Table 2.
Clinical and laboratory characteristics of 641 patients with primary myelofibrosis stratified by the revised cytogenetic risk modela
| Variables | All patients (n = 641)b | Very high risk karyotype (n = 43) | Unfavorable karyotype (n = 94) | Favorable karyotype (n = 504) | P-value |
|---|---|---|---|---|---|
| Age in years; median (range) | 63 (19–89) | 65 (46–87) | 64 (38–81) | 62 (19–89) | 0.02 |
| Age >65 years; n (%) | 263 (41) | 22 (51) | 38 (40) | 203 (40) | 0.4 |
| Males (%) | 411 (64) | 26 (60) | 67 (71) | 318 (63) | 0.3 |
| Hemoglobin <10 g/dl; n (%) | 260 (41) | 28 (65) | 42 (45) | 190 (38) | 0.001 |
| Transfusion requiring; n (%) | 191 (30) | 25 (58) | 30 (32) | 136 (27) | <0.001 |
| Leukocytes, x109/l; median (range) | 9 (1–219) | 10 (2–75) | 8 (1.4–219) | 9.2 (1–176) | 0.5 |
| Leukocytes >25 × 109/l; n (%) | 89 (14) | 9 (23) | 14 (15) | 66 (13) | 0.2 |
| Platelets, x109/l; median (range) | 237 (10–2466) | 123.5 (11–1000) | 154 (10–2282) | 261 (12–2466) | <0.001 |
| Platelets <100 × 109/l; n (%) | 122 (19) | 18 (45) | 24 (26) | 80 (16) | <0.001 |
| Circulating blasts ≥1%; n (%) | 297 (47) | 29 (71) | 49 (54) | 219 (44) | 0.001 |
| Circulating blasts ≥2%; n (%) | 173 (27) | 23 (53) | 29 (31) | 121 (24) | <0.001 |
| Constitutional symptoms; n (%) | 208 (32) | 19 (44) | 36 (38) | 153 (30) | 0.07 |
| DIPSS c risk distribution | <0.001 | ||||
| High; n (%) | 83 (13) | 14 (33) | 14 (15) | 55 (11) | |
| Intermediate-2; n (%) | 242 (38) | 24 (56) | 36 (38) | 182 (36) | |
| Intermediate-1 n (%) | 214 (33) | 3 (7) | 35 (37) | 176 (35) | |
| Low; n (%) | 102 (16) | 2 (4) | 9 (10) | 91 (18) | |
| Driver mutations | 0.14 | ||||
| JAK2; n (%) | 368 (57) | 21 (49) | 56 (60) | 291 (57) | |
| CALR type 1/like; n (%) | 123 (19) | 6 (14) | 23 (24) | 94 (19) | |
| CALR type 2/like; n (%) | 32 (5) | 3 (7) | 2 (2) | 27 (5) | |
| MPL; n (%) | 46 (7) | 3 (7) | 4 (4) | 39 (8) | |
| Triple negative; n (%) | 72 (12) | 10 (23) | 9 (10) | 53 (11) | |
| ASXL1-mutated; n (%) | 242 (38) | 24 (56) | 35 (37) | 183 (36) | 0.04 |
| SRSF2-mutated; n (%) | 89 (14) | 12 (28) | 9 (10) | 68 (13) | 0.01 |
| U2AF1Q157-mutated; n (%) | 50 (8) | 2 (5) | 7 (7) | 41 (8) | 0.7 |
| EZH2-mutated; n (%) | 37 (7) | 3 (8) | 4 (5) | 30 (7) | 0.7 |
| IDH1/2-mutated; n (%) | 23 (4) | 2 (5) | 3 (4) | 18 (4) | 0.9 |
| MIPSS70-plus d risk distribution | <0.001 | ||||
| Very high; n (%) | 76 (12) | 33 (77) | 37 (39) | 6 (1) | |
| High; n (%) | 263 (41) | 10 (23) | 53 (57) | 200 (40) | |
| Intermediate; n (%) | 125 (20) | 0 (0) | 4 (4) | 121 (24) | |
| Low; n (%) | 177 (27) | 0 (0) | 0 (0) | 177 (35) |
The values in bold indicate a significant P-value (<0.05)
ASXL1 additional sex combs like 1, SRSF2 serine/arginine-rich splicing factor 2, U2AF1 U2small nuclear RNA auxiliary factor 1, EZH2 enhancer of zeste homolog 2, IDH1/2 isocitrate dehydrogenase 1/2, JAK2 Janus kinase 2, CALR calreticulin, MPL myeloproliferative leukemia virus oncogene
a Revised cytogenetic risk stratification: “very high risk (VHR)”—single/multiple abnormalities of −7, i(17q), inv(3)/3q21, 12p−/12p11.2, 11q−/11q23, +21, or other autosomal trisomies, not including +8/+9; “favorable”—normal karyotype or sole abnormalities of 13q−, +9, 20q−, chromosome 1 translocation/duplication or sex chromosome abnormality including—Y; “unfavorable”—all other abnormalities (reference in the text)
b In most instances, including all GIPSS-relevant variables, information was available in all 641 patients. In all instances of genetic risk factor analysis, a minimum of 500 informative cases was required and missing information did not exceed 10%
c DIPSS, Dynamic International Prognostic Scoring System uses five independent predictors of inferior survival: age >65 years, hemoglobin <10 g/dl, leukocytes >25 × 109/L, circulating blasts ≥1% and constitutional symptoms (reference in the text)
d MIPSS70-plus, Mutation-Enhanced International Prognostic Score System for transplant-age patients uses: hemoglobin <10 g/dl, leukocytes >25 × 109/L, platelets <100 × 109/L, circulating blasts ≥2%, constitutional symptoms, absence of CALR type 1 mutation, presence of high-molecular risk mutation (e.g., ASXL1, EZH2, SRSF2, IDH1/2), presence of two or more high-molecular risk mutations and a two-tiered revised cytogenetic risk stratification where very high risk and unfavorable karyotype are grouped together as “unfavorable” (reference in the text)