Page 231 - Haematologica Vol. 110 - January 2025

LETTER TO THE EDITOR
(N=58, 79.4%) expressed CD25. In contrast, only 9 of the 14 patients (64.3%) without a KIT TKD mutation were CD25+. Specifically, 3 patients with a WT KIT (1 with ISM, 1 with SM- AHN, and 1 with MCL) and 2 patients with a juxtamembrane mutation (1 MCL and 1 MCS) were CD25- (Online Supplemen- tary Figure S1A). One patient with MCL initially displayed a juxtamembrane KIT mutation (Dup 501-502) with CD25- BMMC. However, after masitinib therapy (targeting WT and juxtamembrane KIT mutations) and remission, the patient relapsed and showed two different BMMC populations: one CD25+ and the other CD25- (Online Supplementary Figure S1B). This phenotypic mosaicism was confirmed by immu- nochemistry, and the appearance of CD25 coincided with the detection of a sub-clonal KIT D816 mutation. Sorting of CD25+ BMMC confirmed that the KIT D816H mutation was restricted to this compartment and was absent from the
CD25- population.
Expression of CD2 on BMMC was significantly more fre- quent in non-Adv-SM patients (45/50, 90%) than in Adv-SM patients (13/23, 57%, P=0.003) (Online Supplementary Table S1). To specifically investigate the association between a lack of CD2 expression on BMMC and the characteristics and outcomes of patients with Adv-SM, we retrospectively constituted a cohort of 111 midostaurin-treated patients, of whom 53 (47.7%) were CD2- (Table 1). CD2- patients were more likely to be male (81%, vs. 64% of CD2+ patients, P=0.042) and to present with a low platelet count (114 vs. 148x109/L, respectively, P=0.016), have adverse additional mutations (i.e., SRSF2 / ASXL1 / RUNX1; 61%, vs. 39%, re- spectively, P=0.048), and were more likely to die (72%, vs. 36%, respectively, P<0.001). Accordingly, the median OS time was significantly lower in midostaurin-treated CD2-
Table 1. Characteristics of the patients with advanced systemic mastocytosis, according to their expression of CD2 on bone marrow mast cells.
Variable
CD2 expression
Overall N=1111
Negative N=531
Positive N=581
P
Age in years
68 (60-76)
70 (65-76)
68 (59-74)
0.32
Male sex
80 (72)
43 (81)
37 (64)
0.0423
WHO classification ASM
MCL SM-AHN
27 (24) 9 (8) 75 (68)
10 (37) 3 (33) 40 (53)
17 (63) 6 (67) 35 (47)
0.34 -
AHN subtypes CMML
MDS
MPN MDS/MPNu
34 (45) 23 (31) 6 (8.0) 12 (16)
17 (50) 15 (65) 2 (33) 6 (50)
17 (50) 8 (35) 4 (67) 6 (50)
0.54 -
AML transformation
21 (28)
13 (62)
8 (38)
0.43
AHN progression
20 (28)
14 (70)
6 (30)
0.133
Allo-HSCT
14 (13)
7 (50)
7 (50)
0.93
Hepatomegaly
72 (71)
33 (46)
39 (54)
0.63
Splenomegaly
85 (83)
42 (49)
43 (51)
>0.93
Adenopathy
59 (65)
26 (44)
33 (56)
0.33
Cutaneous mastocytosis
52 (53)
20 (39)
32 (61)
0.0593
Portal hypertension - ascites
40 (38)
22 (55)
18 (45)
0.33
Malabsorption, weight loss
67 (64)
38 (57)
29 (43)
0.0353
Osteolytic lesions
29 (28)
15 (52)
14 (48)
0.73
Response to midostaurin
60 (58)
31 (52)
29 (48)
0.43
Causes of midostaurin discontinuation allo-HSCT
Relapse/refractory
Intolerance
4 (5) 60 (74) 17 (21)
2 (50) 35 (58) 5 (29)
2 (50) 25 (42) 12 (71)
0.104 -
Hemoglobin, g/dL
10.10 (9.12-11.90)
9.95 (8.60-11.70)
10.25 (9.30-12.35)
0.32
Leukocytes, x109/L
8 (4-13)
8 (5-13)
7 (4-11)
0.32
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