Risk factors investigated for their association with leukemic progression in ET and PV: distribution in case patients who progressed to AML and control patients who did not
| Characteristic . | Cases (n = 64) . | Controls (n = 271) . | P . |
|---|---|---|---|
| ET/PV | 35 (55%)/29 (45%) | 158 (58%)/113 (42%) | |
| Age, y* | 60.5 (16-81) | 56 (13-89) | .002 |
| Sex, male/female | 27 (42%)/37 (58%) | 95 (35%)/176 (65%) | .4 |
| WBC* | 10.8 (5-29) | 8.7 (4.1-21) | < .001 |
| > 10 × 109/L | 31 (55%) | 109 (41%) | .03 |
| > 15 × 109/L | 9 (16%) | 24 (9%) | .06 |
| Abnormal karyotype | 4/29 (14%) | 11/174 (6.5%) | .5 |
| JAK2 mutation | 38/50 (76%) | 150/248 (60%) | .03 |
| JAK2 genotype (rs12340895) | |||
| CC | 24 (39%) | 92 (35%) | .8 |
| CG | 26 (42%) | 119 (45%) | |
| GG | 12 (19%) | 51 (19%) | |
| Exposure to cytoreductive agents† | |||
| No exposure | 1 (1.5%) | 60 (22%) | < .001 |
| HU only | 40 (62.5%) | 164 (60.5%) | |
| Other agents alone or in combination | 23 (36%) | 47 (17.5%) | |
| Detail of cytoreductive agents other than HU | |||
| 32P alone or in combination | 12 (19%) | 42 (16%) | .6 |
| Alkylators alone or in combination | 13 (20%) | 12 (4%) | < .001 |
| HU plus alkylators and/or 32P | 18 (28%) | 34 (12.5%) | .003 |
| Cumulated exposure to cytoreductive agents | |||
| HU cumulated dose (grams; n = 187)* | 1956 (17-6048) | 3223 (50-11882) | < .001 |
| Months on HU (n = 254)* | 68 (1.2-213) | 133 (2.8-291) | < .001 |
| Months on alkylating agents (n = 15)* | 30 (5-202) | 41 (1-164) | NC |
| 32P cumulated dose (mCi; n = 41)* | 7.0 (3.5-15.2) | 2.7 (2.3-10.8) | NC |
| DNA repair SNPs‡ | |||
| ERCC2 (XPD) Lys751Gln: CC/AA + AC (R) | 16 (25%)/47 (75%) | 25 (9%)/245 (91%) | < .001 |
| ERCC5 Asp1104His: GC + CC/GG (D) | 26 (41%)/37 (59%) | 120 (46%)/143 (54%) | .5 |
| XPC Ala499Val: TT/CC + CT (R) | 8 (14%)/50 (86%) | 18 (7%)/249 (93%) | .1 |
| XPC Lys939Gln: AC + CC/AA (D) | 36 (58%)/26 (42%) | 156 (59%)/110 (41%) | .1 |
| XRCC1 Arg399Gln: AA/GG + GA (R) | 5 (8%)/58 (92%) | 40 (15%)/228 (85%) | .2 |
| Characteristic . | Cases (n = 64) . | Controls (n = 271) . | P . |
|---|---|---|---|
| ET/PV | 35 (55%)/29 (45%) | 158 (58%)/113 (42%) | |
| Age, y* | 60.5 (16-81) | 56 (13-89) | .002 |
| Sex, male/female | 27 (42%)/37 (58%) | 95 (35%)/176 (65%) | .4 |
| WBC* | 10.8 (5-29) | 8.7 (4.1-21) | < .001 |
| > 10 × 109/L | 31 (55%) | 109 (41%) | .03 |
| > 15 × 109/L | 9 (16%) | 24 (9%) | .06 |
| Abnormal karyotype | 4/29 (14%) | 11/174 (6.5%) | .5 |
| JAK2 mutation | 38/50 (76%) | 150/248 (60%) | .03 |
| JAK2 genotype (rs12340895) | |||
| CC | 24 (39%) | 92 (35%) | .8 |
| CG | 26 (42%) | 119 (45%) | |
| GG | 12 (19%) | 51 (19%) | |
| Exposure to cytoreductive agents† | |||
| No exposure | 1 (1.5%) | 60 (22%) | < .001 |
| HU only | 40 (62.5%) | 164 (60.5%) | |
| Other agents alone or in combination | 23 (36%) | 47 (17.5%) | |
| Detail of cytoreductive agents other than HU | |||
| 32P alone or in combination | 12 (19%) | 42 (16%) | .6 |
| Alkylators alone or in combination | 13 (20%) | 12 (4%) | < .001 |
| HU plus alkylators and/or 32P | 18 (28%) | 34 (12.5%) | .003 |
| Cumulated exposure to cytoreductive agents | |||
| HU cumulated dose (grams; n = 187)* | 1956 (17-6048) | 3223 (50-11882) | < .001 |
| Months on HU (n = 254)* | 68 (1.2-213) | 133 (2.8-291) | < .001 |
| Months on alkylating agents (n = 15)* | 30 (5-202) | 41 (1-164) | NC |
| 32P cumulated dose (mCi; n = 41)* | 7.0 (3.5-15.2) | 2.7 (2.3-10.8) | NC |
| DNA repair SNPs‡ | |||
| ERCC2 (XPD) Lys751Gln: CC/AA + AC (R) | 16 (25%)/47 (75%) | 25 (9%)/245 (91%) | < .001 |
| ERCC5 Asp1104His: GC + CC/GG (D) | 26 (41%)/37 (59%) | 120 (46%)/143 (54%) | .5 |
| XPC Ala499Val: TT/CC + CT (R) | 8 (14%)/50 (86%) | 18 (7%)/249 (93%) | .1 |
| XPC Lys939Gln: AC + CC/AA (D) | 36 (58%)/26 (42%) | 156 (59%)/110 (41%) | .1 |
| XRCC1 Arg399Gln: AA/GG + GA (R) | 5 (8%)/58 (92%) | 40 (15%)/228 (85%) | .2 |
NC indicates not computable in the framework of a matched case-control design because of the insufficient number of patients with this feature.
Median (range).
Patients who received IFN or anagrelide as the only cytoreductive drugs were included in the “no exposure” group.
Results from the best inheritance model for each specific polymorphism. Genetic models: R indicates recessive; and D, dominant.