Page 46 - Haematologica August 2018

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blood count was abnormal in 36 patients (73%): 24 patients (49%) had monocytopenia lower than 0.1 G/L, 19 patients (39%) had neutropenia lower than 1.5 G/L, 9 patients (18%) had platelet levels lower than 100x109/L, 7 patients (14%) had macrocytosis, and 5 patients (10.2%) had anemia lower than 9 g/dL (Online Supplementary Figure S1). Consequently, 36 out of these 49 evaluable patients (73%) had an abnormal blood count.
Immunological data were available in 38 patients: T-cell counts were slightly decreased (median 0.97 G/L T CD3 (range, 0.1-7.5), 0.37 G/L T CD4 (range, 0.05-5.6), and 0.49 G/L T CD8 (range, 0.02-2.3), NK cells (CD16+/CD56+) were preserved (median 0.12 G/L, range: 0-0.34); B-cell levels were consistently low (median 0.02 G/L, range, 0- 1.51) although immunoglobulin levels were within normal ranges (median IgG=9.3 g/L, range, 4-40; IgA=0.9 g/L, range, 0.33-3.4; IgM=1 g/L, range, 0.05-2.40). Overall, GATA2 defects are mainly associated with a monocytope- nia and a B-cell lymphopenia.
More than 80% of patients presented with
a hematologic malignancy at the age of 40 years
Among the 74 symptomatic patients, 64 developed a hematologic malignancy (MDS and/or AL). The risk of developing MDS/AL rapidly increased from 6% at the age of10yearsto39%attheageof20,and81%attheageof 40 (Figure 1B). Among the 64 patients, the initial diagnosis was MDS in 55 patients (69%), AL in 7 patients (9%), and chronic leukemia in 2 patients (3%). Among the 55 patients with an MDS, a progression to AL was observed in 9 patients (16%) (Figure 2A). The AL were mainly myeloid (AML), but we observed a case of T-cell acute
lymphoblastic leukemia with a monosomy 7. In addition to these hematologic complications, a juvenile myelo- monocytic leukemia (JMML) case occurred in a neonate. This patient received neither chemotherapy nor allograft. This patient’s blood count is normal four years after diag- nosis without any treatment.
Karyotypes were abnormal in 43 of 66 patients (65%), with a complete or a partial loss of chromosome 7 in 27 cases (35%), trisomy-8 in 16 cases (18%), 4 patients com- bining the two (Figure 2B).
In order to better define the prognosis of MDS, the IPSS- R21 was calculated for 47 of 55 patients upon diagnosis of MDS. The prognosis was mainly intermediate (1.5-4.5) in 24 patients (51%), high (>4.5) in 13 patients (27%), and low (<1.5) in 10 patients (21%). There was no significant difference in the age of the patients between these 3 groups.
Low frequency of solid neoplasia
Solid tumors were identified in 6 patients only, mainly secondary to HPV (3 cases). In addition, one woman developed breast cancer, one patient developed a metasta- tic adenocarcinoma, and one patient developed an epider- moid carcinoma.
Severe infectious diseases explain the high mortality
Severe bacterial infections were the most frequent fea- ture, occurring at some time over the patients’ lives in 44 cases (56%). The 20-year cumulative rate of bacterial infection was 33%, rising to 64% at the age of 40 years (Figure 1E). Lung infections were the most frequent (two-thirds of all cases) and, although they evolved
AB
C
Figure 2. Hematologic features of the 79 patients. (A) Hematologic malignancies among the 79 patients. Progression to acute myeloid leukemia (AML) from myelodysplastic syndromes (MDS) is indicated. (B) Karyotypes availables for 66 out of 79 GATA2-deficient patients. *4 patients with monosomy 7 also had trisomy 8. (C) Hematologic complications and the outcome of patients older than the age of 40. JMML: juvenile myelomonocytic leukemia; CMML: chronic myelomonocytic leukemia; LEMP: leukoencephalomyelopathy; HSCT: hematopoietic stem cell transplantation.
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