Discussion
The utilization of pediatric-inspired regimens in AYAs diagnosed with
ALL has been realized through concerted efforts among multiple
international groups; however, information on BSIs for AYAs remains
unclear. This study represents one of the largest to date and one of the
first among Chinese patients to examine BSI-related event profiles among
AYAs diagnosed with ALL. Here, we found that the epidemiology and
resistance patterns of bacterial pathogens in AYAs diagnosed with ALL
were more similar to those in adult ALL patients, while the prognostic
factors were different between younger children and older adult
patients.
Modern cancer therapies suggest that more AYAs diagnosed with ALL
treated with a pediatric-inspired regimen had better outcomes, yet we
found that AYAs patients actually suffered from profound neutropenia and
poorer nutritional status compared to children with ALL in the process
of BSIs. Our results were consistent with a study conducted by St. Jude
Children’s Research Hospital, which showed that ALL patients aged over
10 years had more severe neutropenia in all phases of chemotherapy than
those aged between 1 and 9.9 years.[12] This may be related to the
reduced tolerance to chemotherapy in AYAs with ALL compared to children
with the same regimen due to differences in pharmacokinetics, drug
sensitivity, and organ function.[13 14] In addition, our study
showed that AYAs patients had a poorer prognosis than children with ALL
(16.1% vs. 11%). The poorer prognosis may be associated with
independent psychosocial and economic factors of AYAs patients, which
have been proposed as potential causes of reduced compliance.[15-17]
Although several studies have demonstrated the feasibility of
pediatric-inspired regimens in AYAs for ALL patients, their chemotherapy
tolerance and BSI-related events may limit the applicability of
treatment.
Regarding the resistance patterns of bacterial pathogens, the detection
rate of ESBL was significantly higher in the AYAs group than in the
children (32.8% vs. 16.4%, P=0.09) . This rate is similar as our
previous report of haematological-associated bloodstream infections in
adults and other reports.[18-20] This result was probably related to
the fact that AYAs patients received a higher proportion of antibiotic
exposure (70% vs. children:35.6%, P< 0.001), especially
cephalosporin antibiotics. It is worth noting that ESBL-producing BSIs
did not increase 30-day mortality in any of the three groups, which may
be associated with appropriate initial antimicrobial therapy in all
three groups (AYAs:85.6%, children:89%, adults:90%).[21 22]
Regarding the resistance patterns of GPB, our study showed that the
detection rates of MRS in the AYAs and adult groups were significantly
lower than those in children with ALL. Notably, despite the higher
detection rate of MRS in children, MRS with methicillin-resistant
coagulase-negative staphylococci (MRSCN) accounted for 92.3% of
children, which is relatively less virulent according to previous
studies.[23 24] In addition, penicillin prevention in children with
ALL is used to prevent infection; hence, MRS rarely incurs rapid disease
progression or even death among children.
According to our data, there was no difference in the survival
disadvantages of AYAs compared with the other two groups. To our
knowledge, only limited data regarding the analysis of prognostic
factors affecting BSIs in patients were available. By in-depth analysis
of the data to explore the prognostic factors influencing 30-day
mortality, we found that acute respiratory failure during BSIs was an
important influencing factor in all three groups. Our study also
suggests that AYAs ALL patients with BSIs are likely to have unique
characteristics, as evidenced by their other prognostic factors. Renal
inadequacy is an independent prognostic factor for BSIs in AYAs,
indicating the importance of organ function management during BSIs in
AYAs. Moreover, we found that a longer hospital stay was a protective
factor for BSIs among AYAs ALL patients. The effect of the length of
hospitalization on mortality in patients with HM has been controversial
in previous studies. Basu et al. assessed AYAs as a high-risk group in
cancer patients with febrile neutropenia, whom had 1.5 times a hospital
stay, 3 times mortality than that of children aged 1 to 12
years.[25] In contrast to the previous result, we speculate that
AYAs patients with BSIs with shorter hospital stays have higher
mortality rates due to rapid organ failure and poorer nutritional status
(see Supplemental Material).
Our study has some limitations. Some data on possible BSI in patients
with HM may have been missed. Missing values for some variables in the
retrospective dataset could have resulted in underestimation or
overestimation of the results of interest. Due to the inconsistent
infection monitoring and evaluation indicators in the three hospitals,
and the incomplete collection of inflammatory indicators, such as
procalcitonin (PCT), erythrocyte sedimentation rate (ESR), C-reactive
protein (CRP), and IL-6, which measure the severity of infection.
Inflammation indicators were not included, and the impact of the
patient’s infection severity on prognosis was not explained from the
objective data.
Although the pediatric-inspired regimen is feasible, most AYAs patients
suffer from profound neutropenia and poorer nutritional status compared
to children with ALL, which may limit the applicability of therapeutic
regimens in AYAs. In addition, the pathogen distribution of AYAs in our
study was similar to that in adult ALL patients, suggesting that the
whole process management of BSIs of AYAs may be more inclined toward
adults. Finally, the findings of our study strengthen the management of
AYAs patients during hospitalization and the monitoring of organ
function levels, which may help improve outcomes.