Blood Res 2020; 55(4):
Published online December 31, 2020
https://doi.org/10.5045/br.2020.2020220
© The Korean Society of Hematology
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
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
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.
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
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
Table 1 . Characteristics of patients..
Characteristics | N (%) |
---|---|
Sex | |
Male | 34 (54.0%) |
Female | 29 (46.0%) |
Median age at diagnosis (range, yr) | 8 (2–19) |
Immunophenotype | |
T-LBL | 39 (61.9%) |
B-LBL | 21 (33.3%) |
Unknown | 3 (4.8%) |
Mediastinal mass | 29 (46.0%) |
Median LDH level (IU/L) | 962 (447–3,297) |
Stagea) | |
I | 8 (12.7%) |
II | 10 (15.9%) |
III | 21 (33.3%) |
IV | 24 (38.1%) |
Initial CNS involvement | |
Involved (+) | 2 (3.2%) |
Involved (-) | 59 (93.7%) |
Unknown | 2 (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..
Stage | AD-COMP | ALL-type regimena) | LSA2-L2b) | NY | POG regimenc) | |
---|---|---|---|---|---|---|
N | ||||||
B-LBL | I | 1 | 3 | 0 | 2 | 1 |
II | 0 | 1 | 0 | 1 | 2 | |
III | 0 | 0 | 0 | 1 | 1 | |
IV | 1 | 2 | 1 | 3 | 1 | |
Total | 2 | 6 | 1 | 7 | 5 | |
T-LBL | II | 0 | 1 | 0 | 4 | 1 |
III | 2 | 5 | 3 | 8 | 0 | |
IV | 1 | 2 | 2 | 7 | 1 | |
Total | 3 | 8 | 5 | 19 | 2 | |
Unknown | I | 1 | 0 | 0 | 0 | 0 |
III | 0 | 0 | 0 | 1 | 0 | |
IV | 0 | 0 | 1 | 0 | 0 | |
Total | 6 (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 1 | Patient 2 | Patient 3 | |
---|---|---|---|
Age at diagnosis (yr)/sex | 14/F | 7/M | 8/M |
Immunophenotype | B-cell | T-cell | T-cell |
Stage | III | II | IV |
CNS involvement | None | None | None |
Initial Chemotherapy | POG-9404 | COG-1901 | COG-1901 |
Reason of transplantation | Relapse (mediastinum, kidney) | Relapse (mediastinum) | Initial extensive stage (BM, mediastinum), poor response |
Treatment after relapse | POG-9406, mediastinal radiotherapy | ICE protocol | - |
Type of transplantation | Autologous PBSCT | Autologous PBSCT | Matched sibling donor PBSCT |
Conditioning regimen | TBI/Cy/VP16 | Bu/Cy/VP16 | TBI/Cy/rATG |
Local radiotherapy | Mediastinum (post-PBSCT) | PCRT mediastinum (post-PBSCT) | - |
Current status | Death 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..
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