Septicemia after Chemotherapy for Acute Lymphoblastic Leukemia: A Multicenter Study Chinese Children Cancer Group (CCCG)-ALL-2015

Introduction: Septicemia is one of the common complications after chemotherapy for acute lymphoblastic leukemia (ALL) and is also an important cause of treatment related mortality and treatment failure. A multicenter study CCCG-ALL-2015 was conducted in China and factors associated with septicemia and mortality were studied.

Methods: Patients participated in CCCG-ALL-2015 study from January 2015 to December 2017 were included in this study. Patients with documented septicemia were identified from the Database of Central Data Center. Additional data were then collected from participation centers, including associated co-morbidity, blood counts before septicemia and infection preventive measures.

Results: A total of 4080 patients were recruited from 18 centers. There were 527 patients with septicemia identified (12.9%). The Intermediate risk (IR)/ High risk (HR) group(n=1930) had significantly higher incidence of septicemia as compared with Low risk (LR) group (n=2150), 17.15% vs 9.12% (p<0.001). Among the IR/HR group, children with Philadelphia (Ph) positive ALL (n=166) had similar incidence of septicemia as compared with Ph negative group (n=1764), 20.5% vs 16.8% (p =0.14). Induction phase was the period with most septicemia episodes occurred, 66.3% in LR and 56.1% in IR/HR groups. There was another peak of septicemia in IR/HR group during the re-induction phase (18%) and early maintenance phase at week 35-54 (9.3%). Gram positive bacteria accounted for 54.2%, Gram negative bacteria 44.5% and fungus 1.4% of positive cultures. The top 10 isolates were Coagulase negative staphylococcus (20.1%), staphylococcal epidermidis (14.6%), E. Coli (11.5%, 29/68 were ESBL), klebsiella pneumonia (8%, 7/47 were ESBL), pseudomonas aeruginosa (7%, 2/41 were ESBL), staphylococcus aureus (5.6%, 8/33 were MRSA), streptococcal mitis (3.2%), streptococcal pneumonia (3%), salmonella (2%) and Enterobacter cloacae (1.7%). Multi-drug resistant organisms were detected in 20.5% of all organisms. The mortality rate after septicemia was 3.2%. Multiple logistic regression identified female gender, comorbid complications and fungal infection as risk factors associated with mortality. Gram negative septicemia was also associated with higher mortality, 4.9% vs 1.9% (P<0.05%). There was marked variation in the incidence of septicemia among the 18 centers, from 4.8% to 29.1%. Centers allowed additional beds opened in the ward due to full occupancy had higher incidence of septicemia, 16.3% (342/2101) vs 11% (218/1979), p <0.001. Centers with the practice of using modular High Efficiency Particulate Air (HEPA) filter units in the wards for patients with severe neutropenia had lower incidence of septicemia, 8.3% (118/1430) vs 16.7% (442/2650), p<0.001. Prophylactic use of G-CSF at time of neutropenia (neutrophils < 0.5x10⁹/L) was also associated with lower incidence of septicemia, 10.1% (165/1626) vs 16.1% (442/2650). Similarly prophylactic intravenous immunoglobulin and antibiotics was also associated with lower incidence of septicemia, 8.9% (78/877) vs 15% (481/3203) and 7.8% (70/970) vs 18.7% (490/3110) respectively.

Conclusion: Overall the incidence and pattern of septicemia in this multicenter study in China was similar to reports of western countries. The septicemia related mortality rate was low. However there was marked variation in the incidence of septicemia among the centers, further studies are required to validate factors such as infection preventive measures which might influence the septicemia incidence.