Effectiveness of Antibacterial Prophylaxis during Induction Chemotherapy in Children with Acute Lymphoblastic Leukemia
Bibliographic record
Abstract
Abstract Background. Pediatric patients with newly diagnosed acute lymphoblastic leukemia (ALL) are at high risk for developing bacterial infections, particularly during the induction treatment phase. Infections are the primary cause of treatment-related mortality during the induction phase, and also lead to prolonged hospitalization, as well as delays and dose modifications in planned chemotherapy. On DFCI ALL Consortium Protocol 05-001 (2005-2011), 26.6% of 794 enrolled patients (pts) experienced at least one infectious complication during induction. In the subsequent study, DFCI Protocol11-001, we studied whether the use of prophylactic fluoroquinolones during induction would decrease the incidence of bacterial infections. Patients and methods.Between 2012-2015, 229 pts with ALL (aged 1-21 years) were enrolled on Protocol 11-001 at 9 participating sites. Induction therapy, regardless of risk group, included vincristine, methylprednisolone, doxorubicin, low-dose methotrexate and pegylated L-asparaginase. Afebrile pts were started on fluoroquinolone prophylaxis at the time of initiation of therapy and continued until count recovery at the end of induction. Pts were switched to broad-spectrum antibiotics (eg, cefepime) for fever or documented infection. Pts with fever at presentation were started on broad spectrum antibiotics rather than fluoroquinolone, and either remained on broad-spectrum antibiotics or were switched to fluoroquinolone prophylaxis until count recovery per treating clinician. Antifungal prophylaxis was not required. All episodes of microbiologically documented bacterial infection, microbiologically and/or radiographically documented fungal infection, and Clostridium difficile (C. diff) enterocolitis were prospectively collected. Using a 1-sample binomial test, rates of infections on Protocol 11-001 were compared to those from the predecessor study, DFCI Protocol 05-001, which included nearly identical induction chemotherapy but did not include guidelines regarding antibiotic prophylaxis or duration during induction. Results. Of the 229 pts, 89% had B-ALL and 11% T-ALL. Median age was 5.1 yrs (range 1.0-20.9). Eighty-six afebrile pts (37.5%) were administered upfront antibiotic prophylaxis and 141 (61.6%) had fever at diagnosis and received broad-spectrum antibiotics; two afebrile patients did not receive antibiotic prophylaxis for unknown reasons. Of the 86 pts who began prophylaxis, 37 (43%) subsequently developed fever. Toxicity data was available for 222 pts. Thirty-eight episodes of infection occurred in 29 patients. Age, presenting white blood cell count and immunophenotype were not associated with the development of infection. The proportion of pts experiencing an infection on Protocol 11-001 (13.1%) was significantly lower than on Protocol 05-001 (26.6%, p<0.0001) [Figure 1]. The observed reduction was due to a decrease in the incidence of bacterial infection (9.9% vs 24.7%, p<0.0001). Of note, there were significantly fewer episodes of bacteremias due to Gram negative rods, S. aureus and S. viridans on Protocol 11-001 compared to 05-001. There was no significant difference in incidence of fungal infection between the two protocols (4.5% vs 3.9%, p=0.32). Twenty (9%) pts on 11-001 developed C. diff colitis during induction (16 Grade 2, 3 Grade 3, 1 Grade 4). The induction death rate on Protocol l 11-001 was 0.9% compared with 2% on Protocol 05-001 (p=0.24). Conclusion.The results of our prospective, multi-institutional non-randomized study indicate that treating newly diagnosed pediatric ALL pts with antibiotics throughout the induction phase (including the use of antibiotic prophylaxis for afebrile pts) is effective at reducing the incidence of bacterial infections, and does not result in an increase in fungal infections or a high incidence of C. diff colitis. Additional larger, randomized studies are necessary to confirm the safety and efficacy of this approach during the induction phase. Figure 1. Rate of induction (A) overall (bacterial/fungal), (B) bacterial, (C) fungal infections on Protocols 05-001 and 11-001 Figure 1. Rate of induction (A) overall (bacterial/fungal), (B) bacterial, (C) fungal infections on Protocols 05-001 and 11-001 Disclosures No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".