Baseline and follow-up clinical and hematologic characteristics of the whole cohort of 281 patients with CALRm ET and after stratification in CALR-high and CALR-low, based on the ≥60% threshold level of VAF, as determined by ROC analysis using MFS as the main end point
| Variables . | CALRm (n = 281) . | CALR-high (n = 21) . | CALR-low (n = 260) . | P (high vs low) . |
|---|---|---|---|---|
| Age at diagnosis∗, y (range) | 53.6 (18-86) | 52.4 (27-79) | 53.7 (18-86) | .80 |
| Male sex (%) | 145 (51.6) | 11 (52.4) | 134 (51.5) | .94 |
| CALRm type | .008 | |||
| Type 1/like | 152 (54.0) | 11 (52.4) | 141 (54.2) | |
| Type 2/like | 101 (36.0) | 4 (19.0) | 97 (37.3) | |
| Indeterminate | 28 (10.0) | 6 (28.6) | 22 (8.5) | |
| CALRm VAF % (mean ± SD) | 40.9 (+15.4) | 72.2 (9.1) | 38.5 (+12.9) | .001 |
| Presence of at least an additional myeloid variant (n = 99) | 34 (34.7) | 8 (66.7) | 26 (30.2) | .013 |
| History of thrombosis† | 17 (6.0) | 3 (14.3) | 14 (5.4) | .10 |
| History of bleeding† (n = 205) | 4 (2.0) | 1 (5.6) | 3 (1.6) | .25 |
| Leukocytes (×109/L)∗ | 7.8 (2.4-17.3) | 9.0 (4.4-17.3) | 7.8 (2.4-13.2) | .17 |
| Hemoglobin (g/dL)∗ | 13.5 (8.4-16.4)‡ | 12.8 (8.4-14.0)‡ | 13.6 (10.1-16.4) | .019 |
| Hematocrit (%)∗ | 41.4 (26-4-49.2) | 37.4 (26.5-46.7) | 41.6 (29.6-49.2) | .012 |
| Platelets (×1012/L)∗ | 817 (460-2851) | 789 (527-1729) | 817 (460-2815) | .93 |
| BM fibrosis grade 1† | 39 (13.9) | 3 (14.3) | 36 (13.8) | .81 |
| Constitutional symptoms† | 15 (5.3) | 1 (4.8) | 14 (5.0) | .77 |
| Microvascular symptoms† | 79 (28.1) | 8 (38.0) | 71 (27.3) | .38 |
| Splenomegaly† | 23 (8.2) | 3 (14.3) | 20 (7.8) | .19 |
| IPSET-rev thrombosis, n (%) | ||||
| Very low | 113 (40.2) | 7 (33.3) | 106 (40.8) | |
| Low | 8 (2.8) | 1 (4.8) | 7 (2.7) | .53 |
| Intermediate | 140 (49.8) | 10 (47.6) | 130 (50) | |
| High | 20 (7.2) | 3 (14.3) | 17 (6.5) | |
| IPSET survival (n = 245), n (%) | ||||
| Low | 135 (55.1) | 7 (50.0) | 128 (55.4) | |
| Intermediate | 94 (38.4) | 4 (28.6) | 90 (39.0) | .07 |
| High | 16 (6.5) | 3 (21.4) | 13 (5.6) | |
| Events during follow-up | ||||
| Anemia in FU† (n = 193) | 41 (21.8) | 9 (69.2) | 33 (18.3) | <.001 |
| Leukoerythroblastosis in FU† (n = 180) | 19 (10.6) | 6 (46.2) | 13 (7.8) | <.001 |
| Splenomegaly in FU† (n = 184) | 26 (14.1) | 5 (50.0) | 21 (12.1) | <.001 |
| Symptoms in FU† (n = 195) | 14 (7.2) | 1 (9.1) | 13 (7.1) | .80 |
| Thrombosis in FU | 28 (10.0) | 1 (4.8) | 27 (10.4) | .41 |
| Bleeding episodes in FU† | 13 (6.4) | 2 (15.4) | 11 (5.8) | .17 |
| Progression to PET MF† | 50 (17.8) | 11 (52.4) | 39 (15.0) | <.001 |
| BP† | 2 (0.7) | 0 (0.0) | 2 (0.8) | .69 |
| Variables . | CALRm (n = 281) . | CALR-high (n = 21) . | CALR-low (n = 260) . | P (high vs low) . |
|---|---|---|---|---|
| Age at diagnosis∗, y (range) | 53.6 (18-86) | 52.4 (27-79) | 53.7 (18-86) | .80 |
| Male sex (%) | 145 (51.6) | 11 (52.4) | 134 (51.5) | .94 |
| CALRm type | .008 | |||
| Type 1/like | 152 (54.0) | 11 (52.4) | 141 (54.2) | |
| Type 2/like | 101 (36.0) | 4 (19.0) | 97 (37.3) | |
| Indeterminate | 28 (10.0) | 6 (28.6) | 22 (8.5) | |
| CALRm VAF % (mean ± SD) | 40.9 (+15.4) | 72.2 (9.1) | 38.5 (+12.9) | .001 |
| Presence of at least an additional myeloid variant (n = 99) | 34 (34.7) | 8 (66.7) | 26 (30.2) | .013 |
| History of thrombosis† | 17 (6.0) | 3 (14.3) | 14 (5.4) | .10 |
| History of bleeding† (n = 205) | 4 (2.0) | 1 (5.6) | 3 (1.6) | .25 |
| Leukocytes (×109/L)∗ | 7.8 (2.4-17.3) | 9.0 (4.4-17.3) | 7.8 (2.4-13.2) | .17 |
| Hemoglobin (g/dL)∗ | 13.5 (8.4-16.4)‡ | 12.8 (8.4-14.0)‡ | 13.6 (10.1-16.4) | .019 |
| Hematocrit (%)∗ | 41.4 (26-4-49.2) | 37.4 (26.5-46.7) | 41.6 (29.6-49.2) | .012 |
| Platelets (×1012/L)∗ | 817 (460-2851) | 789 (527-1729) | 817 (460-2815) | .93 |
| BM fibrosis grade 1† | 39 (13.9) | 3 (14.3) | 36 (13.8) | .81 |
| Constitutional symptoms† | 15 (5.3) | 1 (4.8) | 14 (5.0) | .77 |
| Microvascular symptoms† | 79 (28.1) | 8 (38.0) | 71 (27.3) | .38 |
| Splenomegaly† | 23 (8.2) | 3 (14.3) | 20 (7.8) | .19 |
| IPSET-rev thrombosis, n (%) | ||||
| Very low | 113 (40.2) | 7 (33.3) | 106 (40.8) | |
| Low | 8 (2.8) | 1 (4.8) | 7 (2.7) | .53 |
| Intermediate | 140 (49.8) | 10 (47.6) | 130 (50) | |
| High | 20 (7.2) | 3 (14.3) | 17 (6.5) | |
| IPSET survival (n = 245), n (%) | ||||
| Low | 135 (55.1) | 7 (50.0) | 128 (55.4) | |
| Intermediate | 94 (38.4) | 4 (28.6) | 90 (39.0) | .07 |
| High | 16 (6.5) | 3 (21.4) | 13 (5.6) | |
| Events during follow-up | ||||
| Anemia in FU† (n = 193) | 41 (21.8) | 9 (69.2) | 33 (18.3) | <.001 |
| Leukoerythroblastosis in FU† (n = 180) | 19 (10.6) | 6 (46.2) | 13 (7.8) | <.001 |
| Splenomegaly in FU† (n = 184) | 26 (14.1) | 5 (50.0) | 21 (12.1) | <.001 |
| Symptoms in FU† (n = 195) | 14 (7.2) | 1 (9.1) | 13 (7.1) | .80 |
| Thrombosis in FU | 28 (10.0) | 1 (4.8) | 27 (10.4) | .41 |
| Bleeding episodes in FU† | 13 (6.4) | 2 (15.4) | 11 (5.8) | .17 |
| Progression to PET MF† | 50 (17.8) | 11 (52.4) | 39 (15.0) | <.001 |
| BP† | 2 (0.7) | 0 (0.0) | 2 (0.8) | .69 |
Anemia in FU, development of stable hemoglobin <10 g/dL in the absence of bleeding or any other identifiable causes of anemia; BM, bone marrow; Dx, diagnosis; FU, follow-up; Leukocytosis in FU, appearance of stable count >15 109/L leukocytes in the absence of any other identifiable causes of leukocytosis; Thrombocytopenia in FU, development of stable <100 × 1012/L platelets in the absence of any other identifiable causes of thrombocytopenia; Leukoerythroblastosis in FU, appearance of a diagnostic leucoerythroblastic picture; SD, standard deviation; Splenomegaly in FU means, appearance of a palpable spleen of >5 cm from left costal margin in patients without splenomegaly at dx, or a >50% increase in palpable spleen from dx; Symptoms in FU, appearance of constitutional symptoms (weight loss, night sweats, not-infectious fever) in patients without symptoms at dx. Values in bold indicate statistical significance.
Median (range).
n (%).
One patient in CALR-1 and 2 patients in CALR-2 presented hemoglobin level <10 g/dL owing to known thalassemic trait; after exclusion of these patients, the median hemoglobin level in the population resulted was 13.5 g/dL (10.5-16.4).