Clinical and Genetic Risk Factors for Acute Pancreatitis in Patients With Acute Lymphoblastic Leukemia Hematologic Malignancy

Purpose Acute pancreatitis is one of the common causes of asparaginase intolerance. The mechanism is unknown, and genetic predisposition to asparaginase-induced pancreatitis has not been previously identified. Methods To determine clinical risk factors for asparaginase-induced pancreatitis, we studied a cohort of 5,185 children and young adults with acute lymphoblastic leukemia, including 117 (2.3%) who were diagnosed with at least one episode of acute pancreatitis during therapy. A genome-wide association study was performed in the cohort and in an independent case-control group of 213 patients to identify genetic risk factors. Results Risk factors associated with pancreatitis included genetically defined Native American ancestry (P
Source: Journal of Clinical Oncology - Category: Cancer & Oncology Authors: Tags: Acute Lymphoblastic Leukemia Hematologic Malignancy Source Type: research

Related Links:

Asparaginase (ASP) and steroids are a main part of treatment for ALL, in both front-line and relapse setting. It is known, that ASP can cause several toxicities such as hypersensitivity, pancreatitis, as well as severe lipid and coagulation disturbances. Administered steroids can result in diabetes, obesity, hyponatremia and also mild hyperlipemia, which can intensify side effects of asparaginase. When triglyceride elevation is greater than 1000  mg/dl, the risk of pancreatitis is significantly increased.
Source: Transfusion and Apheresis Science - Category: Hematology Authors: Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Xiaoli Fan1†, Dandan Yin2†, Ruoting Men1, Heng Xu2* and Li Yang1* 1Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China 2Department of Laboratory Medicine, National Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy and Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, China The aim of this study was to investigate the influence of NUDT15 R139C and thiopurine S-methyltransferase (TPMT) on azathioprine (AZA) induced leukopenia in patients with autoimmune hepatitis (AIH) a...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Acute pancreatitis in children acute lymphoblastic leukemia is commonly caused by drugs, for example, L-Asparaginase, pegapargase, steroids. The incidence of this complication is estimated at 6.7% to 18%. Although the majority of drug-induced acute pancreatitis cases are mild, severe cases can rarely occur. This work presents a case of successful management of a child with drug-induced necrotizing pancreatitis during acute lymphoblastic leukemia therapy. This case illustrates that comprehensive care and immediate intensive treatment can rescue patient despite poor prognosis. Administration of octreotide may serve a role in...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Clinical and Laboratory Observations Source Type: research
Publication date: December 2018Source: The Lancet Haematology, Volume 5, Issue 12Author(s): Elias Jabbour, Nicholas J Short, Farhad Ravandi, Xuelin Huang, Naval Daver, Courtney D DiNardo, Marina Konopleva, Naveen Pemmaraju, William Wierda, Guillermo Garcia-Manero, Koji Sasaki, Jorge Cortes, Rebecca Garris, Joseph D Khoury, Jeffrey Jorgensen, Nitin Jain, Joie Alvarez, Susan O'Brien, Hagop KantarjianSummaryBackgroundThe combination of chemotherapy and ponatinib in Philadelphia chromosome-positive acute lymphoblastic leukaemia has the potential to be a new standard of care for the disease; however, long-term efficacy and safe...
Source: The Lancet Haematology - Category: Hematology Source Type: research
ang W, Zapotocka E, Gupta R, Schmiegelow K Abstract Asparaginase-associated pancreatitis is a life-threatening toxicity to childhood acute lymphoblastic leukemia treatment. To elucidate genetic predisposition and asparaginase-associated pancreatitis pathogenesis, ten acute lymphoblastic leukemia trial groups contributed remission samples from patients aged 1.0-17.9 years and treated from 2000-2016. Cases were defined (n=244) by at least two of the following criteria: i) abdominal pain, ii) pancreatic enzymes>3 x upper normal limit, iii) imaging compatible with asparaginase-associated pancreatitis. Controls (n=1...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Introduction: Treatment for acute lymphoblastic leukemia (ALL) with asparaginase (ASP) and glucocorticoids, such as dexamethasone (DEX), can cause changes in serum triglycerides (TGs). Glucocorticoids increase the activity of lipoprotein lipase (LPL), the enzyme responsible for removing TGs from the plasma, and increase production of TG-rich particles, resulting in the mobilization and redistribution of body fat. In contrast, ASP decreases the activity of LPL. Therefore, when glucocorticoids and ASP are given together, it is likely that TG-rich particles are rapidly formed, but insufficiently cleared, resulting in elevated...
Source: Blood - Category: Hematology Authors: Tags: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Poster II Source Type: research
Conclusions: Selinexor, at a doses of 30 or 40 mg/m2 given twice weekly, was well tolerated in pediatric and young adult pts with R/R acute leukemia, demonstrating single agent clinical activity and less GI toxicity than had been seen in adults. The high frequency of TLS in ALL pts is particularly notable as treatment of ALL with selinexor has not been previously reported. Analysis of pharmacokinetic and correlative biology studies are underway. Based on the results of this Phase I study, the recommended Phase II dose of single-agent selinexor in children with R/R acute leukemia is 40 mg/m2 administered twice weekly. These...
Source: Blood - Category: Hematology Authors: Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I Source Type: research
We report updated outcomes for ALL patients treated with Ven, Nav, and chemotherapy.Methods: R/R ALL patients aged ≥4 years were enrolled in this phase 1, multicenter, open-label, dose escalation study (NCT03181126). Patients received the weight-adjusted equivalent of 200 mg Ven on day 1, and a 400 mg equivalent daily thereafter. Daily oral Nav was administered on day 3 onward with up to three dose levels for patients ≥45 kg (25, 50, 100 mg) and up to two dose levels for patients
Source: Blood - Category: Hematology Authors: Tags: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Poster III Source Type: research
DiscussionWe detected silent inactivation in a single patient who had an asparaginase level of 0.01 seven days after the first dose of PEG and showed no signs of overt allergic reaction. This patient was switched to Erwinaze and an asparaginase level drawn 48 hours post Erwinaze was therapeutic at 0.719. Another patient developed a hypersensitivity reaction 12-hours after PEG and had a serum asparaginase level of 1.29 7-days post PEG. This suggests that not all anti-asparaginase antibodies are neutralizing since this patient continued to demonstrate therapeutic drug levels. The incidence of allergic reactions to PEG at our...
Source: Blood - Category: Hematology Authors: Tags: 612. Acute Lymphoblastic Leukemia: Clinical Studies: Poster III Source Type: research
More News: Acute Leukemia | Acute Lymphoblastic Leukemia | Cancer & Oncology | Children | Genetics | Hematology | Leukemia | Pancreatitis | Study