Prognostic factors and outcomes of infant acute lymphoblastic leukemia (ALL), hypodiploid ALL, and mixed-phenotype acute leukemia (MPAL) in Canada: a report from CYP-C

Figures & data

Table 1. Baseline patient characteristics.

Baseline characteristics	Total (n = 227)	ALL subtypes			p-value
		Infant ALL (n = 139)	Hypodiploid (n = 43)	MPAL (n = 45)
Age
Median age [IQR]		7.0 [4.0–10.0] months	7.0 [3.0–14.0] years	7.0 [4.0–12.0] years
Age ≤ 3 months (%)		31 (22.3)
3–6 months (%)		35 (25.2)
6–9 months (%)		36 (25.9)
9–12 months (%)		37 (26.6)
White blood cell (WBC) count at diagnosis
Median WBC [IQR]	41.0 [10.2–182.6]	105.5 [23.8–358.1]	12.8 [5.0–26.1]	12.9 [3.8–54.4]	<0.001
National Cancer Institute (NCI) risk status (n = 88)					<0.001
Standard risk (%)	35 (39.8)		18 (41.9)	17 (37.8)
High risk (%)	48 (54.5)		24 (55.8)	24 (53.3)
Sex					0.751
Male (%)	117 (51.5)	69 (49.6)	24 (55.8)	24 (53.3)
Female (%)	110 (48.5)	70 (50.4)	19 (44.2)	21 (46.7)
Ethnicity					0.964
Caucasian (%)	121 (53.3)	66 (47.5)	30 (69.8)	25 (55.6)
Asian (%)	31 (13.7)	19 (13.7)	6 (14.0)	6 (13.3)
Other (%)	33 (14.5)	22 (15.8)	6 (13.9)	5 (11.1)
Central nervous system (CNS) status					0.001
CNS-1 (%)	120 (52.9)	65 (46.8)	36 (83.7)	19 (42.2)
CNS-2 (%)	56 (24.7)	44 (31.7)	6 (14.0)	6 (13.3)
CNS-3 (%)	25 (11.0)	22 (15.8)	*	*
Not available (%)	26 (11.5)	8 (5.8)	*	*
Testicular involvement (n = 117)					0.122
Yes (%)	6 (5.1)	6 (8.7)	0	0
No (%)	55 (47.0)	28 (40.6)	15 (62.5)	12 (50.0)
Not available (%)	56 (47.9)	35 (50.7)	9 (37.5)	12 (50.0)
Cytogenetics
Favorable (%)	15 (6.6)	12 (8.6)	0	*	0.685
Unfavorable (%)	108 (47.6)	59 (42.4)	43 (100)	6 (13.3)	<0.001
Not available (%)	104 (45.8)	68 (48.9)	0	*
Enrolled on a clinical trial?					<0.001
Yes (%)	76 (33.5)	50 (36.0)	23 (53.5)	5 (11.1)
No (%)	147 (64.8)	86 (61.9)	20 (46.5)	41 (91.1)
Treatment start					0.003
Before 2010 (%)	109 (48.0)	58 (41.7)	31 (72.1)	20 (44.4)
After 2010 (%)	114 (50.2)	78 (56.1)	12 (27.9)	24 (53.3)
Hematopoietic stem cell transplant					0.002
Prior to first relapse (%)	42 (18.5)	16 (11.5)	11 (25.6)	15 (33.3)
Not prior to first relapse (%)	185 (81.5)	123 (88.5)	32 (74.4)	30 (66.7)

*Cells with values that are >0 but <5 and adjacent cells have been suppressed as per the CYP-C Data Access and Publications Guidelines to prevent residual disclosure.

Figure 1. (A) Event-free survival and (B) overall survival of the entire cohort. (C) Event-free survival and (D) overall survival by subtype.

Table 2. Univariate and multivariable hazard models for event-free survival in infant acute lymphoblastic leukemia (ALL), hypodiploid ALL, mixed-phenotype acute leukemia (MPAL) and the entire cohort.

	Univariate		Multivariable
	Hazard Ratio [95% Confidence Interval]	p-value	Hazard Ratio [95% Confidence Interval]	p-value
Entire cohort
Age ≥ 10 years	0.98 [0.94–1.11]	0.293
Male sex	1.27 [0.86–1.87]	0.225
White blood cell ≥ 50 × 10^9/L	2.25 [1.53–3.31]	<0.001	2.40 [1.58–3.63]	<0.001
Central nervous system-3	1.66 [0.90–3.05]	0.102	1.58 [0.86–2.90]	0.142
Caucasian	1.02 [0.63–1.60]	0.927
Favorable cytogenetics	0.99 [0.53–1.87]	0.977
Unfavorable cytogenetics	1.65 [0.75–3.64]	0.212
Enrolled on a clinical trial	1.07 [0.72–1.61]	0.727
Treatment after 2010	0.90 [0.61–1.33]	0.597
Hematopoietic stem cell transplant prior to first relapse	1.02 [0.63–1.64]	0.948
Infant ALL
Age < 3 months	3.49 [2.13–5.74]	<0.001	4.01 [1.75–9.15]	0.001
Age 3–6 months	0.48 [0.27–0.85]	0.012
Age 6–9 months	0.21 [0.11–0.42]	<0.001
Age 9–12 months	0.20 [0.10–0.39]	<0.001
Male sex	1.41 [0.89–2.22]	0.144	1.20 [0.62–2.34]	0.582
White blood cell ≥ 100 × 10^9/L	2.29 [1.44–3.64]	0.001	3.85 [1.68–8.83]	0.002
Central nervous system-3	1.70 [0.91–3.18]	0.094	1.50 [0.61–3.72]	0.381
Caucasian	1.00 [0.59–1.69]	0.990
Favorable cytogenetics	0.79 [0.33–1.88]	0.597
Enrolled on a clinical trial	1.02 [0.64–1.62]	0.950
Treatment after 2010	0.87 [0.55–1.38]	0.550
Hematopoietic stem cell transplant prior to first relapse	1.29 [0.64–2.60]	0.475
Hypodiploid ALL
Age ≥ 10 years	2.01 [0.65–6.16]	0.223
Male sex	1.93 [0.59–6.26]	0.276
White blood cell ≥ 50 × 10^9/L	0.63 [0.08–4.85]	0.656
White blood cell ≥ 100 × 10^9/L	0.70 [0.09–5.36]	0.727
Caucasian	0.62 [0.20–1.90]	0.401
Favorable cytogenetics	1.56 [0.48–5.08]	0.458
Enrolled on a clinical trial	0.60 [0.20–1.80]	0.366
Treatment after 2010	0.88 [0.19–4.05]	0.870
Hematopoietic stem cell transplant prior to first relapse	1.76 [0.58–5.39]	0.321
MPAL
Age ≥ 10 years	4.13 [1.45–11.74]	0.008	5.77 [0.98–34.11]	0.053
Male sex	0.81 [0.31–2.10]	0.662
White blood cell ≥ 50 × 10^9/L	1.03 [0.34–3.16]	0.959
White blood cell ≥ 100 × 10^9/L	0.85 [0.19–3.73]	0.831
Favorable cytogenetics	2.25 [0.37–13.62]	0.378
Unfavorable cytogenetics	1.47 [0.24–8.90]	0.673
Enrolled on a clinical trial	5.93 [1.64–21.38]	0.007	13.50 [1.24–146.71]	0.033
Treatment after 2010	0.30 [0.10–0.95]	0.040	0.21 [0.03–1.42]	0.110
Hematopoietic stem cell transplant prior to first relapse	1.27 [0.48–3.37]	0.625
Acute myeloid leukemia-directed induction	1.97 [0.61–6.41]	0.259
Acute myeloid leukemia-directed overall treatment	4.09 [1.33–12.55]	0.014	29.10 [3.38–250.39]	0.002

The bold values are predictors of outcome that met statistical significance in the univariate or multivariable analysis as per our definition in the Methods.

Table 3. Univariate and multivariable hazard models of overall survival in infant acute lymphoblastic leukemia (ALL), hypodiploid ALL, mixed-phenotype acute leukemia (MPAL) and the entire cohort.

	Univariate		Multivariable
	Hazard Ratio [95% confidence interval]	p value	Hazard Ratio [95% confidence interval]	p-value
Entire cohort
Age ≥ 10 years	0.10 [0.95–1.04]	0.880
Male sex	1.34 [0.843–2.13]	0.216
White blood cell ≥ 50 × 10^9/L	1.85 [1.17–2.93]	0.009	2.48 [1.27–4.82]	0.008
Central nervous system-3	2.01 [1.02–3.97]	0.043	2.58 [0.58–6.21]	0.034
Caucasian	1.10 [0.64–1.90]	0.741
Favorable cytogenetics	0.57 [0.24–1.34]	0.196	1.08 [0.37–3.09]	0.892
Unfavorable cytogenetics	3.42 [1.06–11.09]	0.040	3.95 [0.81–19.14]	0.088
Enrolled on a clinical trial	1.09 [0.68–1.77]	0.713
Treatment after 2010	0.69 [0.43–1.12]	0.135	0.95 [0.47–1.94]	0.894
Hematopoietic stem cell transplant prior to first relapse	1.13 [0.65–1.96]	0.671
Infant ALL
Age < 3 months	4.19 [2.39–7.36]	<0.001	4.51 [1.81–11.27]	0.001
Age 3–6 months	0.41 [0.21–0.78]	0.007
Age 6–9 months	0.18 [0.08–0.42]	<0.001
Age 9–12 months	0.15 [0.06–0.35]	<0.001
Male sex	1.37 [0.79–2.37]	0.258
White blood cell ≥ 100 × 10^9/L	2.18 [1.25–3.82]	0.006	3.39 [1.34–8.56]	0.010
Central nervous system-3	2.08 [1.03–4.20]	0.041	1.41 [0.51–3.92]	0.505
Caucasian	0.88 [0.47–1.64]	0.678
Favorable cytogenetics	0.54 [0.19–1.57]	0.258
Enrolled on a clinical trial	1.10 [0.63–1.93]	0.727
Treatment after 2010	0.62 [036–1.08]	0.092	0.96 [0.41–2.22]	0.917
Hematopoietic stem cell transplant prior to first relapse	1.47 [0.69–3.12]	0.322
Hypodiploid ALL
Age ≥ 10 years	1.87 [0.53–6.63]	0.334
Male sex	1.88 [0.49–7.30]	0.360
White blood cell ≥ 50 × 10^9/L	0.90 [0.11–7.11]	0.920
White blood cell ≥ 100 × 10^9/L	0.95 [0.12–7.48]	0.959
Caucasian	0.99 [0.25–3.83]	0.985
Favorable cytogenetics	0.37 [0.05–2.90]	0.342
Enrolled on a clinical trial	0.45 [0.13–1.61]	0.220
Treatment after 2010	1.77 [0.36–8.77]	0.487
Hematopoietic stem cell transplant prior to first relapse	1.75 [0.49–6.23]	0.389
MPAL
Age ≥ 10 years	6.93 [1.50–32.11]	0.013	4.69 [0.70–31.47]	0.112
Male sex	1.18 [0.36–3.90]	0.783
White blood cell ≥ 50 × 10^9/L	0.35 [0.04–2.70]	0.311
Favorable cytogenetics	3.27 [0.20–52.97]	0.405
Unfavorable cytogenetics	0.75 [0.05–11.97]	0.836
Enrolled on a clinical trial	4.80 [0.99–23.23]	0.051	6.83 [0.72–64.47]	0.093
Treatment after 2010	0.24 [0.05–1.16]	0.075	0.18 [0.02–1.82]	0.148
Hematopoietic stem cell transplant prior to first relapse	1.04 [0.30–3.59]	0.948
Acute myeloid leukemia-directed induction	1.40 [0.28–6.93]	0.683
Acute myeloid leukemia-directed overall treatment	5.66 [1.22–26.26]	0.027	22.88 [2.53–207.10]	0.005

The bold values are predictors of outcome that met statistical significance in the univariate or multivariable analysis as per our definition in the Methods.

Data availability statement

Data used in this publication are from the Cancer in Young People in Canada Surveillance Program and are used with the permission of the Public Health Agency of Canada.