1Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Copyright © 2021 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
The study was approved by the Institutional Review Board of Asan Medical Center (2009-0098) with waiver of the informed consent.
Author Contributions
Conceived and designed the analysis: Park CS, Suh C, Huh J, Go H.
Collected the data: Yoon DH, Hwang HS.
Contributed data or analysis tools: Yoon DH, Suh C.
Performed the analysis: Hwang HS, Kim M.
Wrote the paper: Hwang HS.
Conflicts of Interest
Conflicts of interest relevant to this article was not reported.
Score | Conventional IPI | NCCN-IPI | GELTAMO-IPI |
---|---|---|---|
0 | ≤ 60 | ≤ 40 | < 65 |
1 | > 60 | 41–60 | 65–79 |
2 | - | 61–75 | ≥ 80 |
3 | - | > 75 | - |
ABC, activated B-cell-like; ARDI, average relative dose intensity; DLBCL, diffuse large B-cell lymphoma; ECOG, Eastern Cooperative Oncology Group; GCB, germinal center B-cell-like; GELTAMO, Grupo Español de. Linfomas/Trasplante Autólogo de Médula Ósea; IPI, International Prognostic Index; KM, Kaplan-Meier survival analysis; LDH, lactate dehydrogenase; LGBCL, low-grade B-cell lymphoma; NCCN, National Comprehensive Cancer Network; NOS, not otherwise specified; OS, overall survival; PFS, progression-free survival; PS, performance score; R-CHOP, rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone; R-CVP, rituximab with cyclophosphamide, vincristine and prednisone; SD, standard deviation.
Age cutoffs for the conventional IPI, NCCN-IPI, and GELTAMO-IPI
Score | Conventional IPI | NCCN-IPI | GELTAMO-IPI |
---|---|---|---|
0 | ≤ 60 | ≤ 40 | < 65 |
1 | > 60 | 41–60 | 65–79 |
2 | - | 61–75 | ≥ 80 |
3 | - | > 75 | - |
GELTAMO, Grupo Español de. Linfomas/Trasplante Autólogo de Médula Ósea; IPI, International Prognostic Index; NCCN, National Comprehensive Cancer Network.
Clinical characteristics of the enrolled patients
Characteristic | No. (%) (n=608) | KM p-value (OS) | KM p-value (PFS) |
---|---|---|---|
Age, mean±SD (yr) | 53.3±14.1 | - | - |
Age (yr) (conventional IPI) | |||
≤ 60 | 409 (67.3) | 0.030 | 0.025 |
> 60 | 199 (32.7) | ||
Age (yr) (NCCN-IPI) | |||
≤ 40 | 118 (19.4) | < 0.001 | 0.002 |
41–60 | 291 (47.9) | ||
61–75 | 184 (30.3) | ||
> 75 | 15 (2.5) | ||
Age (yr) (GELTAMO-IPI) | |||
< 65 | 455 (74.8) | < 0.001 | < 0.001 |
≥ 65 and < 80 | 147 (24.2) | ||
≥ 80 | 6 (1.0) | ||
Sex | |||
Male | 335 (55.1) | 0.915 | 0.137 |
Female | 273 (44.9) | ||
Pathologic diagnosis | |||
DLBCL-NOS | 559 (91.9) | 0.781 | 0.558 |
Variant of DLBCL | 26 (4.3) | ||
DLBCL arising from LGBCL | 23 (3.8) | ||
ECOG PS >1 | 40 (6.6) | 0.004 | 0.001 |
Ann Arbor stage III–IV | 300 (49.3) | < 0.001 | < 0.001 |
Extranodal involvement > 1 site | 191 (31.4) | < 0.001 | < 0.001 |
Serum LDH elevation | 287 (47.2) | < 0.001 | < 0.001 |
IPI risk group | |||
Low | 308 (50.7) | < 0.001 | < 0.001 |
Low-intermediate | 19 (17.9) | ||
High-intermediate | 121 (19.9) | ||
High | 70 (11.5) | ||
Age-adjusted IPI risk group | |||
Low | 230 (37.8) | < 0.001 | < 0.001 |
Low-intermediate | 164 (27.0) | ||
High-intermediate | 179 (29.4) | ||
High | 35 (5.8) | ||
Presence of B symptoms | 127 (20.9) | < 0.001 | < 0.001 |
Chemotherapy regimen | |||
R-CHOP | 605 (99.5) | 0.040 | 0.153 |
R-CVP | 3 (0.5) | ||
ARDI< 85% | 179 (29.4) | 0.017 | 0.010 |
Hans cell-of-origin | |||
GCB | 133/402 (33.1) | 0.381 | 0.089 |
ABC | 269/402 (66.9) | ||
Complete remission | 540 (88.8) | - | - |
Median follow-up length (mo) | 46 | - | - |
3-Year survival rate | 508 (83.6) | - | - |
ABC, activated B-cell-like; ARDI, average relative dose intensity; DLBCL, diffuse large B-cell lymphoma; ECOG, Eastern Cooperative Oncology Group; GCB, germinal center B-cell-like; GELTAMO, Grupo Español de. Linfomas/Trasplante Autólogo de Médula Ósea; IPI, International Prognostic Index; KM, Kaplan-Meier survival analysis; LDH, lactate dehydrogenase; LGBCL, low-grade B-cell lymphoma; NCCN, National Comprehensive Cancer Network; NOS, not otherwise specified; OS, overall survival; PFS, progression-free survival; PS, performance score; R-CHOP, rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone; R-CVP, rituximab with cyclophosphamide, vincristine and prednisone; SD, standard deviation.
Results of multivariate Cox PH analysis of age variables categorized according to the NCCN-IPI criterion
Parameter | OS | PFS | ||||
---|---|---|---|---|---|---|
|
| |||||
HR | 95% CI | p-value | HR | 95% CI | p-value | |
Age-adjusted IPI risk | ||||||
| ||||||
Low | 1 | - | - | 1 | - | - |
| ||||||
Low-intermediate | 1.44 | 0.77–2.71 | 0.252 | 1.72 | 1.08–2.73 | 0.022 |
| ||||||
High-intermediate | 4.38 | 2.59–7.43 | < 0.001 | 3.37 | 2.21–5.15 | < 0.001 |
| ||||||
High | 3.67 | 1.69–7.97 | 0.001 | 3.36 | 1.78–6.33 | < 0.001 |
| ||||||
ARDI < 85% | 1.07 | 0.72–1.61 | 0.728 | 1.06 | 0.75–1.50 | 0.729 |
| ||||||
Presence of B symptoms | 1.61 | 1.07–2.41 | 0.022 | 1.47 | 1.04–2.09 | 0.031 |
| ||||||
Age (yr) | ||||||
| ||||||
≤ 40 | 1 | - | - | 1 | - | - |
| ||||||
41–60 | 0.76 | 0.46–1.24 | 0.271 | 0.95 | 0.62–1.45 | 0.804 |
| ||||||
61–75 | 1.00 | 0.60–1.69 | 0.989 | 1.19 | 0.75–1.87 | 0.463 |
| ||||||
> 75 | 3.11 | 1.36–7.12 | 0.007 | 2.74 | 1.27–5.92 | 0.010 |
ARDI, average relative dose intensity; CI, confidence interval; HR, hazard ratio; IPI, International Prognostic Index; NCCN, National Comprehensive Cancer Network; OS, overall survival; PFS, progression-free survival; PH, proportional hazard.
Results of multivariate Cox PH analysis of age variables categorized according to the conventional IPI criterion
Parameter | OS | PFS | ||||
---|---|---|---|---|---|---|
|
| |||||
HR | 95% CI | p-value | HR | 95% CI | p-value | |
Age-adjusted IPI risk | ||||||
| ||||||
Low | 1 | - | - | 1 | - | - |
| ||||||
Low-intermediate | 1.44 | 0.77–2.70 | 0.255 | 1.71 | 1.08–2.71 | 0.023 |
| ||||||
High-intermediate | 4.55 | 2.68–7.72 | < 0.001 | 3.44 | 2.25–5.25 | < 0.001 |
| ||||||
High | 3.66 | 1.69–7.94 | 0.001 | 3.33 | 1.77–6.28 | 0.0002 |
| ||||||
ARDI | ||||||
| ||||||
< 85% | 1.10 | 0.74–1.64 | 0.650 | 1.09 | 0.78–1.53 | 0.621 |
| ||||||
Presence of B symptoms | 1.54 | 1.03–2.31 | 0.037 | 1.45 | 1.02–2.06 | 0.040 |
| ||||||
Age (yr) | ||||||
| ||||||
> 60 | 1.36 | 0.92–2.00 | 0.121 | 1.33 | 0.95–1.84 | 0.092 |
ARDI, average relative dose intensity; CI, confidence interval; HR, hazard ratio; IPI, International Prognostic Index; OS, overall survival; PFS, progression-free survival; PH, proportional hazard.
Results of multivariate Cox PH analysis of age variables categorized according to the GELTAMO-IPI criterion
Parameter | OS | PFS | ||||
---|---|---|---|---|---|---|
|
| |||||
HR | 95% CI | p-value | HR | 95% CI | p-value | |
Age-adjusted IPI risk | ||||||
| ||||||
Low | 1 | - | - | 1 | - | - |
| ||||||
Low-int. | 1.42 | 0.76–2.66 | 0.276 | 1.68 | 1.06–2.67 | 0.028 |
| ||||||
High-int. | 4.30 | 2.53–7.32 | < 0.001 | 3.31 | 2.16–5.07 | < 0.001 |
| ||||||
High | 3.65 | 1.68–7.91 | 0.001 | 3.31 | 1.76–6.24 | < 0.001 |
| ||||||
ARDI | ||||||
| ||||||
< 85% | 1.04 | 0.69–1.57 | 0.839 | 1.04 | 0.74–1.47 | 0.811 |
| ||||||
Presence of B symptoms | 1.60 | 1.06–2.41 | 0.024 | 1.48 | 1.04–2.11 | 0.029 |
| ||||||
Age (yr) | ||||||
| ||||||
< 65 | 1 | - | - | 1 | - | - |
| ||||||
65–79 | 1.45 | 0.95–2.21 | 0.082 | 1.45 | 1.02–2.06 | 0.041 |
| ||||||
≥ 80 | 4.14 | 1.47–11.65 | 0.007 | 2.50 | 0.90–6.92 | 0.078 |
ARDI, average relative dose intensity; CI, confidence interval; GELTAMO, Grupo Español de. Linfomas/Trasplante Autólogo de Médula Ósea; HR, hazard ratio; int., intermediate; IPI, international prognostic index; OS, overall survival; PFS, progression-free survival; PH, proportional hazard.
GELTAMO, Grupo Español de. Linfomas/Trasplante Autólogo de Médula Ósea; IPI, International Prognostic Index; NCCN, National Comprehensive Cancer Network.
ABC, activated B-cell-like; ARDI, average relative dose intensity; DLBCL, diffuse large B-cell lymphoma; ECOG, Eastern Cooperative Oncology Group; GCB, germinal center B-cell-like; GELTAMO, Grupo Español de. Linfomas/Trasplante Autólogo de Médula Ósea; IPI, International Prognostic Index; KM, Kaplan-Meier survival analysis; LDH, lactate dehydrogenase; LGBCL, low-grade B-cell lymphoma; NCCN, National Comprehensive Cancer Network; NOS, not otherwise specified; OS, overall survival; PFS, progression-free survival; PS, performance score; R-CHOP, rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone; R-CVP, rituximab with cyclophosphamide, vincristine and prednisone; SD, standard deviation.
ARDI, average relative dose intensity; CI, confidence interval; HR, hazard ratio; IPI, International Prognostic Index; NCCN, National Comprehensive Cancer Network; OS, overall survival; PFS, progression-free survival; PH, proportional hazard.
ARDI, average relative dose intensity; CI, confidence interval; HR, hazard ratio; IPI, International Prognostic Index; OS, overall survival; PFS, progression-free survival; PH, proportional hazard.
ARDI, average relative dose intensity; CI, confidence interval; GELTAMO, Grupo Español de. Linfomas/Trasplante Autólogo de Médula Ósea; HR, hazard ratio; int., intermediate; IPI, international prognostic index; OS, overall survival; PFS, progression-free survival; PH, proportional hazard.