Page 232 - Haematologica Vol. 110 - January 2025

LETTER TO THE EDITOR
Variable
CD2 expression
Overall N=1111
Negative N=531
Positive N=581
P
Neutrophils, x109/L
4.2 (2.0-7.2)
5.7 (2.2-8.7)
4.0 (1.9-6.2)
0.22
Eosinophils, x109/L
0.35 (0.06-1.29)
0.33 (0.07-1.01)
0.37 (0.06-1.84)
0.52
Monocytes, x109/L
1.00 (0.46-1.81)
1.00 (0.37-1.89)
0.83 (0.50-1.54)
0.72
Basophils, x109/L
0.00 (0.00-0.02)
0.00 (0.00-0.00)
0.00 (0.00-0.03)
0.42
Lymphocytes, x109/L
1.22 (0.80-1.90)
1.21 (0.76-1.85)
1.27 (0.94-1.90)
0.42
Platelets, x109/L
126 (78-172)
114 (73-140)
148 (91-196)
0.0162
Albumin level, g/L
35.7 (30.9-40.2)
35.7 (31.9-39.7)
36.5 (30.8-41.0)
0.52
Tryptase level ≥200 ng/mL
47 (43)
20 (43)
27 (57)
0.33
Alkaline phosphatase level > ULN
48 (67)
24 (50)
24 (50)
0.73
KIT mutation D816V
D816X
Wild-type
100 (92) 3 (3)
5 (5)
46 (46) 2 (67) 4 (80)
54 (54) 1 (33) 1 (10)
0.34 -
Abnormal karyotype
10 (15)
6 (60)
4 (40)
0.74
SRSF2/ASXL1/RUNX1 No S/A/R mutations >1 S/A/R mutations
42 (51) 40 (49)
14 (33) 22 (55)
28 (67) 18 (45)
0.0483
CD25
107 (99)
52 (49)
55 (51)
>0.94
MARS category Low-risk Intermediate-risk High-risk
28 (31) 20 (22) 43 (47)
9 (32)
9 (45) 24 (56)
19 (68) 11 (55) 19 (44)
0.153 -
ISPM category Low-risk Intermediate-risk 1 Intermediate-risk 2
8 (11) 27 (38) 37 (51)
4 (50) 14 (52) 19 (51)
4 (50) 13 (48) 18 (49)
>0.94 -
Time since diagnosis in months
26 (10-48)
27 (12-45)
24 (9-50)
0.92
Time since start of midostaurin in months
20 (8-42)
19 (8-38)
21 (7-42)
0.92
Deaths
59 (53)
38 (64)
21 (36)
<0.0013
WHO: World Health Organization; ASM: aggressive systemic mastocytosis; SM-AHN: systemic mastocytosis with an associated hematologic neoplasm; MCL: mast cell leukemia; CMML: chronic myelomonocytic leukemia; MDS: myelodysplastic syndrome; MPN: myeloproliferative neoplasm; MDS/MPNu: myelodysplastic syndrome / myeloproliferative neoplasm unclassified; AML: acute myeloid leukemia; allo-HSCT: al- logeneic hematopoietic stem cell transplantation; MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis; IPSM: Interna- tional Prognostic Scoring System; ULN: upper limit of normal. IPSM score includes: age >60 years, tryptase concentration >125 ng/mL, leu- kocytes >16x109/L, hemoglobin <11 g/dL, platelets <100x109/L and skin involvement.16 Response to midostaurin defined according to Valent criteria per physician discretion based on clinical and biological parameters. All KIT sequencing in the midostaurin cohort performed by nested PCR17 or by droplet digital PCR. D816X corresponds to two D816Y and one D816H mutations. 1Median (IQR); N (%). 2Wilcoxon’s test. 3Pearson’s χ2 test. 4Fisher’s exact test. Data were quoted as the median (interquartile range [IQR]) for continuous variables and the frequency (%) for categorical variables. Groups were compared in a non-parametric Wilcoxon test for continuous variables and in a χ2 or Fisher’s exact test (as appropriate) for categorial variables. P<0.05 was considered statistically significant. All statistical analyses were performed using R software (version 4.3.0).
Adv-SM patients than in midostaurin-treated CD2+ Adv- SM patients (32.1 vs. 49.3 months, respectively, P=0.011) (Figure 1A). Next, we assessed the prognostic impact of CD2 expression on patients having received cladribine. We identified 17 patients (including 11 CD2- patients) in the midostaurin cohort who had been treated with cladribine prior to the initiation of midostaurin. The median TTF was significantly lower in CD2- patients than in CD2+ patients (3.4 vs. 7.0 months, respectively, P=0.043) (Figure 1B). Lastly, we studied the prognostic impact of CD2 expression on OS in a multivariable analysis with the other MARS labo-
ratory parameters (Online Supplementary Table S2). In a univariable analysis, WHO classification, platelet count, hemoglobin level, SRSF2 / ASXL1 / RUNX1 mutations, and CD2 expression were associated with poor OS. However, in a multivariable analysis, only the platelet count was still associated with poor OS (Hazard Ratio=0.99, P=0.005). Our study provides valuable diagnostic and prognostic information. All patients with a non-TKD genotype lacked CD25 expression on their BMMC. Therefore, the absence of these immunophenotypic and molecular criteria (i.e., TKD mutation) may prompt physicians to screen for other KIT
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