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Table 1. Chronic myeloid leukemia cases with -7 del(7q) in Philadelphia-negative cells.
Author, year (ref)
Gambacorti-Passeri 20019
Groves 20115
N. of cases /type
1 Del(7)(q22q23)
53 (including 6 AP) -7 (29) -7+8(14) Del7q (10)
N. with other CCA/Ph-
1 +8
14 +8
2
+8 None
+8 (19.5%)
TKI
Imatinib
Nilotinib Imatinib Dasatinib
Imatinib
Dasatinib
Nilotinib
Imatinib Dasatinib Nilotinib Ponatinib
Imatinib Dasatinib Nilotinib Bosutinib Ponatinib
Previous
TT MDS AML
Yes IFN No No
Yes IFN 7 9
Yes Yes Yes IFN
Imatinib No No
Onset of CCA/Ph-
6 months
10 months 2.8-53)
5 years
6 months
Outcome
NA
AML alive 1/9 MDS alive 6 1NA
Died of AML
-8 years MMR
-AlloBMT alive
Karimata
201111 -7
Wasilewska 2
20176 -7
Issa 4 20177 -7
Bidet 26 20198 -7
1
No 1 1 9months 5yearsOS 37% (95%CI: 1-80)
Yes (50%° of Pts) IFN
50%
No
-1 died of BC -1 died post allo BMT for AML
-1 MDS in MR4.5 on bosutinib -1 MR 4.5
on imatinib
2.08 years (0.8-12.65) Worse EFS and PFS Same OS
N:number;CCA:clonalchromosomalabnormalities; Ph:Philadelphia;TKI:tyrosinekinaseinhibitor;TT:therapy;MDS:myelodysplasticsyndrome;AML:acutemyeloidleukemia; IFN: interferon; NA: not available; AP: accelerated phase; MR: molecular response;MMR: major molecular response; alloBMT: allogeneic bone marrow transplantation; Pts: patients; BC: blast crisis; EFS: event-free survival; PFS: progression-free survival; OS: overall survival.
TKI therapy. Patients were selected from French centers of the French CML group. They screened 102 CML patients with CCA/Ph-, of these 26 had an abnormality of chromo- some 7 [-7/del(7q)]. A control group of 11 MDS patients, four with 7 [-7/del(7q)], was obtained for comparison. All karyotypes were reviewed by the Groupe Francophone de Cytogenetique Hematologique (GFCH) members and then classified according to the International System for Human Cytogenetic Nomenclature (ISCN 2016), molecu- lar monitoring being performed according to the ELN rec- ommendations. Importantly, BM smears were assessed by morphological central review in 48 cases. Morphological dysplasia was considered significant when it was observed in 10% or more cells in any hematopoietic lineage with or without excess blasts (>5%). Underlying MDS was documented both by cen- tralized morphological analysis of BM smears and by sequencing a targeted panel of 27 genes frequently altered in MDS and AML performed by a next-generation sequencing (NGS) assay. Chromosome 7 abnormalities were isolated in 13 out of the 26, and associated with +8 in 19.5% of cases. Patients who developed -7/del(7q) CCA/Ph- were significantly younger than other CCA/Ph- abnormalities (mean, 48 vs. 55 years old; P=0.035) and mostly benefit second-generation TKI as first line of treatment. Twelve out of the 26 patients who developed -7/del(7q) CCA/Ph- were in complete cytogenetic response at time of detection. Median follow up since
CCA/Ph- detection was 5.35 (1-14) years for -7/del(7q) and 7.41 (0-15) years for others CCA/Ph- (P≥0.05). MDS signs were more frequent in -7/del(7q) CCA/Ph- patients as compared to other types of CCA/Ph-. Molecular response (MR) was less frequently observed in these patients: 33% (n=4 out of 12) of the -7/del(7q) patients with MDS signs achieved MMR or better versus 75% (9 out of 12) of these patients without MDS signs. Using NGS, MDS morphological features were significantly associated with the presence of mutation. Among the 12 patients with -7/del(7q), 4 presented MDS morphological signs and 3 were mutated. Cumulative incidence of MR4.5 was lower in patients with -7/del(7q). Although type of CCA/Ph- did not impact on overall survival, land- mark analysis at three years after first TKI initiation revealed a strong negative impact of -7/del(7q) CCA/Ph- on event-free survival and progression-free survival.
The study of the French Group reports on the largest cohort with a long follow up (median 6.47 years) of CML patients with -7/del(7q) abnormalities.8 These patients are younger, achieved lower cumulative incidence of MR4.5, and are more frequently associated with dysplastic fea- tures. One patient with -7 CCA/Ph- presented EZH2 mutations and then progressed to advanced CML phase; however, the role of this mutation can only be speculated as it was at low variant frequency.
Considering all the rare cases of -7/del(7q) CCA/Ph- abnormalities reported in the literature (Table 1), it
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