Baseline characteristics of MPN-AP/BP cohort at time of transformation
| Variable (%) . | Whole cohort (N = 138) . | Intensive (AML-type induction) (N = 81) . | Nonintensive (HMA or AzaVen) (N = 57) . | P value (intensive vs nonintensive) . |
|---|---|---|---|---|
| Age at transformation, median [range], y | 64 [22-87] | 60 [22-76] | 70 [42-87] | <.001 |
| Sex | .16 | |||
| Male | 87 (63) | 47 (58) | 40 (70) | |
| Female | 51 (37) | 34 (42) | 17 (30) | |
| Transformation type | <.001 | |||
| AP | 34 (25) | 9 (11) | 25 (44) | |
| BP | 104 (75) | 72 (89) | 32 (56) | |
| Chronic MPN diagnosis∗ | .16 | |||
| PV/ET | 35 (25) | 23 (28) | 12 (21) | |
| MPN-U | 15 (11) | 12 (15) | 3 (5) | |
| PMF | 36 (26) | 20 (25) | 16 (28) | |
| PPV/PET-MF | 52 (38) | 26 (32) | 26 (46) | |
| Number of prior MPN treatments in chronic phase | N = 137 | N = 80 | N = 57 | .16 |
| 0-1 | 80 (58) | 51 (64) | 29 (51) | |
| ≥2 | 57 (42) | 29 (36) | 28 (49) | |
| ECOG | N = 126 | N = 74 | N = 52 | .03 |
| 0-1 | 106 (84) | 67 (91) | 39 (75) | |
| ≥2 | 20 (16) | 7 (9) | 13 (25) | |
| Palpable spleen length (BCM) at time of AP/BP | N = 126 | N = 71 | N = 55 | .80 |
| Not palpable | 47 (37) | 24 (34) | 23 (42) | |
| < 10 cm | 30 (24) | 17 (24) | 13 (24) | |
| ≥10 cm | 38 (30) | 23 (32) | 15 (27) | |
| Splenectomy | 11 (9) | 7 (10) | 4 (7) | |
| Laboratory parameters† , median (range) [number] | ||||
| Hb, g/L | 87 (51-177) [n = 132] | 87 (51-177) [n = 77] | 87 (51-134) [55] | .58 |
| WBC, ×109/L | 12.2 (1-213) [n = 134] | 12.8 (1.1-213) [n = 79] | 11.5 (1-126) [n = 55] | .56 |
| ANC, ×109/L | 3.8 (0-91) [n = 123] | 3.8 (0-91) [n = 70] | 3.6 (0.2-79) [n = 53] | .77 |
| Platelets, ×109/L | 90 (6-1918) [n = 133] | 73 (6-865) [n = 78] | 109 (13-1918) [n = 55] | .01 |
| PB blasts, % | 16 (0-83) [n = 134] | 19.5 (0-83) [n = 78] | 12 (0-83) [n = 56] | .03 |
| BM blasts, % | 25 (3-90) [n = 113] | 31 (4-90) [n = 67] | 20 (3-89) [n = 46] | .03 |
| LDH, U/L | 598 (43-5893) [n = 127] | 681 (144-5893) [n = 74] | 553 (43-4000) [n = 53] | .15 |
| Albumin, g/L | 39 (27-47) [n = 124] | 38 (27-47) [n = 74] | 42 (30-45) [n = 50] | .03 |
| ELN 2022 RISK | N = 121 | N = 69 | N = 52 | .14 |
| Adverse | 72 (60) | 37 (54) | 35 (67) | |
| Nonadverse | 49 (40) | 32 (46) | 17 (33) | |
| MPN driver mutations | N = 101 | N = 53 | N = 48 | .29 |
| JAK2/MPL | 66 (65) | 31 (58) | 35 (73) | |
| CALR | 12 (12) | 7 (13) | 5 (10) | |
| Triple negative | 23 (23) | 15 (29) | 8 (17) | |
| Genes mutated in ≥5% of patients | N = 101 | N = 53 | N = 48 | |
| ASXL1 | 29 (29) | 10 (19) | 19 (40) | .03 |
| TET2 | 26 (26) | 18 (34) | 8 (17) | .07 |
| SRSF2 | 26 (26) | 10 (19) | 16 (33) | .11 |
| IDH1/2 | 22 (22) | 11 (21) | 11 (23) | .81 |
| TP53 | 21 (21) | 13 (25) | 8 (17) | .46 |
| RUNX1 | 19 (19) | 8 (15) | 11 (23) | .45 |
| DNMT3A | 16 (16) | 7 (13) | 9 (19) | .59 |
| NRAS | 13 (13) | 5 (9) | 8 (17) | .38 |
| EZH2 | 10 (10) | 4 (8) | 6 (12) | .51 |
| STAG2 | 12 (12) | 5 (9) | 7 (15) | .54 |
| PTPN11 | 7(7) | 1 (2) | 6 (12) | .05 |
| CEBPA | 6 (6) | 4 (8) | 2 (4) | .68 |
| SETBP1 | 6 (6) | 4 (8) | 2 (4) | .68 |
| U2AF1 | 6 (6) | 0 | 6 (12) | .01 |
| CBL | 5 (5) | 1 (2) | 4 (8) | .19 |
| SF3B1 | 6 (6) | 4 (8) | 2 (4) | .68 |
| ZRSR2 | 5 (5) | 2 (4) | 3 (6) | .67 |
| Mutations by pathway | N = 101 | N = 53 | N = 48 | |
| JAK-STAT pathway‡ | 80 (79) | 38 (72) | 42 (88) | .08 |
| RAS pathway§ | 23 (23) | 10 (19) | 13 (27) | .4 |
| RNA splicing‖ | 40 (40) | 15 (28) | 25 (52) | .02 |
| Epigenetic regulation¶ | 67 (66) | 35 (66) | 32 (67) | 1.0 |
| Transcription factors# | 32 (32) | 15 (28) | 17 (35) | .5 |
| Number of mutations | N = 101 | N = 53 | N = 48 | .04 |
| 0-1 | 17 (17) | 12 (23) | 5 (10) | |
| 2-3 | 36 (36) | 22 (42) | 14 (29) | |
| ≥4 | 48 (48) | 19 (36) | 29 (60) |
| Variable (%) . | Whole cohort (N = 138) . | Intensive (AML-type induction) (N = 81) . | Nonintensive (HMA or AzaVen) (N = 57) . | P value (intensive vs nonintensive) . |
|---|---|---|---|---|
| Age at transformation, median [range], y | 64 [22-87] | 60 [22-76] | 70 [42-87] | <.001 |
| Sex | .16 | |||
| Male | 87 (63) | 47 (58) | 40 (70) | |
| Female | 51 (37) | 34 (42) | 17 (30) | |
| Transformation type | <.001 | |||
| AP | 34 (25) | 9 (11) | 25 (44) | |
| BP | 104 (75) | 72 (89) | 32 (56) | |
| Chronic MPN diagnosis∗ | .16 | |||
| PV/ET | 35 (25) | 23 (28) | 12 (21) | |
| MPN-U | 15 (11) | 12 (15) | 3 (5) | |
| PMF | 36 (26) | 20 (25) | 16 (28) | |
| PPV/PET-MF | 52 (38) | 26 (32) | 26 (46) | |
| Number of prior MPN treatments in chronic phase | N = 137 | N = 80 | N = 57 | .16 |
| 0-1 | 80 (58) | 51 (64) | 29 (51) | |
| ≥2 | 57 (42) | 29 (36) | 28 (49) | |
| ECOG | N = 126 | N = 74 | N = 52 | .03 |
| 0-1 | 106 (84) | 67 (91) | 39 (75) | |
| ≥2 | 20 (16) | 7 (9) | 13 (25) | |
| Palpable spleen length (BCM) at time of AP/BP | N = 126 | N = 71 | N = 55 | .80 |
| Not palpable | 47 (37) | 24 (34) | 23 (42) | |
| < 10 cm | 30 (24) | 17 (24) | 13 (24) | |
| ≥10 cm | 38 (30) | 23 (32) | 15 (27) | |
| Splenectomy | 11 (9) | 7 (10) | 4 (7) | |
| Laboratory parameters† , median (range) [number] | ||||
| Hb, g/L | 87 (51-177) [n = 132] | 87 (51-177) [n = 77] | 87 (51-134) [55] | .58 |
| WBC, ×109/L | 12.2 (1-213) [n = 134] | 12.8 (1.1-213) [n = 79] | 11.5 (1-126) [n = 55] | .56 |
| ANC, ×109/L | 3.8 (0-91) [n = 123] | 3.8 (0-91) [n = 70] | 3.6 (0.2-79) [n = 53] | .77 |
| Platelets, ×109/L | 90 (6-1918) [n = 133] | 73 (6-865) [n = 78] | 109 (13-1918) [n = 55] | .01 |
| PB blasts, % | 16 (0-83) [n = 134] | 19.5 (0-83) [n = 78] | 12 (0-83) [n = 56] | .03 |
| BM blasts, % | 25 (3-90) [n = 113] | 31 (4-90) [n = 67] | 20 (3-89) [n = 46] | .03 |
| LDH, U/L | 598 (43-5893) [n = 127] | 681 (144-5893) [n = 74] | 553 (43-4000) [n = 53] | .15 |
| Albumin, g/L | 39 (27-47) [n = 124] | 38 (27-47) [n = 74] | 42 (30-45) [n = 50] | .03 |
| ELN 2022 RISK | N = 121 | N = 69 | N = 52 | .14 |
| Adverse | 72 (60) | 37 (54) | 35 (67) | |
| Nonadverse | 49 (40) | 32 (46) | 17 (33) | |
| MPN driver mutations | N = 101 | N = 53 | N = 48 | .29 |
| JAK2/MPL | 66 (65) | 31 (58) | 35 (73) | |
| CALR | 12 (12) | 7 (13) | 5 (10) | |
| Triple negative | 23 (23) | 15 (29) | 8 (17) | |
| Genes mutated in ≥5% of patients | N = 101 | N = 53 | N = 48 | |
| ASXL1 | 29 (29) | 10 (19) | 19 (40) | .03 |
| TET2 | 26 (26) | 18 (34) | 8 (17) | .07 |
| SRSF2 | 26 (26) | 10 (19) | 16 (33) | .11 |
| IDH1/2 | 22 (22) | 11 (21) | 11 (23) | .81 |
| TP53 | 21 (21) | 13 (25) | 8 (17) | .46 |
| RUNX1 | 19 (19) | 8 (15) | 11 (23) | .45 |
| DNMT3A | 16 (16) | 7 (13) | 9 (19) | .59 |
| NRAS | 13 (13) | 5 (9) | 8 (17) | .38 |
| EZH2 | 10 (10) | 4 (8) | 6 (12) | .51 |
| STAG2 | 12 (12) | 5 (9) | 7 (15) | .54 |
| PTPN11 | 7(7) | 1 (2) | 6 (12) | .05 |
| CEBPA | 6 (6) | 4 (8) | 2 (4) | .68 |
| SETBP1 | 6 (6) | 4 (8) | 2 (4) | .68 |
| U2AF1 | 6 (6) | 0 | 6 (12) | .01 |
| CBL | 5 (5) | 1 (2) | 4 (8) | .19 |
| SF3B1 | 6 (6) | 4 (8) | 2 (4) | .68 |
| ZRSR2 | 5 (5) | 2 (4) | 3 (6) | .67 |
| Mutations by pathway | N = 101 | N = 53 | N = 48 | |
| JAK-STAT pathway‡ | 80 (79) | 38 (72) | 42 (88) | .08 |
| RAS pathway§ | 23 (23) | 10 (19) | 13 (27) | .4 |
| RNA splicing‖ | 40 (40) | 15 (28) | 25 (52) | .02 |
| Epigenetic regulation¶ | 67 (66) | 35 (66) | 32 (67) | 1.0 |
| Transcription factors# | 32 (32) | 15 (28) | 17 (35) | .5 |
| Number of mutations | N = 101 | N = 53 | N = 48 | .04 |
| 0-1 | 17 (17) | 12 (23) | 5 (10) | |
| 2-3 | 36 (36) | 22 (42) | 14 (29) | |
| ≥4 | 48 (48) | 19 (36) | 29 (60) |
BCM, below costal margin; LDH, lactate dehydrogenase; MPN-U, MPN unclassifiable; PET-MF, post–ET MF; PMF, primary MF; PPV-MF, post–PV MF. Bold values are statistically significant.
Before leukemic transformation.
One patient received decitabine and the remainder received azacitidine.
JAK2, MPL, CALR, CSF3R.
CBL, NRAS, PTPN11, KIT, KRAS.
SF3B1, SRSF2, U2AF1, ZRSR2.
ASXL1, BCOR, DNMT3A, EZH2, IDH1/2, SETBP1, TET2.
CEBPA, CUX1, ETV6, GATA2, IKZF1, PHF6, RUNX1, WT1.