1. Insert Program or Hospital Logo Introduction Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It comprises 25% of childhood malignancy occurring before 15 years of age and 19% occurring before 20 years of age. With 5-year and 10-year survival rates for childhood ALL reaching greater than 90% and 84% respectively, increasingly more attention is turning towards treatment-related morbidity and mortality and chemotherapy induced side-effects. Pancreatitis has a reported incidence of 2.4 – 13.2 patients per 100,000 per year in the pediatric population. It can be complicated by pseudocyst, shock, organ failure, and death. Some of its causes include medications, duct obstruction, genetic, infection, and trauma. Drug induced pancreatitis (DIP) affects 3-30% of children diagnosed with pancreatitis; however, the percent of children with ALL who develop pancreatitis is currently unknown. Asparaginase is the most common drug associated with DIP in the Children’s Oncology Group (COG) protocols used to treat the patients in our review. These protocols currently recommend withdrawal of further asparaginase therapy with severe pancreatitis. This dose modification practice may significantly limit the total therapy provided to ALL patients seeking remission. There is currently no other drug-induced recognized cause for pancreatitis developed during ALL treatment. Nor is there another non-drug related cause to substantiate not withdrawing asparaginase from treatment if patients develop pancreatitis during the course of their scheduled chemotherapy. Pancreatitis due to Mercaptopurine and Asparaginase in Acute Lymphoblastic Leukemia Miriam B.G. Morrell, DO, PGY2 1,3, Erica Garcia-Frausto, RN, MSN, CPNP 1,2,3, Chatchawin Assanasen, MD 1,2,3 1 Department of Pediatrics University of Texas Health Science Center at San Antonio, 2 GreeheyChildren’s Cancer Research Institute, 3 Children’s Hospital of San Antonio Results Eight (11%) patients developed pancreatitis. Patients’ ages ranged 3 years old to 18 years old. Of the patients, half were girls and half boys. Five of these patients experienced recurrent episodes of pancreatitis despite withdrawal of asparaginase from their therapeutic regimen. These patients subsequently did not receive up to 74% of their treatment of asparaginase during either the consolidation, interim maintenance, and delayed intensification phases. Two patients developed symptoms 2-3 weeks following 6MP administration in consolidation and then similarly upon resumption of 6MP dosing during maintenance phases of their therapy. Recurrence of their symptoms coincided directly with resumption of standard 6MP doses of 75mg/m 2 /day. In addition to these two patients, three more developed pancreatitis either during consolidation or directly after, subsequent to receiving both 6MP and asparaginase. There were five instances of patients who developed pancreatitis during induction or delayed intensification after only receiving asparaginase. Five patients developed pancreatitis during maintenance or interim maintenance after only receiving 6MP. 6MP dosing was decreased in five to six of the eight patients based on when they developed pancreatitis in relation to 6MP and asparaginase dosing. These patients consequently did not receive up to 61% of their scheduled 6MP in either consolidation or maintenance. The medical record of one of the eight patients did not provide scheduled dosing of either asparaginase or 6MP, only the doses the patient actually received. One patient relapsed and developed pancreatitis during both his initial chemotherapy and relapse chemotherapy. One patient did not develop pancreatitis until relapse. Three patients experienced reduced dosing of 6MP during maintenance due to causes other than pancreatitis. They either developed herpes zoster, abdominal pain not diagnosed as pancreatitis, or documented unintentionally missed doses. Hypothesis 6-Mercaptopurine can cause drug-induced pancreatitis in children undergoing chemotherapy for Acute Lymphoblastic Leukemia. Methods A retrospective chart review was performed on seventy-one active pediatric patients treated with COG ALL protocols from 2008 – 2013. Eight of these patients were identified as pancreatitics based on either imaging or protocol based criteria: abdominal pain >72 hours, ≥ Grade 3 amylase elevation. Data collection focused on the dosing and timing of PEG- asparaginase and 6-mercaptopurine (6MP); however, some patients may have received other drugs associated with pancreatitis. These drugs were excluded because they were not scheduled in the COG protocols, given based on individual circumstances and not required of every patient reviewed, or significant variability exists in individual patient dosing and compliance. Of definitive cause drugs associated with pancreatitis, cytarabine and steroids are scheduled in multiple ALL treatment protocols. We were unable to find any pediatric cases linking either cytarabine or steroids to pancreatitis in the treatment of ALL unassociated with asparaginase. Conclusions We described eight cases of pancreatitis in pediatric patients undergoing therapy for ALL who required withdrawal from asparaginase during the earlier phases of ALL therapy or reduction in 6MP when pancreatitis was developed in the maintenance portion of therapy. These cases suggest that other etiologies for pancreatitis should be considered prior to complete withdrawal of asparaginase based therapies. Such considerations should include mercaptopurine drug-induced pancreatitis or hereditary and genetic causes for pancreatitis. Additionally, with the impact of 6MP on event free survival due to its extensive use in maintenance therapy and its extensive use in chemotherapeutic protocols world-wide, it is necessary to continue to search for predictive measures for the development of pancreatitis and find an alternative solution to abrupt cessation of both 6MP and asparaginase. References 1. Hunger, Stephen P., et al. "Improved Survival for Children and Adolescents with Acute Lymphoblastic Leukemia Between 1990 and 2005: A Report from the Children's Oncology Group." Journal of Clinical Oncology 30.14 (2012): 1663-1669. 2. Childhood ALL Collaborative Group. "Duration and Intensity of Maintenance Chemotherapy in Acute Lymphoblastic Leukaemia: Overview of 42 Trials Involving 12 000 Randomized Children. Childhood ALL Collaborative Group." Lancet 347.9018 (1996): 1783-1788. 3. Lowe ME, et al. “Pancreatitis in children and adolescents” Curr Gastroenterol Rep 2008 Apr;10(2): 128-135. 4. Haber, et al. “Nature and course of pancreatitis caused by 6-mercaptopurine in the treatment of inflammatory bowel disease.” Gastroenterology 91.4 (1986):982-986. 5. Whitcomb, David C. "Genetic Aspects of Pancreatitis." Annual Review of Medicine 61.1 (2010): 413-24. 6. Sultan, Mutaz, et al. “Genetic Prevalence and Characteristics in Children with Recurrent Pancreatitis.” Gastroenterology. 2012 May;54(5):645-50. 7. Raja, et al. “Asparaginase-associated pancreatitis in children” British Journal of Haematology 2012;159:18-27. 8. Relling MV, et al. “Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing.” Clinical Pharmacology and Therapeutics 2011;89(3)387-391. Texas Pediatric Society Electronic Poster Contest PatientAge/Sex PEG (IU) scheduled PEG (IU) received PEG reduced 6MP (mg) scheduled 6MP (mg) received 6MP reduced 1. LL8/M17,5005,00071%26,88019,28028% 2. WS5/F5,0002,62547.5%66,10825,52561% 3. XO3/F15,0005,00067%47,77538,08820% 4r. KA7/Funknown9,300unknown 18,700unknown 5. AM13/M22,9005,92574%69,06865,9404.5% 6i. AT14/M26,25026,3000%115,953114,8281% 6r. AT18/M15,00011,25025%2,520unknown 7. JP17/M23,75011,52552%17,82216,2269% 8. DC12/F16,375 0%53,63443,85418.3% Figure 1. Chemotherapy timelines of Asparaginase and 6MP for patients who developed pancreatitis from 2008 to 2013 at UTHSC-SA Table 1. Patients who developed pancreatitis secondary to Asparaginase or 6-Mercaptopurine and their therapy reduction from 2008-2013 at UTHSC-SA PEG. PEG – Asparaginase, 6MP – 6 Mercaptopurine, i. Findings with initial diagnosis, r. Findings after relapse