Introduction: Children with Down syndrome (DS) and acute lymphoid leukemia (ALL) have inferior outcomes due to increased treatment-related toxicity. In 2005 and 2006, multiple clinical trial protocols were modified to increase supportive care measures for these children; however, national supportive care utilization patterns for these patients have not been subsequently evaluated.

Methods: A validated retrospective cohort of pediatric patients with ALL admitted from 1999 to 2011 was assembled from the Pediatric Health Information System (PHIS) database to examine organ toxicity, sepsis, and resource utilization in children with and without DS. A sub-analysis of mortality in children with DS ALL before and after the 2006 supportive care recommendation was also conducted.

Results: 10699 patients with ALL were identified; 298 of these children had DS ALL (2.8%). Children with DS ALL had a significantly higher percentage of patients who were female (52% vs. 44%, p = 0.003), white (83% vs. 75%, p = 0.005), publically insured (48% vs. 38%, p = 0.002), and who had a congenital cardiac abnormality (26% vs. 2%, p < 0.0001). DS was associated with an increased risk of cardiovascular failure (OR 2.0, 95% CI 1.6-2.7), respiratory failure (OR 2.1, 95% CI: 1.6-2.9) and sepsis (OR 1.8, 95% CI: 1.4-2.4) in adjusted analyses (Table 1). Children with DS ALL had significantly greater utilization of antibiotics indicated for gram-positive infections, quinolones, azoles, supplemental oxygen, and ventilation, as well as significantly less utilization of opiate and non-opiate analgesics, PCAs, and antiemetics compared to children with non-DS ALL. Cardiac failure and sepsis rates were decreased in all children diagnosed after 2006 (OR 0.8, CI: 0.8-0.9, and OR 0.7, CI: 0.6-0.7, respectively). Children with DS ALL demonstrated a non-significant decrease in mortality after the 2006 guideline implementation (6.6% to 2.8%, p=0.116).

Conclusion: In conclusion, children with DS ALL have significantly increased cardiac, respiratory, and infectious toxicity. The elevated antibiotic and antifungal usage in children with DS ALL and trend towards mortality decrease may suggest successful implementation of supportive care measures; however, decreased analgesic and antiemetic use may suggest other unmet supportive care needs in these patients.

Table
Table 1. Adjusted analyses of organ failure by Down syndrome status, demographics, congenital cardiac defects, and year of admission. 
 Cardiovascular
Failure
OR (95% CI) 		Respiratory
Failure
OR (95% CI) 		Sepsis
OR (95% CI) 		Neurologic
Failure
OR (95% CI) 		Liver
Failure
OR (95% CI) 
Down syndrome 2.0
(1.6-2.7)*** 		2.1
(1.6-2.9)*** 		1.8
(1.4-2.4)*** 		3.4
(1.9-6.2)*** 		1.4
(1.0-1.9)* 
Age      
< 1 yr. 4.5
(3.5-5.8)*** 		7.4
(5.7-9.7)*** 		8.3
(4.9-8.2)*** 		1.4
(0.6-3.3) 		1.9
(1.4-2.5)*** 
³ 1 yr. and < 5 yrs. 0.7
(0.6-0.7)*** 		0.7
(0.6-0.8)*** 		0.9
(0.7-1.0)* 		0.4
(0.3-0.7)** 		1.0
(0.8-1.1) 
³ 5 yrs. and < 10 yrs. - - - - - 
³ 10 yrs. and < 15 yrs. 2.2
(1.9-2.5)*** 		1.8
(1.5-2.1)*** 		1.7
(1.4-1.9)*** 		2.1
(1.4-3.2)** 		1.4
(1.2-1.6)*** 
³ 15 yrs. 2.4
(2.0-2.8)*** 		2.2
(1.8-2.7)*** 		2.0
(1.6-2.3)*** 		2.7
(1.7-1.2)*** 		1.7
(1.4-2.0)*** 
Race      
Non-Whitea 0.9
(0.8-1.0) 		1.1
(0.9-1.2) 		1.0
(0.9-1.2) 		1.4
(1.0-2.0)* 		0.8
(0.7-0.9)** 
White - -  - - 
Insurance      
Publicb 1.3
(1.1-1.4)*** 		1.2
(1.1-1.4)** 		1.5
(1.3-1.6)*** 		1.3
(0.9-1.9) 		1.0
(0.9-1.1) 
Otherc 1.2
(1.0-1.3)* 		0.8
(0.7-1.0)* 		1.0
(0.9-1.1) 		1.5
(1.0-2.3)* 		1.0
(0.8-1.1) 
Private - -  - - 
Gender      
Female 1.1
(1.0-1.2)* 		1.0
(0.9-1.1) 		1.2
(1.1-1.3)** 		1.0
(0.7-1.3) 		1.1
(1.0-1.2) 
Male - - - -  
Congenital Cardiac Defectd 1.6
(1.2-2.1)** 		1.5
(1.1-2.1)** 		1.3
(0.9-1.7) 		1.7
(0.8-3.4) 		1.1
(0.8-1.6) 
Diagnosis in 2006-2011 0.8
(0.8-0.9)** 		1.0
(0.9-1.2) 		0.7
(0.6-0.7)*** 		0.8
(0.6-1.0) 		1.0
(0.9-1.1) 
a Non-white includes Black, Asian/Pacific Islander, American Indian, Other, and Unknown.
bPublic includes Medicaid, Medicare, other government, and Title V.
cOther includes Self-pay, Other, and Unknown.
d Congenital cardiac defect was defined by ICD-9 codes as described in supplemental table 1.
*** p < 0.001; ** p < 0.01; * p < 0.05. 
Table 1. Adjusted analyses of organ failure by Down syndrome status, demographics, congenital cardiac defects, and year of admission. 
 Cardiovascular
Failure
OR (95% CI) 		Respiratory
Failure
OR (95% CI) 		Sepsis
OR (95% CI) 		Neurologic
Failure
OR (95% CI) 		Liver
Failure
OR (95% CI) 
Down syndrome 2.0
(1.6-2.7)*** 		2.1
(1.6-2.9)*** 		1.8
(1.4-2.4)*** 		3.4
(1.9-6.2)*** 		1.4
(1.0-1.9)* 
Age      
< 1 yr. 4.5
(3.5-5.8)*** 		7.4
(5.7-9.7)*** 		8.3
(4.9-8.2)*** 		1.4
(0.6-3.3) 		1.9
(1.4-2.5)*** 
³ 1 yr. and < 5 yrs. 0.7
(0.6-0.7)*** 		0.7
(0.6-0.8)*** 		0.9
(0.7-1.0)* 		0.4
(0.3-0.7)** 		1.0
(0.8-1.1) 
³ 5 yrs. and < 10 yrs. - - - - - 
³ 10 yrs. and < 15 yrs. 2.2
(1.9-2.5)*** 		1.8
(1.5-2.1)*** 		1.7
(1.4-1.9)*** 		2.1
(1.4-3.2)** 		1.4
(1.2-1.6)*** 
³ 15 yrs. 2.4
(2.0-2.8)*** 		2.2
(1.8-2.7)*** 		2.0
(1.6-2.3)*** 		2.7
(1.7-1.2)*** 		1.7
(1.4-2.0)*** 
Race      
Non-Whitea 0.9
(0.8-1.0) 		1.1
(0.9-1.2) 		1.0
(0.9-1.2) 		1.4
(1.0-2.0)* 		0.8
(0.7-0.9)** 
White - -  - - 
Insurance      
Publicb 1.3
(1.1-1.4)*** 		1.2
(1.1-1.4)** 		1.5
(1.3-1.6)*** 		1.3
(0.9-1.9) 		1.0
(0.9-1.1) 
Otherc 1.2
(1.0-1.3)* 		0.8
(0.7-1.0)* 		1.0
(0.9-1.1) 		1.5
(1.0-2.3)* 		1.0
(0.8-1.1) 
Private - -  - - 
Gender      
Female 1.1
(1.0-1.2)* 		1.0
(0.9-1.1) 		1.2
(1.1-1.3)** 		1.0
(0.7-1.3) 		1.1
(1.0-1.2) 
Male - - - -  
Congenital Cardiac Defectd 1.6
(1.2-2.1)** 		1.5
(1.1-2.1)** 		1.3
(0.9-1.7) 		1.7
(0.8-3.4) 		1.1
(0.8-1.6) 
Diagnosis in 2006-2011 0.8
(0.8-0.9)** 		1.0
(0.9-1.2) 		0.7
(0.6-0.7)*** 		0.8
(0.6-1.0) 		1.0
(0.9-1.1) 
a Non-white includes Black, Asian/Pacific Islander, American Indian, Other, and Unknown.
bPublic includes Medicaid, Medicare, other government, and Title V.
cOther includes Self-pay, Other, and Unknown.
d Congenital cardiac defect was defined by ICD-9 codes as described in supplemental table 1.
*** p < 0.001; ** p < 0.01; * p < 0.05. 
View Large

Disclosures

No relevant conflicts of interest to declare.

Topics:
acute lymphocytic leukemia, child, down syndrome, pediatrics, supportive care, toxic effect, congenital heart defects, sepsis, analgesics, antibiotics

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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