TABLE 3.

Competing risks regression for skeletal toxicities by age subgroup and asparaginase treatment arm

	Bone Fracture				Osteonecrosis
	Univariate		Multivariable		Univariate		Multivariable
	Hazard Ratio [95%CI]	p-value	Hazard Ratio [95%CI]	p-value	Hazard Ratio [95%CI]	p-value	Hazard Ratio [95%CI]	p-value
Age <10 Years
Hispanic vs. Non-Hispanic	0.24 [0.10–0.54]	0.0006	0.23 [0.10–0.51]	0.0003	0.61 [0.18–2.02]	0.41	0.59 [0.18–1.95]	0.39
Female vs. Male	1.25 [0.86–1.81]	0.25	1.25 [0.86–1.82]	0.23	0.35 [0.14–0.88]	0.025	0.34 [0.13–0.84]	0.020
Post induction ASP
Direct assignment vs. Not	0.96 [0.65–1.42]	0.86	0.97 [0.61–1.52]	0.88	1.92 [0.87–4.22]	0.11	1.79 [0.68–4.69]	0.23
IM E. Coli vs. Not	1.09 [0.73–1.63]	0.67	1.03 [0.64–1.67]	0.90	0.58 [0.22–1.56]	0.28	0.90 [0.27–3.01]	0.86
SR vs. Not	0.95 [0.63–1.42]	0.80	0.96 [0.64–1.43]	0.83	1.64 [0.62–4.35]	0.32	1.79 [0.68–4.71]	0.24
Obese vs. Not	1.18 [0.69–2.03]	0.55	1.42 [0.82–2.47]	0.21	0.56 [0.13–2.4]	0.43	ⱡ	ⱡ
Age ≥10 years
Hispanic vs. Non-Hispanic	0.63 [0.31–1.28]	0.20	0.62 [0.31–1.27]	0.19	0.28 [0.10–0.76]	0.013	0.23 [0.08–0.66]	0.006
Female vs. Male	0.99 [0.55–1.79]	0.98	0.91 [0.51–1.64]	0.76	0.61 [0.31–1.22]	0.16	0.49 [0.25–0.97]	0.042
Post induction ASP
Direct Assignment vs. not	0.72 [0.37–1.42]	0.35	0.80 [0.37–1.73]	0.57	0.34 [0.14–0.81]	0.015	0.32 [0.12–0.82]	0.020
IM E. Coli vs. Not	1.53 [0.85–2.73]	0.15	1.38 [0.70–2.71]	0.35	1.66 [0.88–3.11]	0.12	1.14 [0.59–2.20]	0.70
VHR vs. Not	0.77 [0.28–2.14]	0.62	0.75 [0.27–2.07]	0.58	0.41 [0.10–1.72]	0.22	ⱡ	ⱡ
Obese vs. not	1.21 [0.56–2.60]	0.63	1.31 [0.60–2.83]	0.50	0.42 [0.13–1.39]	0.16	ⱡ	ⱡ

Abbreviations: Direct assignment: Directly assigned to receive native E. Coli asparaginase IM E.Coli: Intramuscular E. Coli asparaginase; SR: Standard risk; VHR: Very high risk; ASP: asparaginase

^ⱡDue to the small number of bone events (n<4) not considered in multivariable modeling