Supplementary Table 1.
Pre-treatment variables.
N
Age (y) (median [range])
Male N (%)
CP duration mo (median [range])
Prior hydroxyurea >1 mo N (%)
Prior interferon-α N (%)
Splenomegaly N (%)
WBC X10E9/L (median [range])
Hemoglobin g/L (median [range])
Platelets x10E9/L (median [range])
Blood blasts % (median [range])
Blood basophils % (median [range])
Bone marrow blasts % (median [range])
Sokal score N (%)
Low-risk
Intermediate-risk
High-risk
Unknown
Median follow-up survivors mo (range)
Imatinib
172
38 (14–55)
125 (73)
1 (0–11)
44 (26)
14 (8)
62 (36)
18.1 (3.2–533)
123 (55–172)
298 (45–1904)
0 (0–4)
4 (0–18)
0.5 (0–10)
Transplant
176
37 (12–53)
136 (77)
5 (0–11)
161 (92)
36 (21)
31 (18)
6.6 (1–45)
130 (68–182)
222 (16–1936)
0 (0–7)
3 (0–19)
1.5 (0–8)
0.077
0.323
<0.0001
<0.001
0.001
<0.0001
<0.0001
0.018
<0.0001
0.045
<0.0001
0.509
102 (59)
44 (26)
12 (7)
14 (8)
49 (12–143)
108 (61)
32 (18)
10 (6)
26 (15)
82 (32–137)
0.694
0.095
0.620
0.052
<0.0001
CP, chronic phase.
1
P-value
Supplementary Table 2. Relative risks of event (1-EFS), treatment-failure (1-PFS) and
death (1-survival). (Left-truncation method)*
N
RR (95% CI)
P-value
1-EFS
Main effect
Imatinib
172
1.0
Transplant
176
3.6 (2.0–6.8)
<0.0001
Other
Blood basophils < 5
228
1.0
≥5
120
2.2 (1.3– 3.9)
0.0043
Blood blasts No
300
1.00
Yes
48
2.2 (1.1–4.3)
0.0232
1-PFS
Main effect
Imatinib
172
1.0
Transplant
176
5.3 (2.4–11.7)
<0.0001
Other
Blood basophils < 5
228
1.0
≥5
120
2.3 (1.2–4.3)
0.0109
Death
Main effect
Imatinib
172
1.0
Transplant
176
42 (6–309)
0.0003
Other
Blood basophils < 5
228
1.0
≥5
120
2.2 (1.1–4.4)
0.0281
* Left-truncated Cox proportional hazards regression models were used to evaluate the
relative risk of subjects receiving imatinib versus a transplant. Variables considered in
the multivariate models were: age (≥40 versus <40 years); subject gender (male versus
female); splenomegaly (yes versus no); WBC (≥30 vs <30×10E9/L); hemoglobin
concentration (<120 versus ≥120 g/L); platelet level (<450 versus ≥450×10E9/L); blood
blasts (no versus yes); blood basophils (<5% versus ≥5%); bone marrow blasts (<5%
versus ≥5%; and Sokal score (unknown versus 1 versus 2 versus 3; 25).
The assumption of proportional hazards for each variable in the Cox model was
tested using time-dependent covariates.
Figures and tests showed there is no
statistical evidence proportionality assumptions did not hold.
2
A backward stepwise
model selection approach was used to identify all significant risk factors. Each step of
model building contained the main effect for imatinib versus transplant and risk factors
significant at a P≤0.05 level were retained in the final model. Potential interactions
between main effect (imatinib versus transplant) and all significant risk factors were
tested; no interaction was detected. Adjusted probabilities of EFS, PFS and survival
were generated from the final Cox models stratified on treatment with imatinib or
transplant, and weighted averages of covariate values using the pooled sample
proportion as the weight function. These adjusted probabilities estimate likelihood of
outcomes in populations with similar prognostic factors.
RR, relative risk;
EFS, event-free survival;
3
PFS, progression-free survival.
Supplementary Table 3.
(Not-left-truncation method)
Outcome:
EFS: 2 Year
4 Year
6 Year
8 Year
10 Year
PFS: 2 Year
4 Year
6 Year
8 Year
10 Year
OS: 2 Year
4 Year
6 Year
8 Year
10 Year
Adjusted probabilities of EFS, PFS and survival
Imatinib
At Risk
P (95% CI)
153
93 (88 – 96)%
81
92 (87 – 95)%
33
92 (87 – 95)%
12
92 (87 – 95)%
8
92 (87 – 95)%
157
96 (92 – 98)%
86
96 (91 – 98)%
37
96 (91 – 98)%
15
96 (91 – 98)%
11
96 (91 – 98)%
158
99 (96 – 100)%
87
99 (96 – 100)%
37
99 (96 – 100)%
15
99 (96 – 100)%
11
99 (96 – 100)%
EFS, event-free survival;
Transplant
At Risk
P (95% CI)
144
79 (72 – 84)%
122
77 (70 – 83)%
93
76 (69 – 82)%
38
75 (67 – 81)%
17
75 (67 – 81)%
151
84 (77 – 89)%
126
81 (74 – 86)%
95
80 (73 – 85)%
39
78 (70 – 84)%
17
78 (70 – 84)%
151
84 (77 – 89)%
127
81 (74 – 87)%
96
81 (73 – 86)%
40
79 (71 – 85)%
18
79 (71 – 85)%
PFS, progression-free survival.
4
P
0.0003
0.0002
0.0001
0.0001
0.0001
0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
<0.0001
Supplementary Table 4. Relative risks of event (1-EFS), treatment-failure (1-PFS) and
death (1-survival). (Not-Left-truncation method)
Outcome event
1-EFS:
Main Effect: Imatinib
Transplant
Other Risk factor:
Blood basophiles < 5
≥5
Blood blast No
Yes
1-PFS:
Main Effect:
Imatinib
Transplant
Other Risk factor:
Blood basophiles < 5
≥5
Overall Mortality:
Main Effect: Imatinib
Transplant
Other Risk factor:
Blood basophiles < 5
≥5
RR, relative risk;
N
RR (95% CI)
P
172
176
1.00
3.09 (1.68 – 5.69)
0.0003
228
120
300
48
1.00
2.25 (1.30 – 3.90)
1.00
2.16 (1.10 – 4.23)
172
176
1.00
4.91 (2.23 – 10.83)
<0.0001
228
120
1.00
2.31 (1.23 – 4.33)
0.0095
172
176
1.00
37.86 (5.13 – 279)
0.0004
228
120
1.00
2.23 (1.10 – 4.49)
0.0256
EFS, event-free survival;
5
0.0040
0.0254
PFS, progression-free survival.
Supplementary Table 5.
Left-truncated analysis results (truncated at time of imatinib or
transplant)
N
RR (95% CI)
P
Outcome event
1-PFS:
Main Effect:
Imatinib
Transplant
Other Risk factor:
Blood basophiles < 5
≥5
1-EFS:
Main Effect: Imatinib
Transplant
Other Risk factor:
Blood basophiles < 5
≥5
Blood blast No
Yes
Overall Mortality:
Main Effect: Imatinib
Transplant
Other Risk factor:
Blood basophiles < 5
≥5
RR, relative risk;
172
176
1.00
5.38 (2.44 – 11.88)
<0.0001
228
120
1.00
2.27 (1.21 – 4.28)
0.0108
172
176
1.00
3.61 (1.94 – 6.71)
<0.0001
228
120
300
48
1.00
2.23 (1.29 – 3.88)
1.00
2.20 (1.12 – 4.32)
172
176
1.00
14.47 (4.37 – 47.96)
<0.0001
228
120
1.00
2.41 (1.23 – 4.75)
0.0109
EFS, event-free survival;
6
0.0044
0.0226
PFS, progression-free survival.
Supplementary Table 6.
Outcome event
1-PFS:
Main Effect:
Imatinib
Transplant
Other Risk factor:
Blood basophiles < 5
≥5
1-EFS:
Main Effect: Imatinib
Transplant
Other Risk factor:
Blood basophiles < 5
≥5
Blood blast
No
Yes
Overall Mortality:
Main Effect: Imatinib
Transplant
Other Risk factor:
Blood basophiles < 5
≥5
RR, relative risk;
Not-Left-truncated analysis results (truncated at time of
imatinib or transplant)
N
RR (95% CI)
P
172
176
1.00
4.99 (2.26 – 11.00)
<0.0001
228
120
1.00
2.31 (1.23 – 4.33)
0.0095
172
176
1.00
3.09 (1.68 – 5.69)
0.0003
228
120
300
48
1.00
2.24 (1.29 – 3.89)
1.00
2.16 (1.10 – 4.24)
172
176
1.00
13.21 (3.99 – 43.71)
<0.0001
228
120
1.00
2.44 (1.24 – 4.81)
0.0097
EFS, event-free survival;
7
0.0041
0.0248
PFS, progression-free survival.
Supplementary Figure 1.
CONSORT diagram.
TRM, treatment-related mortality;
TKI, tyrosine kinase inhibitor; NR: no response;
CHR, complete hematological response.
8
Supplementary Figure 2.
Adjusted probabilities of EFS, PFS and survival from
diagnosis (Not-Left-truncation method).
EFS, event-free survival;
A: EFS;
B: PFS;
PFS, progression-free survival.
9
C: Survival.