Clinical Features and Therapeutic Evaluation of Central Nervous System Involvement in Pediatric Anaplastic Large Cell Lymphoma

Yang, Xiaomei

Oral and Poster Abstracts
624. Hodgkin Lymphomas and T/NK Cell Lymphomas: Clinical and Epidemiological: Poster I

Clinical Practice (Health Services and Quality), Lymphomas, T Cell lymphoma, Diseases, Lymphoid Malignancies

Xiaomei Yang¹^*, Jing Yang²^*, Shuang Huang²^*, Yanlong Duan²^*, Ling Jin²^*, Fu Li¹^*, Lian Du¹^*, Mincui Zheng³^*, Pan Wu³^*, Ying Liu⁴^*, Bo Hu⁴^*, Yunpeng Dai⁵^*, Guotao Guan⁵^*, Ansheng Liu⁶^*, Shuang Qin⁶^*, Lirong Sun⁷^*, Jian Jiang⁸^*, Wei Liu, MD⁹^*, Jianwen Zhou⁹^*, Jian Wang¹⁰^*, Lijun Qu¹⁰^*, Leping Zhang¹¹^*, Yueping Jia¹¹^*, Xiaojun Yuan¹²^*, Yushuang Dong¹²^*, Baoxi Zhang¹³^*, Lian Jiang¹⁴^*, ZhuJun Wang¹⁵^*, XiGe Wang¹⁶^*, Shuquan Zhuang¹⁷^*, Chunju Zhou¹⁸^*, Zifen Gao¹⁹^* and Yonghong Zhang⁴^*

¹Department of Pediatric Hematology/Oncology, Shandong University Affiliated Hospital (Jinan Children's Hospital), Jinan, China
²Department of Pediatric Oncology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
³Department of Hematology, Hunan Children's Hospital, Changsha, China
⁴Department of Pediatric Lymphoma, Beijing Gobroad Boren Hospital, Beijing, China
⁵Department of Pediatrics Hematology and Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
⁶Department of Hematologic Oncology, Xi'an Children's Hospital, Xi'an, China
⁷Department of Pediatric Hematology and Oncology, Affiliated Hospital of Qingdao University, Qingdao, China
⁸Department of Pediatric Hematology and Oncology ，Affiliated Hospital of Qingdao University, Qingdao, China
⁹Department of Hematology & Oncology, Zhengzhou Children's Hospital, Zhengzhou, China
¹⁰Department of Hematology and Oncology, Anhui Provincial Children’s Hospital, Hefei, China
¹¹Department of Pediatrics, Peking University People's Hospital, Beijing, China
¹²Department of Pediatric Hematology and Oncology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
¹³Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, China
¹⁴Department of Pediatrics, The fourth Hospital of Hebei Medical University, Shijiazhuang, China
¹⁵Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
¹⁶Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
¹⁷Department of Pediatric,Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China
¹⁸Department of Pathology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
¹⁹Department of Pathology, Peking University Third Hospital, Beijing, Beijing, China

Objective：To analyze the clinical features of central nervous system involvement (CNS3) in pediatric anaplastic large cell lymphoma (ALCL) and evaluate the efficacy of CNCL-ALCL-2017 protocol for the treatment of CNS3.

Methods：The clinical data of 215 pediatric ALCL patients ≤18 years old enrolled in the Chinese Children's Cancer Group (CNCL) between April 2017 and March 2023 were collected sequentially. All enrolled patients staging and CNS layering were according to the IPNHLSS staging system and treated with CNCL-ALCL-2017 protocol (modified BFM-ALCL99 protocol). The clinical features at diagnosis and treatment outcomes of CNS3 patients were analyzed. All patients were followed up until June 30, 2023. Data were collected using a unified information platform. Associations between patient characteristics were analyzed with Chi-squared or Fisher’s exact tests. Eventfree survival (EFS) and overall survival (OS) curves were estimated according to the KaplanMeier method and compared by Logrank test. Furthermore, statistical analysis was performed using SPSS 22.0 software. P<0.05 was considered statistically significant.

Results: Among the 215 ALCL pediatric patients, 17 (7.9%) had CNS3, including 13 males and 4 females with median age of 8.0 (range 1.0-14.0) years. In this patients, brain parenchyma and spinal cord involvement were found in 58.8% (10/17) patients on imaging, with space-occupying lesions in 7 cases and abnormal signals on MRI in 4 cases. Concurrent space-occupying lesions and abnormal signals on MRI was detected in 1 case. Cerebrospinal fluid (CSF) positivity was detected in 35.3% (6/17) patients, including 2 cases with positive ALK gene and 5 cases with positive flow cytometry, with 1 case positive for both. Cranial nerve deficits such as facial nerve palsy, visual or hearing impairment were observed in 23.5% (4/17) patients. Concurrent CSF, imaging and cranial nerve abnormalities were present in 5.9% (1/17), while two of this were present in 29.4% (5/17). Isolated CSF positivity without other abnormalities was detected in 23.5% (4/17). Pathological subtypes included common type (76.5%, 13/17), histiocyte-rich variant (5.9%, 1/17), small cell variant (5.9%, 1/17), others (11.8%, 2/17). Immunohistochemistry showed ALK⁺ in 94.1% (16/17) and CD3⁺ in 76.5% (13/17). Concurrent ALK gene positivity in both peripheral blood and bone marrow was detected in 64.7% (11/17), with 58.8% (10/17) positive in both samples. The median follow-up of all patients was 35.4 months (range 0.5-74.9). All CNS3 patients had stage IV disease and were treated with regimen D (with 5 g/m² methotrexate). The 3-year OS was 94.3%, 98.2% and 93.3% for CNS1 (144, 67.0%), CNS2 (54, 25.1%) and CNS3 (17, 7.9%) patients, respectively; the 3-year EFS was 85.6%, 90.3% and 86.7%, respectively. No significant differences were found among the three groups. The 3-year OS and EFS for the whole cohort were 95.1% and 84.7%, respectively, also with no significant differences from the CNS3 group. Of the CNS3 patients, 1 was lost to follow-up after the first course, 1 died during treatment, and the interim CR rate was 75.0% (12/16). CSF conversion was achieved in 3/6 (50%) CSF-positive patients. 6.25% (1/16) patient had CSF ALK gene re-positivity during maintenance and persistent positivity despite additional ALK inhibitor alectinib and intrathecal therapy. In the CNS1 group, 2 cases were lost to follow-up and 4 cases died. The relapse rate was 11.4% (16/140), and the rate of central nervous system relapse was 2.1% (3/140). Additionally, the rate of CNS1 relapse was slightly higher but not statistically significantly different for CNS2.

Conclusions: CNS involvement is relatively rare in pediatric ALCL. Detection rate of CNS3 can be improved by CSF flow cytometry and gene screening. The prognosis of CNS3 was significantly improved with CNCL-ALCL-2017 protocol, which may be related to the increased dose of methotrexate in the protocol. The short follow-up time and the small number of cases in this group may affect the results. Furthermore, CNS relapse rate of CNS2 was not markedly higher compared to CNS1.

Keywords: Anaplastic large cell lymphoma; Pediatric; Central nervous system; Clinical features; Prognosis

Disclosures: No relevant conflicts of interest to declare.

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1709 Clinical Features and Therapeutic Evaluation of Central Nervous System Involvement in Pediatric Anaplastic Large Cell Lymphoma