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.