Immunophenotypic Landscape and Prognosis of Diffuse Large B-Cell Lymphoma with MYC/BCL2 Double Expression: An Analysis of A Prospectively Immunoprofiled Cohort
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Clinicopathological Characteristics of Patients
2.2. Immunophenotypic Landscape of DLBCL and HGBL
2.3. Relationship between MYC/BCL2 DE Status and Clinicopathological Features
2.4. Effect of DE Status on Patient Survival after Treatment with R-CHOP
2.5. Prognostic Stratification of DE-DLBCL Patients Treated with R-CHOP
2.6. Validation of Prognostic Stratification of DE-DLBCLs
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. IHC and FISH
4.3. Validation Using Publicly Available Data
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Variables * | DLBCL (n = 417) No. (%) | HGBL (n = 44) No. (%) | p | |
---|---|---|---|---|
Sex | male | 242 (58.0) | 31 (70.5) | 0.146 |
female | 175 (42.0) | 13 (29.5) | ||
Age, years | median ± SD | 62 ± 14.094 | 56 ± 15.055 | 0.002 |
mean ± SD | 61.09 ± 14.094 | 54.18 ± 15.055 | ||
Primary sites | nodal | 191 (45.8) | 18 (40.9) | 0.633 |
extranodal | 226 (54.2) | 26 (59.1) | ||
Ann Arbor stage | 1 | 63 (15.4) | 6 (14.3) | 0.282 |
2 | 100 (24.4) | 8 (19.0) | ||
3 | 72 (17.6) | 4 (9.5) | ||
174 (42.5) | 24 (57.1) | |||
B symptoms | absent | 381 (93.4) | 39 (90.7) | 0.522 |
present | 27 (6.6) | 4 (9.3) | ||
Bulky disease † | absent | 375 (91.7) | 27 (62.8) | <0.001 |
present | 34 (8.3) | 16 (37.2) | ||
ECOG PS | 0 or 1 | 288 (85.2) | 33 (86.8) | 1.000 |
2 or more | 50 (14.8) | 5 (13.2) | ||
Serum LDH | normal | 186 (47.6) | 18 (43.9) | 0.743 |
elevated | 205 (52.4) | 23 (56.1) | ||
No. of extranodal sites | 0 or 1 | 276 (69.0) | 29 (69.0) | 1.000 |
2 or more | 124 (31.0) | 13 (31.0) | ||
BM involvement | absent | 308 (84.8) | 29 (72.5) | 0.068 |
present | 55 (15.2) | 11 (27.5) | ||
IPI | 0-1 low risk | 153 (37.0) | 14 (32.6) | 0.434 |
2, low-int. risk | 107 (25.8) | 8 (18.6) | ||
3, high-int. risk | 86 (20.8) | 13 (30.2) | ||
4-5, high risk | 68 (16.4) | 8 (18.6) | ||
Tx regimen | R-CHOP | 382 (97.9) | 29 (69.0) | <0.001 |
Others | 8 (2.1) | 13 (31.0) | ||
Response to Tx | CR | 273 (86.9) | 26 (81.3) | 0.413 |
non-CR | 41 (13.1) | 6 (18.8) | ||
BCL2 | negative | 191 (47.0) | 20 (51.3) | 0.619 |
positive | 215 (53.0) | 19 (48.7) | ||
MYC | negative | 227 (57.8) | 10 (25.6) | <0.001 |
positive | 166 (42.2) | 29 (74.4) | ||
MYC/BCL2 DE status | non-DE | 280 (72.2) | 21 (56.8) | 0.058 |
DE | 108 (27.8) | 16 (43.2) | ||
CD10 | negative | 289 (74.1) | 16 (41.0) | <0.001 |
positive | 101 (25.9) | 23 (59.0) | ||
BCL6 | negative | 177 (44.8) | 9 (23.1) | 0.01 |
positive | 218 (55.2) | 30 (76.9) | ||
MUM1 | negative | 161 (41.1) | 21 (56.8) | 0.081 |
positive | 231 (58.9) | 16 (43.2) | ||
COO | GCB | 145 (37.3) | 27 (69.2) | <0.001 |
non-GCB | 244 (62.7) | 12 (30.8) |
Variables * | DLBCL | p | ||
---|---|---|---|---|
Non-DE (n = 280) No. (%) | DE (n = 108) No. (%) | |||
Sex | male | 169 (60.4) | 58 (53.7) | 0.251 |
female | 111 (39.6) | 50 (46.3) | ||
Age, years | median ± SD | 62 ± 14.60 | 64 ± 13.08 | 0.040 |
mean ± SD | 60.3 ± 14.60 | 63.6 ± 13.08 | ||
Primary sites | nodal | 126 (45.0) | 52 (48.1) | 0.649 |
extranodal | 154 (55.0) | 56 (51.9) | ||
Ann Arbor stage | 1 | 43 (15.6) | 15 (14.2) | 0.406 |
2 | 69 (25.1) | 21 (19.8) | ||
3 | 49 (17.8) | 16 (15.1) | ||
114 (41.5) | 54 (50.9) | |||
B symptoms | absent | 256 (94.1) | 97 (89.8) | 0.182 |
present | 16 (5.9) | 11 (10.2) | ||
Bulky disease | absent | 249 (91.2) | 101 (93.5) | 0.538 |
present | 24 (8.8) | 7 (6.5) | ||
ECOG PS | 0 or 1 | 198 (86.8) | 70 (80.5) | 0.161 |
2 or more | 30 (13.2) | 17 (19.5) | ||
Serum LDH | normal | 139 (52.7) | 35 (34.3) | 0.002 |
elevated | 125 (47.3) | 67 (65.7) | ||
No. of extranodal sites | 0 or 1 | 185 (69.0) | 69 (65.7) | 0.539 |
2 or more | 83 (31.0) | 36 (34.3) | ||
BM involvement | absent | 208 (84.9) | 79 (83.2) | 0.739 |
present | 37 (15.1) | 16 (16.8) | ||
IPI | 0–1, low | 110 (39.6) | 30 (27.8) | 0.042 |
2, low-int. | 72 (25.9) | 26 (24.1) | ||
3, high-int. | 57 (20.5) | 26 (24.1) | ||
4–5, high | 39 (14.0) | 26 (24.1) | ||
Tx regimen | R-CHOP | 256 (97.7) | 101 (98.1) | 1.000 |
others | 6 (2.3) | 2 (1.9) | ||
Response to Tx | CR | 196 (90.3) | 63 (80.8) | 0.042 |
non-CR | 21 (9.7) | 15 (19.2) | ||
PD or relapse | no | 183 (81.7) | 38 (49.4) | <0.001 |
yes | 41 (18.3) | 39 (50.6) | ||
BCL2 | negative | 179 (63.9) | 0 (0) | <0.001 |
positive | 101 (36.1) | 108 (100) | ||
MYC | negative | 224 (80.0) | 0 (0.0) | <0.001 |
positive | 56 (20.0) | 108 (100) | ||
CD10 | negative | 184 (68.7) | 89 (87.3) | <0.001 |
positive | 84 (31.3) | 13 (12.7) | ||
BCL6 | negative | 115 (42.4) | 46 (45.1) | 0.641 |
positive | 156 (57.6) | 56 (54.9) | ||
MUM1 | negative | 125 (46.5) | 27 (26.5) | 0.001 |
positive | 144 (53.5) | 75 (73.5) | ||
COO | GCB | 122 (45.7) | 17 (16.7) | <0.001 |
non-GCB | 145 (54.3) | 85 (83.3) |
Variables | PFS | OS | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p | HR | 95% CI | p | |
Comparison with risk factors | ||||||
Age | 1.033 | 1.014–1.053 | 0.001 | |||
Sex (female) | 0.669 | 0.425–1.052 | 0.082 | |||
Ann Arbor Stage III/IV | 2.436 | 1.290–4.599 | 0.006 | 2.064 | 1.195–3.565 | 0.009 |
ECOG PS of ≥2 | 2.278 | 1.407–3.687 | 0.001 | |||
Elevated serum LDH | 2.610 | 1.424–4.783 | 0.002 | 4.522 | 2.456–8.328 | <0.001 |
No. of extranodal sites ≥2 | ||||||
MYC/BCL2 DE | 2.885 | 1.707–4.876 | <0.001 | 1.872 | 1.194–2.936 | 0.006 |
Comparison with IPI | ||||||
IPI score of ≥2 | 2.259 | 1.312–3.889 | <0.001 | 3.641 | 2.101–6.312 | <0.001 |
MYC/BCL2 DE | 3.041 | 1.943–4.760 | <0.001 | 2.678 | 1.819–3.941 | <0.001 |
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Han, B.; Kim, S.; Koh, J.; Yim, J.; Lee, C.; Heo, D.S.; Kim, T.M.; Paik, J.H.; Jeon, Y.K. Immunophenotypic Landscape and Prognosis of Diffuse Large B-Cell Lymphoma with MYC/BCL2 Double Expression: An Analysis of A Prospectively Immunoprofiled Cohort. Cancers 2020, 12, 3305. https://doi.org/10.3390/cancers12113305
Han B, Kim S, Koh J, Yim J, Lee C, Heo DS, Kim TM, Paik JH, Jeon YK. Immunophenotypic Landscape and Prognosis of Diffuse Large B-Cell Lymphoma with MYC/BCL2 Double Expression: An Analysis of A Prospectively Immunoprofiled Cohort. Cancers. 2020; 12(11):3305. https://doi.org/10.3390/cancers12113305
Chicago/Turabian StyleHan, Bogyeong, Sehui Kim, Jiwon Koh, Jeemin Yim, Cheol Lee, Dae Seog Heo, Tae Min Kim, Jin Ho Paik, and Yoon Kyung Jeon. 2020. "Immunophenotypic Landscape and Prognosis of Diffuse Large B-Cell Lymphoma with MYC/BCL2 Double Expression: An Analysis of A Prospectively Immunoprofiled Cohort" Cancers 12, no. 11: 3305. https://doi.org/10.3390/cancers12113305