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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

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2018 Impact Factor: 1.847

Front. Med.    2020, Vol. 14 Issue (3) : 327-334    https://doi.org/10.1007/s11684-019-0712-x
RESEARCH ARTICLE
Clinical characteristics and prognostic values of 1p32.3 deletion detected through fluorescence in situ hybridization in patients with newly diagnosed multiple myeloma: a single-center study in China
Huanping Wang1,2, Haitao Meng1,2, Jinghan Wang1,2, Yinjun Lou1,2, Yile Zhou1, Peipei Lin3, Fenglin Li1, Lin Liu1,2, Huan Xu1,2, Min Yang1,2, Jie Jin1,2()
1. Institute of Hematology, Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
2. Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, Zhejiang Province, Hangzhou 310003, China
3. Department of Hematology, Taizhou Central Hospital, Taizhou 318000, China
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Abstract

This study aimed to investigate the prevalence, clinical characteristics, and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM). A retrospective analysis was conducted on 411 patients with newly diagnosed MM; among which, 270 received bortezomib-based therapies, and 141 received thalidomide-based therapies. Fluorescence in situ hybridization (FISH) was performed to detect six cytogenetic abnormalities, namely, del(1p32.3), gain(1q21), del(17p13), del(13q14), t(4;14), and t(11;14). Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells (P = 0.025), higher β2-microglobulin levels (P = 0.036), and higher lactate dehydrogenase levels (P = 0.042) than those without del(1p32.3). Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies (median PFS 11.6 vs. 31.2 months, P = 0.002; median OS 16.8 vs. 45.9 months, P <0.001) were strongly associated with short progression-free survival (PFS) (P = 0.002) and overall survival (OS) (P <0.001). Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS (P = 0.006) and OS (P = 0.016) for patients under thalidomide-based treatments. Patients with del(1p32.3) under bortezomib-based treatments tended to have short PFS and OS. In conclusion, del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide- or bortezomib-based treatments.

Keywords 1p32.3 deletion      1q21 gain      prognosis      multiple myeloma      FISH      bortezomib      thalidomide     
Corresponding Author(s): Jie Jin   
Just Accepted Date: 11 September 2019   Online First Date: 29 November 2019    Issue Date: 08 June 2020
 Cite this article:   
Huanping Wang,Haitao Meng,Jinghan Wang, et al. Clinical characteristics and prognostic values of 1p32.3 deletion detected through fluorescence in situ hybridization in patients with newly diagnosed multiple myeloma: a single-center study in China[J]. Front. Med., 2020, 14(3): 327-334.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-019-0712-x
https://academic.hep.com.cn/fmd/EN/Y2020/V14/I3/327
Characteristics All patients del(1p32.3) positive del(1p32.3) negative P value
Patients, n (%) 411 34 377
Age (year); median (range) 62 (27–85) 64.5 (39–83) 62 (27–85) 0.806
Gender 0.205
?Male, n (%) 246 (59.9) 24 (70.6) 222 (58.9)
Female, n (%) 165 (40.1) 10 (29.4) 155 (41.1)
ISS (n = 405) 0.053
I 119 (29.4%) 9 (30.0%) 110 (29.3%)
II 140 (34.6%) 5 (16.7%) 135 (36.0%)
III 146 (36.0%) 16 (53.3%) 130 (34.7%)
BM Plasma cells (%); median (range) 26 (0–98) 40 (3–92) 24.5 (0–98) 0.025
Calcium (mmol/L); median (range) 2.25 (1.61–3.71) 2.36 (1.77–3.55) 2.24 (1.61–3.71) 0.235
b2-microglobulin (mg/L); median (range) 3.88 (0.73–76.63) 5.53 (2.0–76.63) 3.80 (0.73–39.08) 0.036
Creatinine (mmol/L); median (range) 80 (8–2013) 95 (43–923) 80 (8–2013) 0.166
LDH (U/L); median (range) 185 (59–1023) 232 (79–694) 183 (59–1023) 0.042
Ig isotype (n = 410) 0.173
IgG 197 (48.0) 13 (39.4) 184 (48.8)
IgA 107 (26.1) 9 (27.3) 98 (26.0)
IgM 4 (1.0) 1 (3.0) 3 (0.8)
IgD 12 (2.9) 2 (6.1) 10 (2.7)
Light chains 81 (19.8) 6 (18.2) 75 (19.9)
Nonsecretory 9 (2.2) 2 (6.1) 7 (1.9)
gain(1q21) (%) 222 (54) 192 (50.9) 30 (88.2) <0.001
del(17p) (%) 30 (7.3) 21 (26.5) 9 (5.6) <0.001
del(13q) (%) 157 (38.2) 138 (36.6) 19 (55.9) 0.041
t(11;14) (%) 33 (8.0) 31 (8.2) 2 (5.9) 1.000
t(4;14) (%) 34 (8.3) 32 (8.5) 2 (5.9) 1.000
Treatment 1.000
Bortezomib-based therapies 270 (65.7) 248 (65.8) 22 (64.7)
Thalidomide-based therapies 141 (34.3) 129 (34.2) 12 (35.3)
Tab.1  Baseline clinical and biological characteristics of the evaluated patients with newly diagnosed MM
Risk factors PFS OS
HR (95% CI) P value HR (95% CI) P value
del(1p32.3) 1.933 (1.260–2.966) 0.003 2.156 (1.324–3.511) 0.002
gain(1q21) 1.863 (1.396–2.486) <0.001 2.176 (1.501–3.154) <0.001
del(17p) 1.629 (1.034–2.566) 0.035 2.626 (1.625–4.244) <0.001
del(13q) 1.588 (1.202–2.099) 0.001 1.449 (1.023–2.052) 0.037
t(11;14) 1.836 (1.166–2.891) 0.009 1.806 (1.054–3.096) 0.032
t(4;14) 1.560 (0.992–2.453) 0.054 1.487 (0.837–2.641) 0.176
ISS III 1.499 (1.129–1.991) 0.005 2.966 (2.085–4.219) <0.001
Cr≥177 mmol/L 1.949 (1.361–2.792) <0.001 3.483 (2.310–5.252) <0.001
Ca≥2.75 mmol/L 1.551 (0.942–2.553) 0.084 2.292 (1.310–4.008) 0.004
LDH≥240 U/L 1.523 (1.129–2.053) 0.006 1.602 (0.935–2.746) 0.086
Age≥65 0.951 (0.718–1.260) 0.728 1.329 (0.941–1.878) 0.106
Tab.2  Univariate analysis of risk factors on PFS and OS in patients with newly diagnosed MM
Fig.1  Impact of cytogenetic abnormalities on PFS and OS.
Fig.2  PFS and OS of patients with or without del(1p32.3) under thalidomide-based therapies.
Fig.3  OS of del(1p32.3)-positive patients under bortezomib-based or thalidomide-based therapies.
Risk factors PFS OS
HR (95% CI) P value HR (95% CI) P value
del(1p32.3) 3.083 (1.379–6.894) 0.006 2.478 (1.187–5.173) 0.016
gain(1q21) 2.019 (1.042–3.914) 0.037 1.509 (0.886–2.570) 0.130
del(17p) 2.134 (0.784–5.808) 0.138 2.680 (1.507–4.767) 0.568
Tab.3  Multivariate analysis of genetic variables associated with PFS and OS in thalidomide-based therapies
Risk factors PFS OS
HR (95% CI) P value HR (95% CI) P value
del(1p32.3) 1.263 (0.644–2.476) 0.497 0.626 (0.262–1.494) 0.291
gain(1q21) 1.702 (1.119–2.588) 0.013 2.536 (1.448–4.441) 0.001
del(17p) 1.330 (0.708–2.498) 0.376 3.255 (1.593–6.653) 0.001
t(11;14) 2.035 (1.162–3.564) 0.013 1.477 (0.743–2.937) 0.266
Tab.4  Multivariate analysis of genetic variables associated with PFS and OS in bortezomib-based therapies
Fig.4  PFS and OS of patients with MM without cytogenetic lesions, with one lesion, and with more than one lesion.
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