Page 70 - Haematologica3

V.B. Pastor et al.
nia during infancy and suffered from self-limiting seizures during infancy with no structural brain abnormalities or neurological deficits identified. Peripheral blood findings at diagnosis included isolated thrombocytopenia in one (P2), thrombocytopenia with neutropenia in two (P1, P3) and pancytopenia in four patients (P4-7). Mean corpuscular vol- ume was increased in five of the seven patients at diagno- sis, and HbF was elevated in two out of three tested patients. MDS manifested at the median age of 2.1 (range, 1.0-42) years as hypocellular refractory cytopenia of child- hood (RCC) or in the adult (P6) as refractory cytopenia with multilineage dysplasia (Table 1). Severe dysplasia with vacuolization was observed in two patients (P1, P2). A common cytogenetic feature in all patients was the com- plete or partial loss of chromosome 7 (Table 1).
Table 1. Clinical data of SAMD9L-mutated patients.
The clinical course was remarkable for several patients. Three years after the initial diagnosis of RCC, P1 devel- oped severe infections and hepatosplenomegaly, and for the first time required platelet transfusions, while his blood smear showed 21% blasts, compatible with the diagnosis of CMML (with no in vitro hypersensitivity to granulocyte-macrophage colony-stimulating factor), (Figure 2). Following hematopoietic stem cell transplanta- tion, he developed late-onset acute graft-versus-host dis- ease and died from cerebral hemorrhage. At the same time, his younger sister (P2) was diagnosed with RCC/-7; however, the parents decided against follow-up in the hematology clinic. Unexpectedly, her complete blood count normalized 3.7 years later and remained stable until the last follow-up 20 years after the initial diagnosis. She
Patient # Gestational age; (UPN); measurements
Dysmorphic features, neurol. symptoms
none
none
none
none
none
none none
Prior medical problems
Timepoint; MDS subtype
3.4 yrs; RCC
7 yrs; progress: CMML
2.0 yrs; RCC
5.7 yrs
12 yrs
13 yrs
14, 15, 17, 18 yrs 22 yrs
12 mo; RCC
13 mo 15 mo 17 mo 18.5 mo
7.7 yrs; RCC
PB findings
(Plt, WBC, ANC: x109/L; Hb: g/dL)
Cellularity
BM findings Dysplasia
Cytogenetics
Blasts (%) Metaphases FISH chr. 7
<5 45,XY,-7 [6] / 60% 46,XY [10]
5 45,XY,-7 [5] 95%
sex
P1 (D084); male
P2 (D154); female
P3 (US1); female
P4 (US2); male
(percentile)
39w: 3550g (P>50-75), 50cm (P20)
34w: 2670g (P75-90), 49cm (P90)
40w: 4080g (P90-97), 53cm (P50)
41w: 3540g (P25-50), 52cm (P40)
recurrent RTI
and endogenous eczema since infancy, transient pancytopenia at 6 mo, Plt , ANC
at 2 yrs; self-limiting seizures at 3 yrs
recurrent RTI since age 1.5 yrs
endogenous eczema
recurrent RTI and endogenous eczema since infancy
none
none
pancytopenia and hypocellular
Plt↓ (41), WBC↓ /ANC↓ ↓ +++ (4.3/0.34), MCV↑ vacuolization
in E+M Plt↓, WBC (mono: N +++
21%, blasts: 10%, erythro-blasts: 26%)
Plt (96), MCV ↓ +++ vacuolization in M
<5 45,XX,-7‡
n.p. n.p <5 46,XX <5 n.p. <5 46,XX
n.p. n.p.
<5 45,XX,-7 [3] 46,XX [18]
<5 46,XY [20]
7 46,XY [20] <5 46,XY [20] <5 n.p.
77%
n.p
n.p normal normal n.p.
/ 16%
normal
normal 5.5% 15%
normal, MCV↑ n.p. n.p. normal, MCV↑ N + normal, MCV↑ N N normal, MCV↑ N N normal, MCV↑ n.p. n.p.
20 mo; RCC
Plt↓ (88), ANC↓ ↓ + (0.54), MCV ↑
Plt↓ (5), ANC↓ ↓ ++ (0.43), Hb↓ (8.3),
HbF↑ (5.2%)
ANC↓ (0.88), Hb↓ (9.8) N N
normal N N normal, HbF↑ (11.3%) N N ANC (0.6) N N
Plt↓ (64), WBC↓/ANC ↓ ++ (1.7/0.08), Hb↓ (9.8),
MCV↑, HbF↑ (5.7%)
<5
45,XY,-7 [6] 46,XY,del(7) (q11.2q36) [4] / 46,XY [10]
/ 19%
P5 (D637);40w: 3875g (P75),
<5 45,XY,-7,der(18;21) n.p. (q10;q10),+21 [20/20]
<5 45,XY,der(1;7)(q10; n.p. p10)[11]/ 46,XY[5]
male
P6 (D637f); male
P7 (SC054); female
54cm (P75)
term: normal
term: normal
42yrs;RCMD Plt↓(72),WBC↓/ANC↓ ↓ ++ (2.0/1.4), Hb↓ (5.8), MCV↑
430
2.1 yrs; RCC
2.3 yrs 5, 6, 7.5, 11, 12, 18 yrs
Plt↓ (74), WBC↓/ANC↓ N + (4.0/0.8), Hb↓ (10.2)
<5 45,XX,-7 [4] / 46,XX [17] <5 46,XX [25]
<5 normal
-7 confirmed normal normal
Plt↓ (90), Hb↓ (10.5) + normal, HbF↑ N N
(1.2-2.8%)
UPN: unique patient number; syndr.: syndromic; w: gestational week; RTI: respiratory tract infection (including otitis, bronchitis, pneumonia); yrs.: years of age; mo: months of age; Dx: diagnosis; RCC: refractory cytopenia of childhood; CMML: chronic myelomonocytic leukemia; BM: bone marrow; E: erythropoiesis, M: myelopoiesis; n.p.: not performed; PB: peripheral blood; Plt: platelets; MCV: mean corpuscular volume (according to age);WBC:white blood count;ANC:absolute neutrophil count;Dysplasia:+,mild;++,moderate;+++,severe.N,normal;FISH: fluorescence in situ hybridization;*with occasional small dysplastic megakaryocytes. ‡ 51% of metaphases with monosomy 7, of those 17% additionally showed hypoploid metaphases with involvement of chromosomes 9, 14, 19, 21.
haematologica | 2018; 103(3)