Patient characteristics at baseline according randomization
| . | Control induction treatment . | Clofarabine induction treatment . | No. of cases evaluated . |
|---|---|---|---|
| Total | 402 (100%) | 393 (100%) | |
| Sex, male | 215 (53%) | 229 (58%) | |
| Age, y | |||
| Median (range)* | 54 (18-65) | 56 (18-66) | |
| ≤45 | 108 (27%) | 112 (28%) | |
| 46-60 | 195 (49%) | 166 (42%) | |
| 61-65 | 99 (25%) | 115 (29%) | |
| Performance status | |||
| WHO 0 | 206 (51%) | 178 (45%) | |
| WHO 1 | 152 (38%) | 170 (43%) | |
| WHO 2 | 29 (7%) | 28 (7%) | |
| Unknown | 15 (4%) | 17 (4%) | |
| AML type | |||
| De novo | 346 (86%) | 341 (87%) | |
| sAML | 35 (9%) | 33 (8%) | |
| tAML | 21 (5%) | 19 (5%) | |
| High-risk RAEB | 42 (10%) | 38 (10%) | |
| First-degree relatives with AML | 9 (2%) | 7 (2%) | |
| Family history unknown | 51 (13%) | 49 (12%) | |
| WBC at diagnosis [×109/L] | |||
| ≤20 | 282 (70%) | 281 (72%) | |
| 20-100 | 94 (23%) | 87 (22%) | |
| >100 | 25 (6%) | 24 (6%) | |
| Median (range) | 6.4 (0.4-341) | 7.3 (0.2-229) | |
| Blasts (%) in bone marrow (median) | 51 | 51 | |
| Cytogenetics | |||
| t(8;21)* | 24 (6%) | 21 (5%) | |
| inv(16) | 14 (3%) | 15 (4%) | |
| CN X-Y | 208 (52%) | 184 (47%) | |
| CA rest | 94 (23%) | 105 (27%) | |
| Monosomal karyotype | 53 (13%) | 52 (13%) | |
| Unknown | 9 (2%) | 16 (4%) | |
| Gene mutations | |||
| NPM1 | 116 (31%) | 95 (25%) | 754 |
| FLT3-ITD | 68 (19%) | 71 (20%) | 704 |
| FLT3-TKD835 | 24 (7%) | 24 (7%) | 653 |
| NPM1 mut-FLT3-ITD neg | 69 (20%) | 50 (14%) | 696 |
| NPM1 mut-FLT3-ITD | 35 (10%) | 39 (11%) | |
| NPM1wt-FLT3-ITD neg | 209 (60%) | 229 (65%) | |
| NPM1wt-FLT3-ITD | 33 (10%) | 32 (9%) | |
| DNMT3A mutation | 82 (27%) | 85 (27%) | 609 |
| IDH1 mutation | 28 (9%) | 34 (11%) | 609 |
| IDH2 mutation | 34 (11%) | 36 (12%) | 609 |
| TET2 mutation | 34 (11%) | 41 (13%) | 609 |
| Bi-allelic CEBPA mutations | 12 (4%) | 14 (5%) | 573 |
| RUNX1 mutation | 40 (13%) | 40 (13%) | 609 |
| ASXL1 mutation | 31 (10%) | 32 (10%) | 609 |
| P53 mutation | 28 (9%) | 29 (9%) | 609 |
| SF3B1 mutation | 9 (3%) | 4 (1%) | 609 |
| SRSF2 mutation | 24 (8%) | 31 (10%) | 609 |
| PTPN11 mutation | 33 (11%) | 36 (12%) | 609 |
| KRAS mutation | 19 (6%) | 21 (7%) | 609 |
| NRAS mutation | 59 (20%) | 70 (23%) | 609 |
| MLL-PTD | 16 (7%) | 13 (5%) | 490 |
| JAK2 | 7 (2%) | 8 (3%) | 609 |
| EVI-1 overexpression | 36 (11%) | 46 (14%) | 641 |
| Prognostic risk according to ELN criteria 2010† | |||
| Favorable | 104 (26%) | 85 (22%) | |
| Intermediate I | 121 (30%) | 123 (31%) | |
| Intermediate II | 88 (22%) | 99 (25%) | |
| Adverse | 89 (22%) | 86 (22%) | |
| . | Control induction treatment . | Clofarabine induction treatment . | No. of cases evaluated . |
|---|---|---|---|
| Total | 402 (100%) | 393 (100%) | |
| Sex, male | 215 (53%) | 229 (58%) | |
| Age, y | |||
| Median (range)* | 54 (18-65) | 56 (18-66) | |
| ≤45 | 108 (27%) | 112 (28%) | |
| 46-60 | 195 (49%) | 166 (42%) | |
| 61-65 | 99 (25%) | 115 (29%) | |
| Performance status | |||
| WHO 0 | 206 (51%) | 178 (45%) | |
| WHO 1 | 152 (38%) | 170 (43%) | |
| WHO 2 | 29 (7%) | 28 (7%) | |
| Unknown | 15 (4%) | 17 (4%) | |
| AML type | |||
| De novo | 346 (86%) | 341 (87%) | |
| sAML | 35 (9%) | 33 (8%) | |
| tAML | 21 (5%) | 19 (5%) | |
| High-risk RAEB | 42 (10%) | 38 (10%) | |
| First-degree relatives with AML | 9 (2%) | 7 (2%) | |
| Family history unknown | 51 (13%) | 49 (12%) | |
| WBC at diagnosis [×109/L] | |||
| ≤20 | 282 (70%) | 281 (72%) | |
| 20-100 | 94 (23%) | 87 (22%) | |
| >100 | 25 (6%) | 24 (6%) | |
| Median (range) | 6.4 (0.4-341) | 7.3 (0.2-229) | |
| Blasts (%) in bone marrow (median) | 51 | 51 | |
| Cytogenetics | |||
| t(8;21)* | 24 (6%) | 21 (5%) | |
| inv(16) | 14 (3%) | 15 (4%) | |
| CN X-Y | 208 (52%) | 184 (47%) | |
| CA rest | 94 (23%) | 105 (27%) | |
| Monosomal karyotype | 53 (13%) | 52 (13%) | |
| Unknown | 9 (2%) | 16 (4%) | |
| Gene mutations | |||
| NPM1 | 116 (31%) | 95 (25%) | 754 |
| FLT3-ITD | 68 (19%) | 71 (20%) | 704 |
| FLT3-TKD835 | 24 (7%) | 24 (7%) | 653 |
| NPM1 mut-FLT3-ITD neg | 69 (20%) | 50 (14%) | 696 |
| NPM1 mut-FLT3-ITD | 35 (10%) | 39 (11%) | |
| NPM1wt-FLT3-ITD neg | 209 (60%) | 229 (65%) | |
| NPM1wt-FLT3-ITD | 33 (10%) | 32 (9%) | |
| DNMT3A mutation | 82 (27%) | 85 (27%) | 609 |
| IDH1 mutation | 28 (9%) | 34 (11%) | 609 |
| IDH2 mutation | 34 (11%) | 36 (12%) | 609 |
| TET2 mutation | 34 (11%) | 41 (13%) | 609 |
| Bi-allelic CEBPA mutations | 12 (4%) | 14 (5%) | 573 |
| RUNX1 mutation | 40 (13%) | 40 (13%) | 609 |
| ASXL1 mutation | 31 (10%) | 32 (10%) | 609 |
| P53 mutation | 28 (9%) | 29 (9%) | 609 |
| SF3B1 mutation | 9 (3%) | 4 (1%) | 609 |
| SRSF2 mutation | 24 (8%) | 31 (10%) | 609 |
| PTPN11 mutation | 33 (11%) | 36 (12%) | 609 |
| KRAS mutation | 19 (6%) | 21 (7%) | 609 |
| NRAS mutation | 59 (20%) | 70 (23%) | 609 |
| MLL-PTD | 16 (7%) | 13 (5%) | 490 |
| JAK2 | 7 (2%) | 8 (3%) | 609 |
| EVI-1 overexpression | 36 (11%) | 46 (14%) | 641 |
| Prognostic risk according to ELN criteria 2010† | |||
| Favorable | 104 (26%) | 85 (22%) | |
| Intermediate I | 121 (30%) | 123 (31%) | |
| Intermediate II | 88 (22%) | 99 (25%) | |
| Adverse | 89 (22%) | 86 (22%) | |
N refers to number of patients. Gene mutations are as follows: NPM1 nuclephosmin-1; FLT3, fms-like tyrosine kinase-3; FLT3-TKD835, FLT3 gene with point mutation at position D835; DNMT3A, DNA methyltransferase 3A; IDH1/IDH2, isocitrate dehydrogenase 1 and 2; TET2, Ten-Eleven translocation-2; CEPBA, CCAAT/enhancer-binding protein α; RUNX1, runt-related transcription factor 1; ASXL1, additional sex combs like 1; p53; SF3B1, splicing factor 3B subunit; SRSF2, serine and arginine rich splicing factor 2; PTPN11, protein tyrosine phosphatase, nonreceptor type 11; MLL, myeloid/lymphoid or mixed-lineage leukemia; JAK2, Janus kinase 2. RAEB with an international prognostic score of ≥1.5 IPSS is as described previously.6 The ELN prognostic risk categories are as described by Döhner et al.12
CA, abnormal cytogenetics; CN, normal cytogenetics; EVI1, ecotropic virus integration 1 gene; FLT3-ITD negative, FLT3 without internal tandem duplications; ITD, internal tandem duplication; mut, mutation; neg, negative; PTD, partial tandem duplication; sAML, secondary AML (after myelodysplastic syndrome and antecedent hematological disease); tAML, therapy-related AML (in case of prior chemotherapy or radiotherapy. For details, see the Methods section); WBC, white blood cell count at diagnosis; WHO, World Health Organization.
AML with core-binding factor abnormalities: t(8;21) (q22;q22), inv(16)(p13.1;q22), or t(16;16)(p13.1;q22) Monosomal karyotype is defined as described by Breems et al.13
According to Döhner et al12 but slightly modified for bi-allelic CEBPA gene mutations, as detailed in the supplemental Appendix.