Table 1. Clinical and laboratory features and subsequent events in 261 patients with World Health Organization defined chronic myelomonocytic leukemia (CMML), stratified by the presence or absence of TET2 mutations.
| Variable | All patients with CMML (n=261) | CMML patients with TET2 mutations (n=109) | CMML patients without TET2 mutations (n=152) | P-value |
|---|---|---|---|---|
| Age in years; median (range) | 70 (20–91) | 64.5 (20–87) | 70 (27–91) | 0.067 |
| Males; n (%) | 168 (64) | 9 (56) | 159 (65) | 0.48 |
| Hemoglobin g/dl; median (range) | 10.6 (6.4–16.9) | 9.6 (6.8–13.2) | 10.7 (6.4–16.9) | 0.093 |
| MCV femtoliter; median (range) | 91 (59–119) | 91 (75–112) | 91 (59–119) | 0.5 |
| WBC × 109/l; median (range) | 12.1 (1.5–264) | 12.6 (2.9–71.5) | 12 (1.5–264) | 0.83 |
| ANC × 109/l; median (range) | 5.8 (0–151) | 6.7 (1–39.2) | 5.7 (0–151) | 0.74 |
| AMC × 109/l; median (range) | 2.3 (1.0–40) | 1.7 (1.0–20) | 2.4 (1.0–40) | 0.756 |
| ALC × 109/l; median (range) | 1.7 (0–22) | 1.9 (0.4–5.6) | 1.7 (0–22) | 0.82 |
| Platelets × 109 /l; median (range) | 97 (10–840) | 112 (11–840) | 96 (10–726) | 0.45 |
| Presence of circulating immature myeloid cells; n (%) | 142 (54) | 9 (60) | 133 (55) | 0.7 |
| PB blast % median (range) | 0 (0–19) | 0 (0–19) | 0 (0–7) | 0.3 |
| BM blast % ; median (range) | 3 (0–19) | 3 (0–13) | 3 (0–19) | 0.9 |
| BM cellularity % | 80 (40–100) | |||
| Lactate dehydrogenase levels IU/ml; n (range) | 225 (84–1296) | 223 (109–294) | 225 (84–1296) | 0.48 |
| Next-generation sequencing analysis; n (%) | ||||
| Epigenetic regulators | ||||
| DNMT3A | (45) | (50) | (45) | 0.7 |
| IDH1 | 4 (2) | 0 (0) | 4 (2) | 0.6 |
| IDH2 | 11 (4) | 0 (0) | 11 (4) | 0.38 |
| Chromatin regulation | ||||
| ASXL1 | 120 (50) | 6 (37) | 114 (51) | 0.3 |
| EZH2 | 3 (1) | 0 (0) | 3 (1) | 0.656 |
| SUZ12 | 0 | 0 (0) | 0 (0) | − |
| Transcription factors | ||||
| RUNX1 | 16 (6) | 2 (12) | 14 (6) | 0.27 |
| Spliceosome components | ||||
| SF3B1 | 13 (5) | 4 (25) | 9 (4) | 0.0001 |
| SRSF2 | 105 (40) | 1 (6) | 104 (42) | 0.0042 |
| U2AF1 | 16 (6) | 2 (12) | 14 (6) | 0.2 |
| ZRSR2 | 5 (3) | 0 (0) | 5 (2) | 0.8 |
| Cell signalling | ||||
| JAK2 V617F | 17 (7) | 1 (6) | 16 (7) | 0.9 |
| CALR | 1 (0.5) | 0 (0) | 1 (0.5) | 0.8 |
| MPL | 1 (0.4) | 0 (0) | 1 (0.5) | 0.8 |
| SH2B3 | 1 (0.5) | 0 (0) | 1 (0.5) | 0.8 |
| CBL | 25 (10) | 0 (0) | 25 (10) | 0.4 |
| KRAS | 8 (3) | 0 (0) | 8 (3) | 0.5 |
| NRAS | 37 (14) | 2 (16) | 35 (14) | 0.8 |
| PTPN11 | 6 (2) | 2 (12) | 4 (2) | 0.005 |
| CSF3R | 3 (1) | 0 (0) | 3 (1) | 0.7 |
| C-KIT | 7 (3) | 1 (6) | 6 (2) | 0.4 |
| FLT3TKD | 1 (0.5) | 0 (0) | 1 (0.5) | 0.8 |
| NPM1 | 0 | 0 (0) | 0 (0) | − |
| Tumor suppressor genes | ||||
| Tp53 | 10 (4) | 2 (12) | 9 (4) | 0.09 |
| PHF6 | 0 | 0 (0) | 0 (0) | − |
| Others | ||||
| SETBP1 | 34 (13) | 2 (12) | 32 (13) | 0.9 |
| IKZF | 0 | 0 (0) | 0 (0) | − |
| 2008 WHO morphological subtypes; n (%) | ||||
| CMML-1 | 221 (84) | 13 (81) | 208 (85) | 0.7 |
| CMML-2 | 40 (16) | 3 (19) | 37 (15) | |
| 2016 WHO morphological subtypes; n (%) | ||||
| CMML-0 | 154 (59) | 10 (62) | 144 (59) | 0.9 |
| CMML-1 | 65 (25) | 4 (25) | 61 (25) | |
| CMML-2 | 42 (16) | 2 (12) | 40 (16) | |
| aSpanish Cytogenetic risk stratification; n (%) | ||||
| Low | 180 (72) | 11 (69) | 169 (72) | 0.1 |
| Intermediate | 43 (17) | 1 (6) | 42 (18) | |
| High | 27 (11) | 4 (25) | 23 (10) | |
| aMayo-French cytogenetic risk stratification; n (%) | ||||
| Low | 180 (72) | 11 (69) | 169 (72) | 0.4 |
| Intermediate | 57 (23) | 3 (19) | 54 (23) | |
| High | 13 (5) | 2 (12) | 11 (5) | |
| Mayo prognostic model; n (%) | ||||
| Low | 89 (34) | 3 (20) | 86 (35) | 0.2 |
| Intermediate | 83 (32) | 4 (27) | 79 (32) | |
| High | 87 (34) | 8 (53) | 79 (32) | |
| Molecular Mayo model; n (%) | ||||
| Low | 26 (10) | 0 (0) | 26 (11) | 0.5 |
| Intermediate-1 | 72 (28) | 4 (25) | 68 (28) | |
| Intermediate-2 | 79 (30) | 6 (37) | 73 (30) | |
| High | 81 (31) | 6 (37) | 75 (31) | |
| GFM CMML prognostic model; n (%) | ||||
| Low | 119 (46) | 9 (56) | 110 (45) | 0.4 |
| Intermediate | 92 (36) | 6 (37) | 86 (35) | |
| High | 48 (18) | 1 (6) | 47 (19) | |
| Leukemic transformations; n (%) | 37 (14) | 4 (25) | 33 (13) | 0.2 |
| Deaths; n (%) | 174 (67) | 10 (62) | 164 (67) | 0.7 |
Abbreviations: ALC, absolute lymphocyte count; AMC, absolute monocyte count; ANC, absolute neutrophil count; BM, bone marrow; CMML, chronic myelomonocytic leukemia; FAB, French American British; GFM, Groupe Français des Myélodysplasies; MCV, mean corpuscular volume; PB, peripheral blood; WBC, white blood cell count; WHO, World Health Organization.
a
Cytogenetic studies were available for 250 patients with chronic myelomonocytic leukemia at diagnosis.