Original Article

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Blood Res 2022; 57(1):

Published online March 31, 2022

https://doi.org/10.5045/br.2021.2021164

© The Korean Society of Hematology

Clinical characteristics and treatment outcomes of children and adolescents with aggressive mature B-cell lymphoma: a single-center analysis

Woojung Jeon1, Young Kwon Koh1,2, Sunghan Kang1,2, Hyery Kim1,2, Kyung-Nam Koh1,2, Ho Joon Im1,2

1Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, 2Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

Correspondence to : Hyery Kim, M.D., Ph.D.
Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, 88-1 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
E-mail: taban@hanmail.net
*This study was supported by a National Research Foundation of Korea grant, funded by the Korean government(Ministry of Science and ICT) (no. NRF-2018R1C1B5047092).

Received: September 2, 2021; Revised: December 8, 2021; Accepted: December 24, 2021

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.

Abstract

Background
Aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is the most common non-Hodgkin lymphoma in children. The outcome of chemotherapy for B-NHL has improved over decades.
Methods
We reviewed 82 children and adolescents with B-NHL diagnosed at Asan Medical Center between 1993 and 2020. The D-COMP/COMP (daunomycin–cyclophosphamide, doxorubicin, vincristine, and prednisolone), Pediatric Oncology Group (POG)-9219/9315/9317, R-CHOP/CHOP (rituximab–cyclophosphamide, doxorubicin, vincristine, and prednisolone), and Lymphomes Malins B 89 (LMB89)/LMB96 regimens were administered. In 2018, rituximab was added to the LMB protocol (R-LMB) for advanced-staged Burkitt lymphoma (BL). The patients’ clinical features and treatment outcomes were retrospectively analyzed.
Results
The most common subtype was BL (61%), followed by diffuse large B-cell lymphoma (DLBCL) (35%). The median age was 7.8 (range, 1.3‒16.4) years, and the most frequently used regimen was French‒American‒British (FAB)/LMB96 (58 patients, 70.7%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 92.5% and 85.7%, respectively. The EFS rates of patients with BL and DLBCL were 90.0% and 79.3%, respectively. Among the FAB/LMB risk groups, group C (85.7%) had a significantly lower 5-year OS (P =0.037). Eleven events occurred (6 relapses, 3 deaths, and 2 secondary malignancies) during the median follow-up of 7.1 (range, 3.7‒118.5) months. Two patients treated with R-LMB had good outcomes without complications.
Conclusion
Various treatment regimens have favorable outcomes in pediatric patients with B-NHL. However, further studies are needed to improve survival in high-risk patients. In addition, careful monitoring for acute toxicity or secondary malignancy due to intensive multidrug chemotherapy is required.

Keywords Mature B-cell lymphoma, Children, Survival, LMB protocol, Rituximab

Article

Original Article

Blood Res 2022; 57(1): 41-50

Published online March 31, 2022 https://doi.org/10.5045/br.2021.2021164

Copyright © The Korean Society of Hematology.

Clinical characteristics and treatment outcomes of children and adolescents with aggressive mature B-cell lymphoma: a single-center analysis

Woojung Jeon1, Young Kwon Koh1,2, Sunghan Kang1,2, Hyery Kim1,2, Kyung-Nam Koh1,2, Ho Joon Im1,2

1Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, 2Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea

Correspondence to:Hyery Kim, M.D., Ph.D.
Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Ulsan College of Medicine, Asan Medical Center, 88-1 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
E-mail: taban@hanmail.net
*This study was supported by a National Research Foundation of Korea grant, funded by the Korean government(Ministry of Science and ICT) (no. NRF-2018R1C1B5047092).

Received: September 2, 2021; Revised: December 8, 2021; Accepted: December 24, 2021

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.

Abstract

Background
Aggressive mature B-cell non-Hodgkin lymphoma (B-NHL) is the most common non-Hodgkin lymphoma in children. The outcome of chemotherapy for B-NHL has improved over decades.
Methods
We reviewed 82 children and adolescents with B-NHL diagnosed at Asan Medical Center between 1993 and 2020. The D-COMP/COMP (daunomycin–cyclophosphamide, doxorubicin, vincristine, and prednisolone), Pediatric Oncology Group (POG)-9219/9315/9317, R-CHOP/CHOP (rituximab–cyclophosphamide, doxorubicin, vincristine, and prednisolone), and Lymphomes Malins B 89 (LMB89)/LMB96 regimens were administered. In 2018, rituximab was added to the LMB protocol (R-LMB) for advanced-staged Burkitt lymphoma (BL). The patients’ clinical features and treatment outcomes were retrospectively analyzed.
Results
The most common subtype was BL (61%), followed by diffuse large B-cell lymphoma (DLBCL) (35%). The median age was 7.8 (range, 1.3‒16.4) years, and the most frequently used regimen was French‒American‒British (FAB)/LMB96 (58 patients, 70.7%). The 5-year overall survival (OS) and event-free survival (EFS) rates were 92.5% and 85.7%, respectively. The EFS rates of patients with BL and DLBCL were 90.0% and 79.3%, respectively. Among the FAB/LMB risk groups, group C (85.7%) had a significantly lower 5-year OS (P =0.037). Eleven events occurred (6 relapses, 3 deaths, and 2 secondary malignancies) during the median follow-up of 7.1 (range, 3.7‒118.5) months. Two patients treated with R-LMB had good outcomes without complications.
Conclusion
Various treatment regimens have favorable outcomes in pediatric patients with B-NHL. However, further studies are needed to improve survival in high-risk patients. In addition, careful monitoring for acute toxicity or secondary malignancy due to intensive multidrug chemotherapy is required.

Keywords: Mature B-cell lymphoma, Children, Survival, LMB protocol, Rituximab

Fig 1.

Figure 1.Events and outcomes according to treatment protocol.
Abbreviations: HLH, hemophagocytic lymphohistiocytosis; HSCT, hematopoietic stem cell transplantation; NOS, not otherwise specified; RTx, radiotherapy; t-AML, therapy-related acute myeloid leukemia.
Blood Research 2022; 57: 41-50https://doi.org/10.5045/br.2021.2021164

Fig 2.

Figure 2.Survival outcomes of the 82 patients.
Blood Research 2022; 57: 41-50https://doi.org/10.5045/br.2021.2021164

Fig 3.

Figure 3.Treatment outcomes according to histopathologic subtype: overall survival (A) and event-free survival (B) rates.
Abbreviation: NOS, not otherwise specified.
Blood Research 2022; 57: 41-50https://doi.org/10.5045/br.2021.2021164

Fig 4.

Figure 4.Overall survival (A) and event-free survival (B) rates of patients with Burkitt lymphoma and diffuse large B-cell lymphoma according to initial stage.
Blood Research 2022; 57: 41-50https://doi.org/10.5045/br.2021.2021164

Fig 5.

Figure 5.Survival outcomes of patients with Burkitt lymphoma and diffuse large B-cell lymphoma treated with the LMB protocols according to risk group classification: overall survival (A) and event-free survival (B) rates.
Blood Research 2022; 57: 41-50https://doi.org/10.5045/br.2021.2021164

Fig 6.

Figure 6.Survival outcomes of patients with Burkitt lymphoma and diffuse large B-cell lymphoma according to the initial chemotherapy: overall survival (A) and event-free survival (B) rates.
Blood Research 2022; 57: 41-50https://doi.org/10.5045/br.2021.2021164

Table 1 . Characteristics of the patients..

CharacteristicsN=82 (%)
Age at diagnosis, median (range, yr)7.8 (1.3–16.4)
Sex
Male65 (79)
Female17 (21)
Primary site
Abdomen43 (52.4)
Head and neck, except skin and nodes17 (20.7)
Peripheral lymph nodes11 (13.4)
Thorax5 (6.1)
Others4 (5)
Central nervous system2 (2.4)
Pathologic subtype
Burkitt lymphoma50 (61.0)
Diffuse large B-cell lymphoma29 (35.4)
High-grade B-cell lymphoma, not otherwise specified3 (3.6)
BM involvement
Yes14 (17)
No68 (83)
CNS involvement
Yes8 (9.8)
No74 (90.2)
Stage
I4 (4.9)
II26 (31.7)
III30 (36.6)
IV22 (26.8)
Chemotherapy protocol and group
LMB89/LMB9668 (82.9)
Group A6 (8.8)
Group B35 (51.5)
Group C27 (39.7)
POG-9219/9315/93179 (11.0)
D-COMP/COMP3 (3.7)
R-CHOP/CHOP2 (2.4)

Abbreviations: BM, bone marrow; CNS, central nervous system..


Table 2 . Characteristics of the events..

Event characteristics
Total events (N of patients)11
Relapse (N)6
Local relapse4
BM relapse1
CNS relapse1
Median time to relapse (range, mo)6.8 (4.3–13.9)
Pathologic subtype
Burkitt lymphoma2 (33.3%)
Diffuse large B-cell lymphoma4 (66.7%)
Stage
II2 (33.3%)
III3 (50.0%)
IV1 (16.7%)
Salvage regimen
CTx only4 (66.7%)
CTx+RTx1 (16.7%)
CTx+RTx+allo-HSCT1 (16.7%)
Death after relapse (N)4
Death of any cause other than relapse (N)3
Progressive disease2
Treatment related1
Median time to death (range, mo)10.5 (3.7–27.1)
Secondary malignancy (N)2
Therapy-related acute myeloid leukemia1
Follicular thyroid carcinoma1

Abbreviations: BM, bone marrow; CNS, central nervous system; CTx, chemotherapy; HSCT, hematopoietic stem cell transplantation; RTx, radiotherapy..


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