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