1Department of Hematology-Oncology, Ajou University Hospital, Suwon, Korea
2Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
4Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
5Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
6Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
7Divison of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Korea
8Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
9Department of Internal Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea
10Department of Medicine, Dongsan Medical Center, Daegu, Korea
11Department of Medicine, Yeungnam University College of Medicine, Daegu, Korea
12Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
13Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea
14Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea
15Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
16Hematology-Oncology Clinic, National Cancer Center, Goyang, Korea
17Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Korea
18Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
19Department of Inter- nal Medicine, Hanyang University College of Medicine, Seoul, Korea
20Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
21Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
22Department of Internal Medicine, Chungbuk National University Hospital, Chungju, Korea
23Department of Internal Medicine, Dong-A University Medical Center, Busan, Korea
24Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
25Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul, Korea
26Department of Hematology-Oncology, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
27Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
28Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea
Copyright © 2022 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 protocol was reviewed and approved by the institutional review board of each participating center, and all patients provided written informed consent before treatment initiation; Gachon University Gil Medical Center: GCIRB2015-74, Gyeongsang National University Hospital: GNUH 2015-02-012, Dongsan Medical Center: DSMC 2015-03-015, Korea University Anam Hospital: ED15024(AN15024-001), Kosin University Gospel Hospital: KUGH 2017-09-008, National Cancer Center: NCC 2015-0091, Dong-A University Medical Center: DMC 15-037, Pusan National University Hospital: H-1701-011-051, Samsung Medical Center: SMC 2014-07-181, Seoul National University Hospital: H-1504-119-667, Asan Medical Center: S2015-0302-0001, Soonchunhyang University Hospital: SCHUH 2015-05-007, Soonchunhyang University Bucheon Hospital: SCHBC 2015-07-008, Wonju Severance Christian Hospital: CR315002-002, Ajou University Hospital: AJIRB-MED-OBS-14-254, Yeungnam University Medical Center: YUMC 2015-03-016, Korea Cancer Center Hospital: K-1409-001-001, Ulsan University Hospital: UUH 2015-11-007, Inje University Sanggye Paik Hospital: SGPAIK 2015-06-002, Inje University Ilsan Paik Hospital: ISPAIK 2015-07-002, Inje University Busan Paik Hospital: BS 2015-0110, Jeonbuk National University Hospital: CUH 2015-02-034, Chonnam National University Hwasun Hospital: TMP-2015-023, Chung-Ang University Hospital: C2015048(1506), Chungnam National University Hospital: CNUH 2015-10-060, Chungbuk National University Hospital: CBNUH 2015-03-006, Hallym University Sacred Heart Hospital: HUH 2015-I043.
Author Contributions
Conceived and designed the analysis: Jeong SH, Kim SJ, Kim WS.
Collected the data: Jeong SH, Kim SJ, Yoon DH, Park Y, Kang HJ, Koh Y, Lee GW, Lee WS, Yang DH, Do YR, Kim MK, Yoo KH, Choi YS, Yun HJ, Yi JH, Jo JC, Eom HS, Kwak JY, Shin HJ, Park BB, Hyun SY, Yi SY, Kwon JH, Oh SY, Kim HJ, Sohn BS, Won JH, Kim SH, Lee HS, Suh C, Kim WS.
Contributed data or analysis tools: Jeong SH, Kim SJ, Choi YS, Kim WS.
Performed the analysis: Jeong SH, Kim SJ, Kim WS.
Wrote the paper: Jeong SH, Kim SJ.
Conflicts of Interest
This study was supported by the Kyowa Kirin Korea Co., Ltd.
Characteristic | This cohort | PROCESS cohort | p-value |
---|---|---|---|
Neutropenia (grade 4) | |||
Patients | 286 (29.0) | 335 (69.1) | < 0.001 |
Cycles | 626 (11.7) | 193 (39.8) | < 0.001 |
FN | |||
Patients | 137 (13.9) | 115 (23.7) | < 0.001 |
Cycles | 225 (4.2) | 264 (10.2) | < 0.001 |
TRM | 32 (3.2) | 27 (5.6) | 0.047 |
Infection-related | 18 (1.8) | 22 (4.5) | 0.004 |
Patients age ≥ 75 yr | 5 (3.0) | 8 (11.6) | 0.023 |
Non-infectiousa) | 14 (1.4) | 5 (1.0) | 0.535 |
Values are presented as number (%). FN, febrile neutropenia; TRM, treatment-related mortality within 6 months of the initiation of treatment.
a) TRM of non-infectious causes includes intracranial hemorrhage, cardiac event, pneumothorax, acute exacerbation of chronic pulmonary obstructive disease, hepatic failure and bowel infarction.
Chemotherapy | This cohort | PROCESS cohort | p-value |
---|---|---|---|
Completion of 6 cycles | 765 (77.6) | 355 (73.2) | 0.069 |
Dose delay | |||
> 3 days | 179 (18.2) | 115 (23.7) | 0.015 |
> 5 days | 119 (12.1) | 80 (16.5) | 0.023 |
Dose reduction > 20% | |||
Doxorubicin | 192 (19.5) | 75 (15.5) | 0.062 |
Cyclophosphamide | 131 (13.3) | 73 (15.1) | 0.378 |
ARDI ≥ 80%a) | 722 (73.2) | 344 (70.9) | 0.353 |
Characteristics of patients
Characteristic | This cohort (n=986) | PROCESS cohort (n=485) | p-value |
---|---|---|---|
Age (yr) | |||
Median (range) | 62 (19–86) | 59 (20–89) | |
≥ 65 | 423 (42.9) | 185 (38.1) | 0.090 |
≥ 75 | 166 (16.8) | 69 (14.2) | 0.226 |
Sex | |||
Male | 555 (56.3) | 275 (56.7) | 0.911 |
Female | 431 (43.7) | 210 (43.3) | |
ECOG | |||
0, 1 | 901 (91.4) | 429 (88.6) | 0.108 |
≥ 2 | 85 (8.6) | 55 (11.4) | |
Stage | |||
1, 2 | 478 (48.5) | 239 (49.3) | 0.824 |
3, 4 | 508 (51.5) | 246 (50.7) | |
Extranodal sites | |||
0 or 1 | 620 (62.9) | 314 (64.8) | 0.488 |
≥ 2 | 366 (37.1) | 171 (35.2) | |
BM involvement | |||
No | 877 (88.9) | 429 (88.5) | 0.792 |
Yes | 109 (11.1) | 56 (11.5) | |
LDH elevation | |||
No | 467 (47.4) | 252 (52.0) | 0.096 |
Yes | 519 (52.6) | 233 (48.0) | |
IPI | |||
0 or 1 | 362 (36.7) | 217 (44.7) | 0.075 |
2 | 254 (25.8) | 100 (20.6) | |
3 | 203 (20.6) | 91 (18.8) | |
4 or 5 | 167 (16.9) | 77 (15.9) | |
Albumin (mg/dL) | |||
≥ 3.5 | 738 (74.8) | 370 (76.3) | 0.608 |
< 3.5 | 248 (25.2) | 115 (23.7) |
Values are presented as number (%) unless otherwise indicated. BM, bone marrow; ECOG, Eastern Cooperative Oncology Group; IPI, international prognostic index; LDH, lactate dehydrogenase.
Incidence of neutropenia, FN, and TRM according to pegfilgrastim prophylaxis
Characteristic | This cohort | PROCESS cohort | p-value |
---|---|---|---|
Neutropenia (grade 4) | |||
Patients | 286 (29.0) | 335 (69.1) | < 0.001 |
Cycles | 626 (11.7) | 193 (39.8) | < 0.001 |
FN | |||
Patients | 137 (13.9) | 115 (23.7) | < 0.001 |
Cycles | 225 (4.2) | 264 (10.2) | < 0.001 |
TRM | 32 (3.2) | 27 (5.6) | 0.047 |
Infection-related | 18 (1.8) | 22 (4.5) | 0.004 |
Patients age ≥ 75 yr | 5 (3.0) | 8 (11.6) | 0.023 |
Non-infectious |
14 (1.4) | 5 (1.0) | 0.535 |
Values are presented as number (%). FN, febrile neutropenia; TRM, treatment-related mortality within 6 months of the initiation of treatment.
a)TRM of non-infectious causes includes intracranial hemorrhage, cardiac event, pneumothorax, acute exacerbation of chronic pulmonary obstructive disease, hepatic failure and bowel infarction.
Delivery of R-CHOP according to pegfilgrastim ylaxis
Chemotherapy | This cohort | PROCESS cohort | p-value |
---|---|---|---|
Completion of 6 cycles | 765 (77.6) | 355 (73.2) | 0.069 |
Dose delay | |||
> 3 days | 179 (18.2) | 115 (23.7) | 0.015 |
> 5 days | 119 (12.1) | 80 (16.5) | 0.023 |
Dose reduction > 20% | |||
Doxorubicin | 192 (19.5) | 75 (15.5) | 0.062 |
Cyclophosphamide | 131 (13.3) | 73 (15.1) | 0.378 |
ARDI ≥ 80% |
722 (73.2) | 344 (70.9) | 0.353 |
Values are presented as number (%). ARDI, average relative dose intensity; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone.
a)ARDI was calculated by averaging the delivered. Relative dose intensities of cyclophosphamide and doxorubicin.
Univariate analysis of risk factors for FN according to pegfilgrastim prophylaxis
Characteristic | This cohort | p-value | PROCESS cohort | p-value |
---|---|---|---|---|
Age (yr) | ||||
< 65 | 47 (8.3) | < 0.001 | 38 (12.7) | < 0.001 |
≥ 65 | 90 (21.3) | 77 (41.6) | ||
Sex | ||||
Male | 66 (11.9) | 0.041 | 59 (21.5) | 0.197 |
Female | 71 (16.5) | 56 (26.7) | ||
BM involvement | ||||
No | 124 (13.8) | 0.615 | 100 (23.3) | 0.616 |
Yes | 13 (11.9) | 15 (26.8) | ||
Ann Arbor stage | ||||
I–III | 62 (11.4) | 0.461 | 51 (20.1) | 0.242 |
IV | 75 (17.3) | 64 (27.2) | ||
LDH elevation | ||||
No | 47 (10.1) | 0.003 | 35 (18.6) | 0.036 |
Yes | 90 (17.2) | 80 (26.9) | ||
ECOG PS | ||||
0 or 1 | 110 (12.2) | < 0.001 | 90 (21.0) | < 0.001 |
≥ 2 | 27 (31.8) | 25 (44.6) | ||
Extranodal sites | ||||
0 or 1 | 82 (13.2) | 0.447 | 74 (23.6) | 0.914 |
≥ 2 | 55 (15.0) | 41 (24.0) | ||
Albumin (mg/dL) | ||||
< 3.5 | 64 (25.7) | < 0.001 | 40 (33.6) | 0.004 |
≥ 3.5 | 73 (9.9) | 75 (20.5) | ||
Baseline ANC (/μL) | ||||
< 1,500 | 3 (12.5) | > 0.99 | 4 (28.5) | 0.750 |
≥≥ 1,500 | 134 (13.9) | 111 (23.6) | ||
Baseline Hb (mg/dL) | ||||
< 12 | 58 (13.3) | 0.644 | 55 (26.4) | 0.236 |
≥ 12 | 79 (14.4) | 60 (21.7) |
Values are presented as number (%). ANC, absolute neutrophil count; BM, bone marrow; ECOG PS, Eastern Cooperative Oncology Group performance status; FN, febrile neutropenia; Hb, hemoglobin; LDH, lactate dehydrogenase.
Multivariate analysis of risk factors for FN according to pegfilgrastim prophylaxis
Characteristic | This cohort | PROCESS cohort | ||||
---|---|---|---|---|---|---|
|
| |||||
HR | 95% CI | p-value | HR | 95% CI | p-value | |
Age ≥ 65 yr | 2.550 | 1.757–3.903 | < 0.001 | 4.308 | 2.719–6.826 | < 0.001 |
| ||||||
Female | 1.505 | 1.068–2.316 | 0.037 | - | - | - |
| ||||||
ECOG | 2.376 | 1.380–4.092 | 0.002 | 2.500 | 1.072–5.832 | 0.034 |
| ||||||
LDH | 1.408 | 0.938–2.115 | 0.099 | 1.289 | 0.768–2.162 | 0.336 |
| ||||||
Albumin < 3.5 mg/dL | 2.978 | 2.017–4.396 | < 0.001 | 1.808 | 0.943–3.485 | 0.074 |
CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; FN, febrile neutropenia; HR, hazard ratio; LDH, lactate dehydrogenase.
Values are presented as number (%) unless otherwise indicated. BM, bone marrow; ECOG, Eastern Cooperative Oncology Group; IPI, international prognostic index; LDH, lactate dehydrogenase.
Values are presented as number (%). FN, febrile neutropenia; TRM, treatment-related mortality within 6 months of the initiation of treatment. TRM of non-infectious causes includes intracranial hemorrhage, cardiac event, pneumothorax, acute exacerbation of chronic pulmonary obstructive disease, hepatic failure and bowel infarction.
Values are presented as number (%). ARDI, average relative dose intensity; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. ARDI was calculated by averaging the delivered. Relative dose intensities of cyclophosphamide and doxorubicin.
Values are presented as number (%). ANC, absolute neutrophil count; BM, bone marrow; ECOG PS, Eastern Cooperative Oncology Group performance status; FN, febrile neutropenia; Hb, hemoglobin; LDH, lactate dehydrogenase.
CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; FN, febrile neutropenia; HR, hazard ratio; LDH, lactate dehydrogenase.