CCCG-ALCL-2020 for Chinese Children and Adolescents With Newly Diagnosed High-risk ALCL

Using a Modified ALCL99 Regimen for Chinese Children With Newly Diagnosed High-risk Anapestic Large Cell Lymphoma

Shanghai Children's Medical Center, Nanjing Children's Hospital, Qilu Hospital of Shandong University, Tianjin Cancer Hospital, West China Second University Hospital, Xiangya Hospital, 1st Affiliated Hospital of Zhengzhou University, Shenzhen Children's Hospital, Sun Yat-Sen Memorial Hospital Zhongshan University

A prospective study on the efficacy of modified ALCL99 regimens in the treatment of the current Chinese pediatric and adolescent high-risk ALCL and compared with our historical data.

Anaplastic large cell lymphoma (ALCL) accounts for 15% of pediatric and adolescent non-Hodgkin lymphomas (NHLs). In our historical study (retrospective multicenter study), the 3-year event-free survival (EFS) was 65% for 80 eligible patients treated in 10 centers between January 2009 and June 2014. The ALCL99 trial reported a 2-year overall survival of 92% and 2-year event-free survival of 74% then become the current standard frontline treatment for pediatric ALCL. The recent long-term follow-up data from ALCL99 trial highlighted its excellent outcome. A less toxic schedule of methotrexate (MTX) 3g/m2 in a 3-hour infusion without intrathecal therapy reproduced the favorable results from previous reports of NHL-BFM90 protocol with MTX at 1g/m2 in a 3-hour infusion. Additionally, a prospective ALCL-Relapse trial by the European Inter-Group for Childhood Non-Hodgkin Lymphoma demonstrated 80% of patients with a late relapse can be cured by 24 months of vinblastine monotherapy. However, vinblastine would not be advised as a treatment option in mainland China due to its inaccessibility. A pilot experience using single-drug vinorelbine in 4 pediatric patients with relapsed ALCL with satisfactory outcome provides the rational for studying vinorelbine as a front line drug option.

Dexamethasone 5 mg/m2 Days 1 and 2; 10mg/m2 Day 3 to 5; Cyclophosphamide 200 mg/m2 Days 1 and 2 Intrathecal therapy Day 1

vinorelbine 25 mg/m2, Day 1 Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Etoposide 100mg/m2, Days 4 to 5; Ifosfamide 800 mg/m2, Days 1 to 5; Cytarabine 150 mg/m2, q12h Days 4 to 5;

vinorelbine 25 mg/m2, Day 1; Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Cyclophosphamide 200 mg/m2, Days 1 to 5; Doxorubicin 25 mg/m2, Days 4 to 5;

vinorelbine 25 mg/m2, Day 1 Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Etoposide 100mg/m2, Days 4 to 5; Ifosfamide 800 mg/m2, Days 1 to 5; Cytarabine 150 mg/m2, q12h Days 4 to 5;

vinorelbine 25 mg/m2, Day 1; Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Cyclophosphamide 200 mg/m2, Days 1 to 5; Doxorubicin 25 mg/m2, Days 4 to 5;

vinorelbine 25 mg/m2, Day 1 Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Etoposide 100mg/m2, Days 4 to 5; Ifosfamide 800 mg/m2, Days 1 to 5; Cytarabine 150 mg/m2, q12h Days 4 to 5;

vinorelbine 25 mg/m2, Day 1; Dexamethasone 10 mg/m2 Days 1 to 5; Methotrexate 3g/m2, 3-hour infusion Day 1; Cyclophosphamide 200 mg/m2, Days 1 to 5; Doxorubicin 25 mg/m2, Days 4 to 5;

Calculated from the time of diagnosis to the first of the following events: progression, relapse, secondary ,malignancy or death

Prognostic value of peripheral blood/bone marrow NPM-ALK or ALK-variants level (qPCR) at diagnosis in pediatric ALCL

Inclusion Criteria: Patient must be ≤ 18 years at the time of diagnosis Newly diagnosed patients with histologically confirmed high-risk anaplastic large cell lymphoma No congenital immunodeficiency, HIV infection, or prior organ transplant Exclusion Criteria: Patients have received prior cytotoxic chemotherapy/target therapy/radiation, if any steroid applied, total prior steroids dosage > Dexamethasone 40 mg/m2 for the current diagnosis or any cancer Patients have overwhelming infection, and a life expectancy of < 2 weeks

Study protocol, SAP and ICF were shared before study initiation. Patient data and the information about the process of the study will be shared within the all participants annually after enrollment patients.

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