ATAXIA-TELANGIECTASIA-ASSOCIATED PEDIATRIC HODGKIN LYMPHOMA: HIGH INITIAL CHEMOSENSITIVITY BUT DISMAL SURVIVAL

Nesreen Ali1, Hany Abdelrahman1, Emad Moussa 2, Nesreen Radwan 3, Eman Khorshed 4, Sara Badawy5 , Walaa Elsayed1

1-PediatricOncology and Haematology Department, National Cancer Institute (NCI), Cairo University and Children Cancer Hospital Egypt (CCHE-57357), Cairo, Egypt ,2-Clinical Oncology Department, Menoufya University and Children Cancer Hospital Egypt(CCHE-57357), Cairo, Egypt,3-Pediatric Allergy, Immunology & Rheumatology Unit, Children’s Hospital, Ain Shams University, Cairo, Egypt. Pediatric Department, Children’s Cancer Hospital Egypt (CCHE 57357), Cairo, Egypt  4-Pathology Department, National Cancer Institute (NCI), Cairo University and Children Cancer Hospital Egypt (CCHE 57357),, Cairo, Egypt, 4-Radiation Therapy Department, National Cancer Institute (NCI), Cairo University and Children Cancer Hospital Egypt (CCHE 57357), , Cairo, Egypt, 5-Clinical Research Department, Children Cancer Hospital Egypt (CCHE 57357), , Cairo, Egypt

Background: Ataxia-telangiectasia (AT) is a rare inherited disorder associated with immunodeficiency, defective DNA damage response, chromosomal instability, and marked radiosensitivity, predisposing affected children to lymphoid malignancies while substantially increasing treatment-related toxicity. Evidence guiding optimal management of Hodgkin lymphoma (HL) in children with AT remains limited, particularly regarding safe chemotherapy intensity adaptation and supportive care optimization.

Methods: We retrospectively reviewed children with AT diagnosed with HL at Children’s Cancer Hospital Egypt between July 2007 and July 2024. Data collected included clinical presentation, stage, B symptoms, risk group, extranodal disease, histopathology, frontline treatment, dose modifications, number of cycles delivered, interim response assessment, and survival outcomes.

Results: Fourteen patients were identified, with a median age at diagnosis of 9 years (range, 6-17 years); 11/14 were male. Advanced presentation was frequent, with stage IV disease in 7/14 patients (50.0%) and B symptoms in 6/14 (42.9%). Risk stratification showed 7/14 high-risk (50.0%), 5/14 intermediate-risk (35.7%), and 2/14 low-risk disease (14.3%). Histology was predominantly classical HL, with mixed cellularity in 8/14 (57.1%) and nodular sclerosis in 5/14 (35.7%); 1 case showed features intermediate between diffuse large B-cell lymphoma and classical HL. Frontline treatment was heterogeneous and toxicity-adapted: 4/14 patients (28.6%) received AVPC with 50% dose reduction, 3/14 (21.4%) AVPC with 25% dose reduction, 1/14 (7.1%) full-dose AVPC, and 4/14 (28.6%) ABVD. One additional patient (7.1%) received 2 cycles of ABVD with 50% dose reduction and omission of doxorubicin because of marked sensitivity, then shifted to COPDAC with 25% dose reduction. The patient with lymphoma showing intermediate features between diffuse large B-cell lymphoma and classical HL received rituximab alone because of very poor general condition. Eleven patients achieved complete metabolic response after 2 cycles, 1 had progressive disease, and 2 died before response evaluation. Despite the high early response rate, all patients ultimately died, predominantly from non-relapse causes, mainly chest infection, respiratory failure, and septic shock. Median survival was 6 months.

Conclusion: AT-associated pediatric HL appears highly chemosensitive, but outcomes are dominated by extreme non-relapse mortality, mainly related to infectious, pulmonary, and treatment-related complications. These findings underscore the urgent need for AT-adapted treatment strategies that preserve efficacy while minimizing toxicity, together with intensive prophylaxis, pulmonary support, and immune optimization.