Acute Appendicitis in Children with Leukemia: Unique Diagnostic Process, Management, and Outcome
Authors: Perrino Melissa , Fernandez-Pineda Israel , Zhou Yinmei , Sandoval John , Jeha Sima , Rubnitz Jeffrey E , Pui Ching-Hon , Inaba Hiroto 
Published: November 2019

Abstract
BACKGROUND
Appendicitis is the most common surgical illness in children and adolescents. However, its incidence and clinical characteristics in pediatric patients with leukemia are not known. Grading pediatric appendicitis score and performing surgery, methods commonly used in non-oncologic populations, may not be the best approaches for patients with leukemia because of the presence of neutropenia and immunosuppression.
PATIENTS AND METHODS
We retrospectively evaluated the incidence and clinical characteristics of appendicitis in children with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who were treated from 1990 to 2014 at St. Jude Children's Research Hospital. Appendicitis cases were carefully evaluated based on radiographic evidence of appendicitis (i.e., enlarged appendix size ≥6mm, inflammation and free fluid, free air consistent with perforation, or abscess or phlegmon in appendix) and surgical consults because of suspected appendicitis.
RESULTS
Of the 1971 patients (1529 with ALL and 442 AML), 19 (1.0%, 10 boys and 9 girls) were identified as having radiographic and/or pathologic appendicitis. The prevalence was similar in ALL (14 of 1529, 0.9%) and AML (5 of 442, 1.1%). The median ages at diagnosis of appendicitis were also similar in ALL and AML: 7.1 years (range, 3.2-14.3 years) and 7.8 years (range, 4.8-13.0 years), respectively. Of interest, appendicitis often developed during remission induction for both ALL (8 during induction, 4 during continuation, 1 during salvage therapy for relapse, and 1 off-therapy) and AML (2 during induction, 2 during consolidation, and 1 after hematopoietic stem cell transplantation [HSCT] for relapse).
Abdominal pain was present in 17 (89.5%) patients and fever in 15 (79.0%). Right lower quadrant tenderness was seen in 17 patients (89.5%), with guarding in 11 (57.9%). Median white blood cell (WBC) counts were 1.4 × 109/L (range, 0.1-8.7 × 109/L), and median absolute neutrophil (ANC) counts were 0.8 × 109/L (0-7.7 × 109/L); 9 patients (47.3%) had an ANC < 0.5 × 109/L. The median pediatric appendicitis score at presentation was 4 (range, 1-7), below the criteria to consider appendicitis (≥6) in the general population, mainly due to low WBC and ANC as well as low frequency of migration of pain. Computed tomography and/or ultrasound imaging were used in 18 cases (94.7%). Inflammation of the appendix was seen in 15 cases, which had a median appendix size of 8.5 mm (range, 4-17 mm). In addition, 12 cases had ascites, 7 had evidence of perforation (3 with free air), 6 had phlegmon formation, and 5 had an appendicolith.
Eleven patients underwent surgery (5 open laparotomy and 6 laparoscopic surgery), and 8 were managed without surgery. Compared with surgical patients, non-surgical patients had lower pediatric appendicitis scores (median, 5 vs. 3, P = 0.023), ANC (2.1 vs. 0.1 × 109/L, P = 0.018), and frequency of rebound tenderness (5 vs. 0 patients, P = 0.045). Pathologic findings in surgical patients included necrosis (n = 4), perforation (n = 3), focal appendiceal hemorrhage (n = 3), polyclonal lymphoid hyperplasia (n = 1), and gangrenous lesion (n = 1). No leukemia involvement was observed. Broad coverage of antibiotics was used in most cases: vancomycin in 16 cases (84.2%), meropenem in 17 (89.4%), and tobramycin in 14 (73.7%). No patient died of appendicitis. Although the management of chemotherapy differed significantly among individual patients, interruption in chemotherapy was minimal. In the 8 patients with ALL who developed appendicitis during induction, chemotherapy was held for a median of 6.5 days (range, 0-16 days). There were 2 relapses after episodes of appendicitis: 1 isolated testicular ALL relapse (appendicitis during continuation) and 1 marrow AML second relapse (appendicitis after HSCT for the first relapse).
CONCLUSION
Acute appendicitis occurred in 1% of children with leukemia, and often developed during remission induction. Although pediatric appendicitis scoring was not useful for diagnosis, patients with lower scores could be successfully managed without surgery and without mortality from this complication.

Disclosures
No relevant conflicts of interest to declare.