Original Article

Split Viewer

Blood Res 2020; 55(4):

Published online December 31, 2020

https://doi.org/10.5045/br.2020.2020220

© The Korean Society of Hematology

Long-term treatment outcomes of children and adolescents with lymphoblastic lymphoma treated with various regimens: a single-center analysis

Ho Jung Choi1, Juhee Shin1,2, Sunghan Kang1,2, Jin Kyung Suh1,2, 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

Received: August 29, 2020; Revised: November 2, 2020; Accepted: November 12, 2020

Abstract

Background
Lymphoblastic lymphoma (LBL) is the second most common subtype of pediatric non-Hodgkin lymphoma. Modified treatments derived from the LSA2-L2 regimen resulted in encouraging survival, but toxicities and long-term sequelae have been problematic. At present, the acute lymphoblastic leukemia (ALL)-type protocol has demonstrated efficacy in LBL. We analyzed the outcomes of children and adolescents with LBL treated with various regimens.
Methods
From 1991‒2018, this study enrolled 63 patients diagnosed with LBL at Asan Medical Center. Medical records were retrospectively analyzed.
Results
Among 63 patients, most patients (38.1%) presented with stage IV at diagnosis, and two had central nervous system (CNS) involvement. At a median follow-up of 160 months, the 5-year event free survival (EFS), overall survival (OS), and relapse free survival (RFS) were 68.8%, 79.3%, and 71.3%, respectively. Among 61 patients who received chemotherapy, 27 patients (44.3%) received the NY protocol, and 14 (23.0%) received the ALL-type protocol. There was no significant difference in 5-yr OS (85.2%/78.6%), EFS (73.5%/78.6%), and RFS (73.5%/78.6%) between the NY and ALL protocol groups, regardless of immunophenotype. Thirteen patients (21.3%) received prophylactic cranial radiotherapy with no difference in the incidence of CNS relapse based on irradiation.
Conclusion
This study showed no difference in outcome between the NY and ALL-type protocols, regardless of stage or immunophenotype. In addition to improving the effectiveness of treatment, it is necessary to continuously appraise the appropriate chemotherapy regimen, considering toxicities and long-term prognosis, for pediatric LBL.

Keywords Lymphoblastic lymphoma, Child, Survival, Chemotherapy, New York protocol

Article

Original Article

Blood Res 2020; 55(4): 262-274

Published online December 31, 2020 https://doi.org/10.5045/br.2020.2020220

Copyright © The Korean Society of Hematology.

Long-term treatment outcomes of children and adolescents with lymphoblastic lymphoma treated with various regimens: a single-center analysis

Ho Jung Choi1, Juhee Shin1,2, Sunghan Kang1,2, Jin Kyung Suh1,2, 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

Received: August 29, 2020; Revised: November 2, 2020; Accepted: November 12, 2020

Abstract

Background
Lymphoblastic lymphoma (LBL) is the second most common subtype of pediatric non-Hodgkin lymphoma. Modified treatments derived from the LSA2-L2 regimen resulted in encouraging survival, but toxicities and long-term sequelae have been problematic. At present, the acute lymphoblastic leukemia (ALL)-type protocol has demonstrated efficacy in LBL. We analyzed the outcomes of children and adolescents with LBL treated with various regimens.
Methods
From 1991‒2018, this study enrolled 63 patients diagnosed with LBL at Asan Medical Center. Medical records were retrospectively analyzed.
Results
Among 63 patients, most patients (38.1%) presented with stage IV at diagnosis, and two had central nervous system (CNS) involvement. At a median follow-up of 160 months, the 5-year event free survival (EFS), overall survival (OS), and relapse free survival (RFS) were 68.8%, 79.3%, and 71.3%, respectively. Among 61 patients who received chemotherapy, 27 patients (44.3%) received the NY protocol, and 14 (23.0%) received the ALL-type protocol. There was no significant difference in 5-yr OS (85.2%/78.6%), EFS (73.5%/78.6%), and RFS (73.5%/78.6%) between the NY and ALL protocol groups, regardless of immunophenotype. Thirteen patients (21.3%) received prophylactic cranial radiotherapy with no difference in the incidence of CNS relapse based on irradiation.
Conclusion
This study showed no difference in outcome between the NY and ALL-type protocols, regardless of stage or immunophenotype. In addition to improving the effectiveness of treatment, it is necessary to continuously appraise the appropriate chemotherapy regimen, considering toxicities and long-term prognosis, for pediatric LBL.

Keywords: Lymphoblastic lymphoma, Child, Survival, Chemotherapy, New York protocol

Fig 1.

Figure 1.Survival outcomes of patients. The overall survival (A), event-free survival (B), and relapse-free survival rates (C) were 79.3±5.1%, 68.8±6.6%, and 71.3±5.7%, respectively.
Blood Research 2020; 55: 262-274https://doi.org/10.5045/br.2020.2020220

Fig 2.

Figure 2.When analyzed according to initial stage, patients with stage III/IV disease show lower survival rates than others. However the overall survival (A), and event-free survival rates (B) were not statistically different.
Blood Research 2020; 55: 262-274https://doi.org/10.5045/br.2020.2020220

Fig 3.

Figure 3.When advanced stage patients were analyzed according to immunophenotype, the overall survival (A) and event-free survival rates (B) were not statistically different between B- and T-LBL (N=43).
Blood Research 2020; 55: 262-274https://doi.org/10.5045/br.2020.2020220

Fig 4.

Figure 4.There were 18 events, and 13 patients died. All patients alive to date are disease-free.
Blood Research 2020; 55: 262-274https://doi.org/10.5045/br.2020.2020220

Fig 5.

Figure 5.Treatment outcome according to initial chemotherapy protocol. The overall survival (A), event-free survival (B), and relapse-free survival rates (C) were not statistically different between patients who received the ALL-type and NY regimens (N=41).
Blood Research 2020; 55: 262-274https://doi.org/10.5045/br.2020.2020220

Table 1 . Characteristics of patients..

Characteristics N (%)
Sex
Male34 (54.0%)
Female29 (46.0%)
Median age at diagnosis (range, yr)8 (2–19)
Immunophenotype
T-LBL39 (61.9%)
B-LBL21 (33.3%)
Unknown3 (4.8%)
Mediastinal mass29 (46.0%)
Median LDH level (IU/L)962 (447–3,297)
Stagea)
I8 (12.7%)
II10 (15.9%)
III21 (33.3%)
IV24 (38.1%)
Initial CNS involvement
Involved (+)2 (3.2%)
Involved (-)59 (93.7%)
Unknown2 (3.2%)
Initial BM involvement
Involved (+)21 (33.3%)
Involved (-)42 (66.7%)

a)Murphy and St Jude Children’s Research Hospital Staging system..

Abbreviations: BM, bone marrow; CNS, central nervous system; LBL, lymphoblastic lymphoma; LDH, lactate dehydrogenase..


Table 2 . Number of patients according to chemotherapy protocol..

StageAD-COMPALL-type regimena)LSA2-L2b)NYregimenPOG regimenc)

N
B-LBLI13021
II01012
III00011
IV12131
Total26175
T-LBLII01041
III25380
IV12271
Total385192
UnknownI10000
III00010
IV00100
Total6 (9.8%)14 (23.0%)7 (11.5%)27 (44.3%)7 (11.5%)

a)CCG-1882 or Korean multicenter high-risk ALL protocol; b)CCG-106B, CCG-1901, or CCG-5941; c)POG 9219, POG-9317, POG-9404, or POG-9406. There was no statistically significant difference in age, sex, immunophenotypes, stages, initial CNS or BM involvement between patients of the NY protocol group, and those in the ALL-type protocol group..

Abbreviations: AD-COMP, addition of daunorubicin and asparaginase to the basic COMP protocol; ALL, acute lymphoblastic leukemia; LBL, lymphoblastic lymphoma; NY, New York; POG, Pediatric Oncology Group..


Table 3 . Patients who received stem cell transplantation..

Patient 1Patient 2Patient 3
Age at diagnosis (yr)/sex14/F7/M8/M
ImmunophenotypeB-cellT-cellT-cell
StageIIIIIIV
CNS involvementNoneNoneNone
Initial ChemotherapyPOG-9404COG-1901COG-1901
Reason of transplantationRelapse (mediastinum, kidney)Relapse (mediastinum)Initial extensive stage (BM, mediastinum), poor response
Treatment after relapsePOG-9406, mediastinal radiotherapyICE protocol-
Type of transplantationAutologous PBSCTAutologous PBSCTMatched sibling donor PBSCT
Conditioning regimenTBI/Cy/VP16Bu/Cy/VP16TBI/Cy/rATG
Local radiotherapyMediastinum (post-PBSCT)PCRT mediastinum (post-PBSCT)-
Current statusDeath due to relapsed disease (post-PBSCT 4 mo)Alive without disease (1 yr 5 mo)Alive without disease (7 mo)

Abbreviations: BM, bone marrow; CNS, central nervous system; COG, children’s oncology group; Cy, cyclophosphamide; ICE, ifosfamide, carboplatin, etoposide; PBSCT, peripheral blood stem cell transplantation; PCRT, prophylactic cranial radiotherapy; POG, Pediatric Oncology Group; rATG, rabbit anti-thymocyte globulin; TBI, total body irradiation; VP16, etoposide..


Blood Res
Volume 59 2024

Supplementary File

Stats or Metrics

Share this article on

  • line

Related articles in BR

Blood Research

pISSN 2287-979X
eISSN 2288-0011
qr-code Download