1Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea
2Deparment of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
3Department of Internal Medicine, Konkuk University Medical Center and School of Medicine, Seoul, Korea
4Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Korea
5Division of Hematology-Oncology, Department of Medicine, Dongsan Medical Center, Keimyung University, Daegu, Korea
6Division of Hematology/Oncology, Department of Internal Medicine, Korea University School of Medicine, Seoul, Korea
7Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
8Division of Hematology-Oncology, Department of Internal Medicine, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea
9Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
10Division of Hematology and Oncology, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
11Division of Oncology and Hematology, Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
12Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea
13Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea
14Division of Hematology/Oncology, Department of Internal Medicine, Jeonbuk National University Medical School, Jeonju, Korea
15Division of Hematology-Oncology, Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Science, Seoul, Korea
16Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
Copyright © 2023 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 complied with the principles of the Declaration of Helsinki and guidelines of good clinical practice. The institutional review board or ethics committee at each participating center approved the study protocol and its amendments. Written informed consent was obtained from all the patients.
Author Contributions
Conceived and designed the analysis: Kim KH, Won JH.
Collected the data: Kim KH, Lee JH, Lee M, Kim HG, Do YR, Park Y, Shin HJ, Kim WS, Park SK, Kong JH, Park MR, Yang DH, Kwak JY, Kang HJ, Mun YC, Won JH.
Contributed data or analysis tools: Kim KH, Lee JH, Lee M, Kim HG, Do YR, Park Y, Oh SY, Shin HJ, Kim WS, Park SK, Kong JH, Park MR, Yang DH, Kwak JY, Kang HJ, Mun YC, Won JH.
Performed the analysis: Kim KH, Won JH.
Wrote the paper: Kim KH, Won JH.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Values are presented as number (%) unless otherwise indicated. ALK, anaplastic lymphoma kinase; ASCT, autologous stem cell transplantation; BM, bone marrow; BuCE, busulfan, cyclophosphamide, and etoposide; BuME, busulfan, melphalan, and etopodise; CR, complete response; ECOG, Estern Cooperative Oncology Group; IPI, international prognostic index; NK, natural killer.
Demographic, disease and transplantation characteristics of patients according to conditioning chemotherapy
BuME (n=36) | BuCE (n=39) | p-value | |
---|---|---|---|
Age, median (range, yr) | 51 (18–64) | 55 (30–62) | 0.163 |
> 60 yr of age at ASCT | 5 (13.9) | 4 (10.3) | 0.730 |
Sex | |||
Male | 23 (63.9) | 28 (71.8) | 0.621 |
Female | 13 (36.1) | 11(28.2) | |
Histologic subtype | |||
B-cell lymphoma | 24 (66.7) | 26 (66.7) | > 0.99 |
Diffuse large B-cell lymphoma | 21 (58.3) | 25 (64.1) | |
Mantle cell lymphoma | 3 (8.3) | 1 (2.6) | |
T-cell lymphoma | 12 (33.3) | 13 (33.3) | |
Peripheral T-cell lymphoma, unspecified | 0 | 6 (15.4) | |
Extranodal NK/T-cell lymphoma, nasal type | 4 (11.1) | 2 (5.1) | |
Angioimmunoblastic T-cell lymphoma | 5 (13.9) | 1 (2.6) | |
Enteropathy-associated T-cell lymphoma | 1 (2.8) | 0 | |
Anaplastic large cell lymphoma (ALK–) | 2 (5.6) | 4 (10.3) | |
Ann Arbor stage at diagnosis | |||
1 | 2 (5.6) | 5 (12.8) | 0.568 |
2 | 6 (16.7) | 5 (12.8) | |
3 | 13 (36.1) | 10 (25.6) | |
4 | 15 (41.7) | 19 (48.7) | |
B symptoms at diagnosis | 3 (8.3) | 5 (12.8) | 0.713 |
IPI at diagnosis | |||
Low/low-intermediate (0–2) | 20 (55.6) | 17 (43.6) | 0.359 |
High-intermediate/high (3–5) | 16 (44.4) | 22 (56.4) | |
BM involvement at diagnosis | 4 (11.1) | 5 (12.8) | > 0.99 |
Bulky disease at diagnosis | 0 | 2 (5.1) | 0.494 |
Extranodal involvement at diagnosis | 14 (38.9) | 16 (41.0) | > 0.99 |
Time from diagnosis to ASCT, median (range, mo) | 7.25 (3.5–146.8) | 7.0 (4.3–114.7) | 0.758 |
Performance state at transplantation (ECOG) | |||
0 | 15 (41.7) | 14 (35.9) | 0.332 |
1 | 21(58.3) | 22 (56.4) | |
2 | 0 | 3 (7.7) | |
State of transplantation | |||
High risk in remission (upfront ASCT) | 25 (69.4) | 26 (66.7) | 0.506 |
Refractory to induction treatment | 7 (19.4) | 5 (12.8) | |
Chemosensitive relapse | 4 (11.1) | 8 (20.5) | |
No. of prior chemotherapy regimens | |||
1 | 26 (72.2) | 30 (76.9) | 0.890 |
2 | 9 (25.0) | 8 (20.5) | |
≥3 | 1 (2.8) | 1 (2.6) | |
Response state at transplantation | |||
CR | 26 (72.2) | 31 (79.5) | 0.590 |
No CR | 10 (27.8) | 8 (20.5) | |
Transplanted cell dose | |||
CD34+ cell (×106/kg), mean (range) | 6.38 (2.02–45.07) | 9.14 (2.0–31.5) | 0.485 |
Values are presented as number (%) unless otherwise indicated. ALK, anaplastic lymphoma kinase; ASCT, autologous stem cell transplantation; BM, bone marrow; BuCE, busulfan, cyclophosphamide, and etoposide; BuME, busulfan, melphalan, and etopodise; CR, complete response; ECOG, Estern Cooperative Oncology Group; IPI, international prognostic index; NK, natural killer.
Toxicities according to conditioning chemotherapy (n=75)
Any adverse event | All grade | BuME (n=36) | BuCE (n=39) | p-value (Gr3-Gr4) | |||
---|---|---|---|---|---|---|---|
|
|
|
|||||
BuME (n=36) | BuCE (n=39) | Gr1–Gr2 | Gr3–Gr4 | Gr1–Gr2 | Gr3–Gr4 | ||
Toxicities | |||||||
|
|||||||
Fever | 26 (72.2) | 31 (79.5) | - | - | - | - | 0.590 |
|
|||||||
Fever with documented organism | 7 (19.4) | 6 (15.4) | - | - | - | - | 0.763 |
|
|||||||
Mucositis | 22 (61.1) | 22 (56.4) | 20 (55.5) | 2 (5.6) | 20 (51.2) | 2 (5.1) | > 0.99 |
|
|||||||
Nausea/Vomiting | 26 (72.2) | 26 (66.6) | 23 (63.9) | 3 (8.3) | 19 (48.7) | 7 (17.9) | 0.313 |
|
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Diarrhea | 18 (50.1) | 23 (59.0) | 16 (44.5) | 2 (5.6) | 22 (56.4) | 1 (2.6) | 0.605 |
|
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Hepatic toxicities | 4 (11.2) | 3 (7.8) | 2 (5.6) | 2 (5.6) | 1 (2.6) | 2 (5.2) | > 0.99 |
|
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Skin | 2 (5.6) | 1 (2.6) | 2 (5.6) | 0 | 1 (2.6) | 0 | - |
|
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Bladder | 0 | 1 (2.6) | 0 | 0 | 1 (2.6) | 0 | > 0.99 |
|
|||||||
Pulmonary | 6 (16.7) | 7 (18.0) | 4 (11.1) | 2 (5.6) | 6 (15.4) | 1 (2.6) | 0.605 |
|
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Renal toxicity | 1 (2.8) | 3 (7.7) | 1 (2.8) | 0 | 3 (7.7) | 0 | > 0.99 |
|
|||||||
Peripheral neuropathy | 1 (2.8) | 2 (5.2) | 1 (2.8) | 0 | 2 (5.2) | 0 | - |
|
|||||||
Veno-occlusive disease | 0 | 3 (7.7) | 0 | 0 | 3 (7.7) | 0 | - |
|
|||||||
Cardiac toxicity | 3 (8.4) | 0 | 3 (8.4) | 0 | 0 | 0 | - |
|
|||||||
Death | |||||||
|
|||||||
Non-relapsed death | 1 (2.8) | 1 (2.6) | - | - | - | - |
Values are presented as number (%). BuCE, busulfan, cyclophosphamide, and etoposide; BuME, busulfan, melphalan, and etopodise; Gr, grade.
Risk factor analysis of progression-free survival
Variable | No. of patients | PFS rate at 2 yr (%) | Univariate analysis | Multivariate analysis | ||
---|---|---|---|---|---|---|
|
|
|||||
p-value | HR (95% CI) | p-value | HR (95% CI) | |||
Conditioning regimen | ||||||
|
||||||
BuME | 36 | 65.4 (47.1–78.7) | 0.746 | 0.885 (0.41–1.86) | 0.768 | 0.893 (0.420–1.897) |
|
||||||
BuCE | 39 | 60.0 (42.7–73.7) | 1.000 | 1.000 | ||
|
||||||
Sex | ||||||
|
||||||
Male | 51 | 52.8 (37.9–67.7) | 0.023 | 3.411 (1.181–9.853) | 0.006 | 2.813 (0.952–8.307) |
|
||||||
Female | 24 | 83.1 (61.0–93.3) | 1.000 | 1.000 | ||
|
||||||
No. of prior chemotherapies | ||||||
|
||||||
1 | 56 | 69.1 (55.0–79.5) | 0.018 | 1.000 | 0.012 | 1.000 |
|
||||||
≥2 | 19 | 40.6 (17.6–62.7) | 2.000 (2.573–1.175) | 1.875 (0.796–4.420) | ||
|
||||||
Response state at transplantation | ||||||
|
||||||
CR | 57 | 68.1 (54.2–78.6) | 0.071 | 1.000 | 0.512 | 1.000 |
|
||||||
No CR | 18 | 41.3 (16.8–64.5) | 2.087 (0.938–4.642) | 1.341 (0.558–3.220) | ||
|
||||||
Histologic subtype | ||||||
|
||||||
B cell | 50 | 60.5 (45.3–72.7) | 0.537 | |||
|
||||||
T cell | 25 | 66.2 (43.4–81.6) | ||||
|
||||||
IPI at diagnosis | ||||||
|
||||||
Low/low-intermediate | 37 | 63.4 (45.3–76.9) | 0.926 | |||
|
||||||
High-intermediate/high | 38 | 62.8 (44.1–75.3) | ||||
|
||||||
BM involvement at diagnosis | ||||||
|
||||||
No | 67 | 65.2 (52.1–75.6) | 0.259 | |||
|
||||||
Yes | 8 | 44.4 (13.6–71.9) | ||||
|
||||||
Extranodal involvement | ||||||
at diagnosis | ||||||
|
||||||
No | 45 | 66.2 (50.2–78.0) | 0.444 | |||
|
||||||
Yes | 30 | 56.8 (36.3–72.9) |
BM, bone marrow; BuCE, busulfan, cyclophosphamide, and etoposide; BuME, busulfan, melphalan, and etopodise; CI, confidence interval; CR, complete response; HR, hazard ratio; IPI, international prognostic index; PFS, progression-free survival.
Values are presented as number (%) unless otherwise indicated. ALK, anaplastic lymphoma kinase; ASCT, autologous stem cell transplantation; BM, bone marrow; BuCE, busulfan, cyclophosphamide, and etoposide; BuME, busulfan, melphalan, and etopodise; CR, complete response; ECOG, Estern Cooperative Oncology Group; IPI, international prognostic index; NK, natural killer.
Values are presented as number (%). BuCE, busulfan, cyclophosphamide, and etoposide; BuME, busulfan, melphalan, and etopodise; Gr, grade.
BM, bone marrow; BuCE, busulfan, cyclophosphamide, and etoposide; BuME, busulfan, melphalan, and etopodise; CI, confidence interval; CR, complete response; HR, hazard ratio; IPI, international prognostic index; PFS, progression-free survival.