Table 2.
Clinical, laboratory, genetic, and outcome characteristics of 121 advanced systemic mastocytosis (AdvSM) patients stratified by an expressed allele burden/variant allele frequency ratio of ≤2 (cohort A) and > 2 (cohort B).
| Variables |
KIT D816V EAB/VAF Ratio ≤ 2 (Cohort A) |
KIT D816V EAB/VAF Ratio > 2 (Cohort B) |
p-Value |
|---|---|---|---|
| Number of patients (n) | 77 | 44 | - |
| Age in years, median (range) | 71 (30–90) | 77 (52–88) | - |
| Male, n (%) | 49 (63) | 32 (73) | - |
| Diagnosis | |||
| ASM, n (%) | 14 (18) | 4 (11) | - |
| MCL, n (%) | 2 (3) | - | - |
| SM/MCL-AHN, n (%) | 61 (79) | 40 (90) | - |
| AHN-subtypes | |||
| MDS/MPN-u, n (%) | 18 (30) | 13 (33) | - |
| CMML, n (%) | 27 (44) | 17 (43) | - |
| MDS, n (%) | 5 (8) | 6 (15) | - |
| MPN-eo, n (%) | 1 (2) | - | |
| AML, n (%) | 1 (2) | 1 (2) | - |
| CEL, n (%) | 7 (11) | 1 (2) | - |
| PMF, n (%) | 2 (3) | 2 (5) | - |
| Progression to | |||
| AML, n (%) | 8 (10) | 3 (7) | - |
| MCL, n (%) | 6 (8) | 2 (5) | - |
| C-findings | |||
| Hemoglobin, g/dL; median (range) | 11.4 (5.8–15.8) | 9.8 (7.5–14.5) | 0.006 |
| <10 g/dL; n (%) | 20 (29) | 21 (53) | 0.01 |
| Platelets, ×109/L; median (range) | 133 (12–618) | 106 (28–958) | n.s. |
| <100 × 109/L, n (%) | 31 (44) | 19 (48) | n.s. |
| Alkaline phosphatase, U/L; median (range) | 188 (33–1206) | 303 (53–1279) | n.s. |
| >150 U/L, n (%) | 39 (57) | 31 (79) | 0.01 |
| Albumin, g/L; median (range) | 38 (16–48) | 36 (22–48) | n.s. |
| <34 g/L, n (%) | 23 (34) | 14 (40) | n.s. |
| Ascites, n (%) | 39 (53) | 25 (61) | n.s. |
| B-findings | |||
| MC-infiltration in BM histology, %; median (range) | 35 (3–95) | 30 (0–100) | n.s. |
| Serum tryptase, µg/L; median (range) | 170 (11–1382) | 211 (18–875) | n.s. |
| >100 µg/L, n (%) | 51 (73) | 28 (74) | n.s. |
| Splenomegaly, n (%) | 60 (87) | 37 (90) | n.s. |
| Hepatomegaly, n (%) | 33 (52) | 28 (72) | 0.05 |
| Additional SM and/or AHN relevant findings | |||
| Leukocytes, ×109/L; median (range) | 10.6 (5.8–79.3) | 7.6 (1.0–89.4) | n.s. |
| Monocytes, %; median (range) | 7 (1–46) | 11 (1–31) | 0.01 |
| Eosinophils, %, median (range) | 3 (0–81) | 6 (0–66) | n.s. |
| Vitamin B12, ng/L; median (range) | 1188 (114–6000) | 2842 (489–6000) | 0.02 |
| >180 ng/L, n (%) | 50 (96) | 32 (100) | n.s. |
| KIT D816V EAB in PB, %, median (range) | 30 (0–95) | 28 (2–88) | n.s. |
| KIT D816V VAF in PB, %, median (range) | 27.0 (0.0–49.8) | 4.0 (0.1–30.8) | <0.001 |
| GI-infiltration, n (%) | 30 (41) | 19 (43) | n.s. |
| S/A/R mutation(s) a, n (%) | 38 (51) | 31 (74) | 0.02 |
| Treatment | |||
| Midostaurin b, n (%) | 26 (48) | 14 (39) | n.s. |
| Cladribine b, n (%) | 6 (11) | 7 (19) | n.s. |
| Midostaurin + cladribine b, n (%) | 22 (41) | 15 (36) | n.s. |
| Response to any treatment c, n (%) | 10 (30) | 9 (45) | n.s. |
| Outcome | |||
| Follow-up, years, median (range) | 3.5 (0.0–24.6) | 2.2 (0.0–11.9) | - |
| Death, n (%) | 33 (43) | 27 (61) | - |
AHN, associated hematological neoplasm; AML, acute myeloid leukemia; ASM, aggressive systemic mastocytosis; BM, bone marrow; CEL, chronic eosinophilic leukemia; CMML, chronic myelomonocytic leukemia; EAB, expressed allele burden; GI, gastrointestinal; MCL, mast cell leukemia; MDS, myelodysplastic syndromes; MPN, myeloproliferative neoplasms; -u, unclassified; -eo, eosinophila; n, number; PB, peripheral blood; PMF, primary myelofibrosis; S/A/R, at least one mutation in the SRSF2, ASXL1, RUNX1 gene panel; SM, systemic mastocytosis; VAF, variant allele frequency; a data available for n = 75 patients (cohort A) and n = 42 patients (cohort B); b data available for n = 54 (70%) patients (cohort A) and n = 36 (82%) patients (cohort B); c, data available for n = 34 patients (cohort A) and n = 20 patients (cohort B).