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NGS in the management of myeloid malignancies
Table 2. Diagnostic assessment. Suspected diagnosis before NGS testing
ICUSwod (n=21
ICUSwtd (n=16) MPN/MDS (n=16) Aplasia/hypoplasia (n=16) Suspicion of MPN (n=25)
Total n=94
Clonal hematopoiesis
n=8 (CCUS)
n=3 (MDS)
n=7 (CMML)
n=6 (clonal hypoplasia or hMDS)
n=7 (MPN)
31(33%)
No clonal hematopoiesis (N=63)
Diagnosis ruled out
n=13 (MDS)
n=12 (MDS)
n=8 (MPN/MDS)
n=10 (MDS)
n=4 (MPN)
47 (50%)
Diagnosis not ruled out
n=0
n=1
n=1
NA
n=14 (MPN)
16 (17%)
NGS: next-generation sequencing; ICUSwod: idiopathic cytopenia of undetermined significance without dysplasia; ICUSwtd: idiopathic cytopenia of undetermined significance with dysplasia; CCUS: clonal cytopenia of undetermined significance; MPN/MDS: myeloproliferative neoplasm/myelodysplastic syndrome; hMDS: hypoplastic myelodysplasia; MPN: myeloproliferative neoplasm.
Table 3. Prognostic evaluation according to the pathology.
Diagnosis MDS MPN/MDS AA MPN Total n n n n n(%)
Prognosis assessment
Prognostic somatic mutation detected
Theranostic modification
40 29 6 20
14* 11† 1‡ 5**
8 6 0 4
95 (100) 31 (33) 18 (19)
*Eight patients with high-risk mutations (HR) and six patients with low risk mutations (LR); †Ten HR and one LR; ‡One HR; **Five HR. MDS: myelodysplastic syndrome, MPN: myeloproliferative neoplasm; AA: aplastic anemia.
Table 4. Patients in whom therapy was changed in the light of the next-generation sequencing data.
Patient
#71
#2 #4
#65 #32
#42 #51 #7
#17
#161 #16
#120 #145 #90 #104
#93
#5
#124
Pathology
CMML-0
CMML CMML
CMML CMML-2
CMML-2 PMF SMF
SMF
SMF MDS-MLD
MDS-MLD
MDS-MLD MDS-RS-MLD MDS-RS-MLD
MDS-RS-SLD
MDS-SLD
MDS-SLD
Sex Age Risk* (years)
F 67 Int
M 39 Low M 63 Low
M 58 Int M 70 High
F 65 Low M 58 Int F 51 Int
F 45 Int
M 67 Low M 71 Int
F 69 Low M 67 Low M 57 Low F 68 Low
M 44 Low
F 55 Int
F 57 Int
Prognostic Other VUS Therapeutic mutations mutations impact
ASXL1 CBL U2AF1, ASCT
ASXL1 ASXL1
SF3B1 ASXL1
ASXL1 ASXL1, EZH2
ASXL1 ASXL1
EZH2, ASXL1 SF3B1 EZH2 RUNX1
ASXL1
TP53, ASXL1, SF3B1
RUNX1, KRAS TET2, U2AF1, TP53, CBL,
EZH2†, JAK2 and SETBP1 KIT D816V RUNX1, SRSF2, TET2†
TET2 SETBP1 JAK2
TET2
JAK2 V617F ASXL1
STAG2, TET2† TET2 and ZRSR2
BCOR, U2AF1 U2AF1
TET2 DNMT3A
NR3C1
RUNX1, TET2
SETBP1, KDM6A
Second ASCT ASCT
Therapeutic abstention
ASCT after partial response to HMA and high-risk mutation
ASCT
ASCT
Switch from ASCT to the association of ruxolitinib and hydroxyurea
Switch from ASCT to hydroxyurea followed by anagrelide then interferon
ASCT
Switch from lenalidomide to HMA
ASCT Therapeutic abstention ASCT
ASCT after evolution to
MDS-EB1
ASCT
ASCT Therapeutic abstention
SETBP1
*Risk assessed according to the relevant scoring systems: the Revised International Prognostic Scoring System (R-IPSS) for myelodysplastic syndromes, the chronic myelomono- cytic leukemia (CMML)-specific Prognostic Scoring System (CPSS) or Itzykson score for CMML, the Dynamic International Prognostic Scoring System (DIPSS) for primary myelofibrosis and MYSEC for secondary myelofibrosis. †Double mutations of the gene.VUS: variant of undetermined significance; F: female; M: male; Int: intermediate risk; ASCT: allogeneic stem cell transplantation; HMA: hypomethylating agent; PMF: primary myelofibrosis; SMF: secondary myelofibrosis; MDS-MLD: myelodysplastic syndrome with multi- lineage dysplasia; MDS-RS-MLD: myelodysplastic syndrome with ring sideroblasts and multilineage dysplasia; MDS-RS-SLD: myelodysplastic syndrome with ring sideroblasts and single lineage dysplasia; MDS-SLD: myelodysplastic syndrome with single lineage dysplasia; MDS-EB1: myelodysplastic syndrome with excess blasts 1.
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