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Prognostic impact of CLL stereotyped subsets
belonging to subset #2 should have closer clinical follow- up, and, in particular, that patients of m-subset #2 should be considered as high risk despite their formal assignment
to the M-CLL group. Correspondingly, this indicates that the BcR IG structure determined by subset assignment may be more important in determining disease biology
Table 4. Time-to-first-treatment (TTFT) Cox regression in early stage chronic lymphocytic leukemia (CLL) subset #2.
Cox regression TTFT
M-IGHV3-21 M-subset #2 U-IGHV
Yes
Yes
Univariable comparison
vs. m-IGHV vs.m-IGHV vs. m-IGHV
vs. no vs.no
Hazard ratio
IGHV analysis group
Deletion in 17p
Deletion in 11q
1.749
Leukocyte count (x109/L)
3.209
Lymphocyte doubling time
2.181
95% confidence interval Lower Upper
0.271 4.498 2.017 8.628 3.253 5.705
1.273 4.172 1.169 2.615 2.260 4.556 1.633 2.912
P
0.889 < 0.001 < 0.001
0.006
0.006 < 0.001 < 0.001
1.105 4.172 4.308
2.305
≥50 vs.<50
≤ 12 months vs. > 12 months
TTFT: time to first treatment; U: unmutated; M: mutated; IGHV: immunoglobulin heavy variable; HR: hazard ratio.
C
AB
P=0.056 P=0.050
P=0.054
D
P=0.020
P=0.001
P=0.717 P=0.059
Figure 4. Outcomes of advanced stage chronic lymphocytic leukemia (CLL) cases according to subset #2 classification and IGHV mutation. (A) Median time-to-first- treatment (TTFT) u-subset #2: 32.9 months, m-subset #2: 16.5 months, u-HV3-21: 14.2 months, m-HV3-21: 26.8 months, u-IGHV: 18.1 months, m-IGHV: 36.3 months. (B) Median time-to-next-treatment (TTNT) u-subset #2: 49.2 months, m-subset # 2: 58.7 months, u-HV3-21: 50.6 months, m-HV3-21: not reached, u-IGHV: 47.8 months, m-IGHV: not reached. (C) Median progression-free (PFS) survival u-subset #2: 21.4 months, m-subset #2: 35.5 months, u-HV3-21: 31.4 months, m- HV3-21: 57.6 months, u-IGHV: 26.7 months, m-IGHV: 54.7 months. (D) Median overall survival (OS) from diagnosis u-subset #2: not reached, m-subset #2: not reached, u-HV3-21: not reached, m-HV3-21: not reached, u-IGHV: 77.4 months, m-IGHV: not reached; Cum: cumulative.
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