Reduced Treatment for Good Risk Pediatric Acute Lymphoblastic Leukemia Patients Leads to a Decrease in Infectious Morbidity.
Authors: van Tilburg Cornelis M , Sanders Elisabeth A.M. , Wolfs Tom F.W. , Pieters Rob , Bierings Marc B 
Published: October 2019

Abstract
Abstract 983
Poster Board I-5

Introduction:
Tailored, intensified therapy has led to improved survival of pediatric acute lymphoblastic leukemia (ALL). However, intensified therapy leads to more infectious morbidity. The aim of this study is to investigate to what extent less intensive therapy in good risk patients decreases infectious morbidity.

Patients and Methods:
203 children newly diagnosed with ALL between 1 and 19 years old were included in all 8 University Medical Centers in the Netherlands between 2004 and 2007 and followed prospectively until end of treatment. All patients kept a diary by which admittances for infection were reported. All these admittances were systematically reviewed by the investigators in the clinical files. Infections occurring during hospital stay for other indications (e.g. chemotherapy) or present at the time of diagnosis of ALL were also recorded but not included in this analysis. Patients were stratified into 3 arms identical to BFM-2000 criteria with a reduced treatment for good risk patients: standard risk (SR), an intensified reinduction treatment for medium risk patients (MR) and series of intensive courses of chemotherapy in most cases combined with allogeneic stem cell transplantation for high risk patients (HR). Statistics: All variables were corrected for patient time in study (standard 104 weeks). After logarithmic transformation data was evaluated using ANOVA.

Results:
55 children were stratified to SR group, 123 to MR group and 21 to HR group. SR patients were followed for a mean of 102 weeks, MR 100 weeks and HR 47 weeks. A total of 507 admittances for infection were recorded. SR patients were admitted 1.1 times on average, versus 3.4 for MR and 6.9 for HR patients (p<0.001) (see figure). In addition, SR patients were less days admitted for infection (median SR: 5.0 versus MR: 14.7 and HR: 51.2 days, p<0.001) and had less positive blood cultures (mean SR: 0.29 versus MR: 0.70 and HR: 2.10, p<0.001 for SR versus HR, SR versus MR not significant). SR patients had most of their infections during induction, not during the reduced SR therapy while MR and HR patients had infections during the whole treatment period. Of all infections recorded, 20% were upper respiratory tract infections, 13% were isolated bacteremia only, 7% were pneumonia and 37% were fever without a cause. 10 admittances for infection to the intensive care unit were recorded in the MR group, one patient died. No intensive care unit admittances for infection during study for the SR group were recorded. Chemotherapy interruption because of infection was done on average 0.4 times in SR patients versus 1.9 times in MR patients and 1.0 times in HR patients (p<0.05).

Conclusions:
Less intensive treatment for SR pediatric ALL patients significantly decreases infectious morbidity for this group. The frequency, duration and severity of admittances for infection are all significantly reduced underlining the benefits of reduced therapy for good risk ALL patients. In addition, reduced therapy for SR patients leads to less chemotherapy interruption and thus compliance with the chemotherapy schedule is more easily achieved.

Disclosures:
No relevant conflicts of interest to declare.