KIT D816V Positive Acute Mast Cell Leukemia Associated with Normal Karyotype Acute Myeloid Leukemia

Table 2

Clinical and laboratory features observed in our patient with MCL + AML, as compared to those described in a review of 51 cases of MCL performed by Georgin-Lavialle et al. in 2013 [8], and in a series of 28 patients with MCL published by Jawhar et al. in 2017 [22].

	Georgin-Lavialle et al. review [8]			Jawhar et al. series [22]			This case (MCL-AML)
	MCL (n = 51)	De novo MCL (n = 30)	Secondary MCL (n = 11)	MCL (n = 28)	De novo MCL (n = 16)	Secondary MCL (n = 12)
Demographic data
Age, years	52 (5–76)	52 (18–76)	35 (5–75)	67 (45–82)	69 (47–82)	65 (45–73)	41
Gender, males/females	20 (40)/30 (60)	11 (38)/18 (62)	6 (55)/5 (45)	16 (57)/12 (43)	10 (63)/6 (37)	6 (50)/6 (50)	Female
Diagnosis
MCL (without AHN)	36/40 (90)	27 (89)	11 (100)	8 (29)	6 (38)	2 (17)	No
MCL-AHN (other than AML)	4/40 (10)	3 (11)	0 (0)	20 (71)	10 (62)	10 (83)	No
MC disorder prior to MCL	11 (40)	0 (0)	11 (100)	12 (43)	0 (0)	12 (100)	Probably yes
ASM	NA	NA	NA	2 (7)	0 (0)	2 (17)	No
SM-AHN	NA	NA	NA	10 (36)	0 (0)	10 (83)	No
Leukemic MCL (MC in the PB ≥ 10%)	18/47 (38)	15 (50)	3 (30)	2 (7)	NA	NA	Yes (20)
Peripheral blood findings
Tryptase, μg/L	433 (21–2357)	433 (21–742)	250 (173–2357)	520 (157–1854)	520 (157–1854)	544 (160–1250)	184 μg/L
Tryptase > 200 μg/L	NA	NA	NA	26 (93)	15 (94)	11 (92)	No
Cytopenias	NA	NA	NA	26 (93)	15 (94)	11 (92)	Yes
Hemoglobin, gr/dl	9.9 (5.4–14.0)	9.0 (5.4–13.7)	11.0 (8.1–13.3)	8.9 (7.9–14.3)	9.2 (7.9–13.3)	8.7 (7.9–14.3)	11.0
Neutrophils, ×10^9/L	3.7 (1.0–15.3)	6.0 (1.0–14)	NA	NA	NA	NA	0.3
Platelets, ×10^9/L	110 (5–318)	82 (5–202)	111 (30–150)	69 (21–795)	64 (21–795)	86 (26–331)	16
Hypoalbuminemia < 35 g/L	NA	NA	NA	11 (39)	5 (31)	6 (50)	Yes (32 g/L)
Alkaline phosphatase > 150 U/L	NA	NA	NA	20 (71)	10 (62)	10 (62)	Yes (731 U/L)
% Mast cells	6 (0–72)	7 (0–72)	0 (0–12)	NA	NA	NA	21%
Other relevant findings
Splenomegaly	38/49 (65)	23 (82)	9 (82)	28 (100)	16 (100)	12 (100)	Yes
Hepatomegaly	32/47 (68)	21 (78)	6 (60)	NA	NA	NA	Yes
Skin lesions	15/50 (30)	4 (14)	5 (45)	NA	NA	NA	Yes
Ascites	9/50 (18)	5 (17)	1 (9)	13 (46)	7 (44)	6 (50)	Yes
Asthenia	NA (78)	NA	NA	NA	NA	NA	Yes
Weight loss > 10% in 6 months	NA (38)	NA	NA	12 (43)	8 (50)	4 (33)	NA
Anorexia	NA (20)	NA	NA	NA	NA	NA	Yes
Flushing and other MCAS	39/50 (78)	24 (83)	8 (73)	NA	NA	NA	Yes
Bone marrow findings
% MC in BM smears	NA	NA	NA	25 (20–95)	25 (20–95)	20 (20–95)	16
% MC in BM biopsy	50 (20–100)	60 (20–100)	60 (25–90)	65 (20–95)	60 (20–95)	65 (30–95)	NA
Phenotypic aberrancies
CD2+	15/29 (52)	6 (46)	1	NA	NA	NA	No
CD25+	18/24 (75)	6 (50)	3	NA	NA	NA	Yes
Molecular and chromosomal aberrancies
KIT D816V mutation	13/28 (46)	6 (40)	1 (20)	16 (68)	10 (63)	9 (75)	Yes
Other KIT mutations	6/28 (22)	3 (19)	3 (60)	6 (21)	4 (25)	2 (17)	NA
SRSF2, ASXL1, or RUNX1 mutations	NA	NA	NA	13 (52)	7 (50)	6 (55)	NA
Normal karyotype	20/23 (83)	8 (73)	NA	19 (79)	11 (79)	8 (10)	Normal
Survival and leukemic transformation
Survival, months	6 (0.5–98)	4 (0.5–24)	5 (1–18)	17 (1–86)	NA	NA	>24
Progression into secondary AML	NA	NA	NA	3 (11)	2 (13)	1 (8)	MCL + AML
Deaths	33/48 (69)	24 (83)	5 (62)	18 (64)	10 (63)	8 (67)	Alive

AHN, associated hematological neoplasm; AML, acute myeloid leukemia; BM, bone marrow; CEL, chronic eosinophilic leukemia; CM, cytomorphology; CMML, chronic myelomonocytic leukemia; MC, mast cells; MCAS, mast cell activation-related symptoms; MCL, mast cell leukemia; MCL-AHN, mast cell leukemia with associated hematological neoplasm; MDS, myelodysplastic syndrome; MDS/MPN, myelodysplastic myeloproliferative neoplasm; NA, not available or not evaluated. Results are presented as median (range) values or as number (percentage) of patients with the mentioned characteristic. Not all parameters were evaluated in all patients. AHN included MDS (n = 3) and CMML (n = 1) in the Georgin-Lavialle review, and CMML (n = 8), MDS/MPN unclassifiable (n = 5), MDS (n = 5) or CEL (n = 2) in the Jawhar series. Our patient had past history of uninvestigated maculopapular skin lesions and flushing episodes, and a maculopapular rash at the diagnosis (skin biopsy not performed). In the Jawhar series, karyotype was available in 24 patients with MCL (14 patients with de novo MCL and 10 patients with secondary MCL); 5 patients (21%) had an aberrant karyotype (3 patients with de novo MCL, 21%; 2 patients with secondary MCL, 20%), with 3 patients having a complex karyotype (≥3 aberrations) and 2 patients having del(5q) or del(12p), respectively. Cytogenetic studies were available for 23 of 51 cases reviewed by Georgin-Lavialle et al., and a normal karyotype was found in 83% cases (83%). Two patients (9%) had a 5q deletion and were diagnosed as having MCL-MDS, and 2 patients with de novo MCL had t(10;16)(q22;q13q22) and t(8;21)(q22;q22). Thus, there are no recurrent cytogenetic abnormalities in MCL. Three patients from the Jawhar series progressed into secondary AML 18, 28, and 34 months, respectively, after the diagnosis of MCL had been established.