Abstract

Abstract 4283

Background

The role of Gemtuzumab ozogamicin (GO) for acute myeloid leukemia (AML) remains controversial. GO was removed from the U.S. market in 2010 due to concerns of increased induction mortality in adults. Other studies have shown a survival benefit without increased treatment related mortality. Moreover, no data are available on the resources required to deliver GO based chemotherapy. Since pediatric data are limited, we evaluated in-hospital mortality and resource utilization in pediatric AML patients treated with GO and standard chemotherapy.

Methods

We used the Pediatric Information Health System (PHIS) to establish a cohort of children < 19 years old treated for de novo AML with GO and standard cytarabine, daunorubicin, and etoposide (ADE) induction. Cohort assembly was validated by local chart review and used ICD-9 diagnosis codes and manual review of chemotherapy. Case fatality was determined after induction (defined from the start of therapy to the initiation course 3), at 6 months and at 12 months. Resource utilization was determined for each patient based on daily billing data. Each resource variable was dichotomized (exposure or no exposure) for each inpatient day and then summarized during each study period to determine resource utilization days per 1,000 hospital days.

Results

In total, 253 children who had billing data for GO during the first course of ADE induction were identified. Median age was 9.6 years; a slight male predominance was observed (54%) and most patients were white (69%). In-hospital case-fatality rates were 2.4% during induction, 6.7% at 6 months, and 13.0% at 12 months from start of therapy. PHIS billing data demonstrated that patients received opioids almost on one in four hospital days, that during induction period 12% of patients received vasopressors on at least two consecutive days, and 12% needed assisted ventilation. Mean inpatient stay and resource utilization rates are presented in Table 1.

Discussion

In-hospital mortality rates at the three time points were low and concordant with published data on pediatric AML trials using an ADE induction (Gibson, BJH 2011) and ADE Induction + GO (Cooper, Cancer 2012) and lower than trials using intensively timed DCTER regimens (Woods, Blood 2001; Lange, Blood 2008). Resource utilization data demonstrated an extensive use of resources needed to manage infections (blood cultures, imaging, antimicrobials). While infections are the leading cause of non-relapse morbidity and mortality in pediatric AML, such extensive use of resources has not been previously quantified. In addition, PHIS billing data describe toxicities such as pain (opioid use), hypotension (vasopressor support), and respiratory failure (assisted ventilation) at rates higher than those previously reported in clinical trials. In conclusion, the in-hospital mortality of children treated with GO at PHIS centers appears comparable to previously published studies of ADE and ADE + GO. The resource utilization data provide a more comprehensive description of resources needed to treat pediatric AML than previously reported. In addition, the resource utilization data suggest that toxicities reported on clinical trials may underestimate the resources needed to administer AML induction therapy safely.

Table 1.

Resource utilization days per 1000 hospital days

ResourceInduction6 months12 months
Inpatient days 56.6 117.3 139.5 
Complete blood counts 898.0 873.6 874.0 
Blood cultures 205.1 222.4 228.6 
Antibiotics    
Total 1079.4 1039.7 1073.0 
Gram-positive coverage 289.4 285.9 298.8 
Beta lactams (Anti-Pseudomonal) 488.1 436.8 434.5 
Carbapenems (Anti-Pseudomonal) 110.2 117.6 120.5 
Quinolones 14.7 23.5 34.7 
Aminoglycosides 169.2 166.2 169.3 
Anti-fungals    
Total 770.3 774.3 790.8 
Amphotericins 104.4 96.6 100.0 
Echinocandins 89.5 96.1 110.3 
Azoles 576.4 581.6 580.6 
Anti-virals 128.7 168.4 203.9 
Blood products    
Packed red blood cells 114.3 116.5 118.1 
Platelets 202.5 206.6 215.5 
Fresh frozen plasma 11.0 8.7 8.2 
Analgesics    
Non-opioid 261.2 270.5 279.1 
Opioid (all routes) 243.2 221.9 240.3 
PCA 18.0 19.3 22.0 
Parenteral nutrition 136.5 130.2 141.4 
Anti-hypertensives 57.4 70.3 92.5 
Diuretics 59.5 63.2 76.8 
Vasopressors    
Dopamine 7.2 7.6 9.3 
Other 12.4 13.5 16.5 
Supplemental oxygen 20.3 20.3 23.5 
Assisted ventilation 17.6 16.8 17.8 
ECMO 0.1 0.07 0.06 
Dialysis 2.2 3.2 5.5 
Imaging    
Chest X-ray 75.6 74.5 80.5 
Head CT 8.6 8.3 8.9 
Chest CT 17.4 18.0 18.5 
ResourceInduction6 months12 months
Inpatient days 56.6 117.3 139.5 
Complete blood counts 898.0 873.6 874.0 
Blood cultures 205.1 222.4 228.6 
Antibiotics    
Total 1079.4 1039.7 1073.0 
Gram-positive coverage 289.4 285.9 298.8 
Beta lactams (Anti-Pseudomonal) 488.1 436.8 434.5 
Carbapenems (Anti-Pseudomonal) 110.2 117.6 120.5 
Quinolones 14.7 23.5 34.7 
Aminoglycosides 169.2 166.2 169.3 
Anti-fungals    
Total 770.3 774.3 790.8 
Amphotericins 104.4 96.6 100.0 
Echinocandins 89.5 96.1 110.3 
Azoles 576.4 581.6 580.6 
Anti-virals 128.7 168.4 203.9 
Blood products    
Packed red blood cells 114.3 116.5 118.1 
Platelets 202.5 206.6 215.5 
Fresh frozen plasma 11.0 8.7 8.2 
Analgesics    
Non-opioid 261.2 270.5 279.1 
Opioid (all routes) 243.2 221.9 240.3 
PCA 18.0 19.3 22.0 
Parenteral nutrition 136.5 130.2 141.4 
Anti-hypertensives 57.4 70.3 92.5 
Diuretics 59.5 63.2 76.8 
Vasopressors    
Dopamine 7.2 7.6 9.3 
Other 12.4 13.5 16.5 
Supplemental oxygen 20.3 20.3 23.5 
Assisted ventilation 17.6 16.8 17.8 
ECMO 0.1 0.07 0.06 
Dialysis 2.2 3.2 5.5 
Imaging    
Chest X-ray 75.6 74.5 80.5 
Head CT 8.6 8.3 8.9 
Chest CT 17.4 18.0 18.5 
Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.