Isolated leptomeningeal relapses in high-risk neuroblastoma

Background. Neuroblastoma (NB) is the most common extracranial solid malignant tumor of childhood, about 50 % of patients with NB are stratified into a high-risk (HR) group at the time of diagnosis. Despite the multimodal approach to therapy, half of the patients develop relapse of the disease, affecting mostly bones and bone marrow. Relapses with localization in the central nervous system (CNS) are extremely rare and are predominantly parenchymal in nature. Isolated leptomeningial involvement at relapse is an incredibly rare (0.6 % of all relapses), but is characterized by extremely aggressive manifestation and associated with unfavorable prognosis.

Materials and methods. A description of three clinical cases of CNS relapses with isolated leptomeningeal lesions in patients with HR NB treated at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia.

Results. The study included 3 patients with isolated leptomeningeal relapse of NB. The age at the time of the initial diagnosis was 23, 36, and 80 months. Initially, the patients were stratified into a HR group according to the GPOH NB-2004 protocol. Amplification in the MYCN gene was detected in two patients, gain MYCN in one; deletion of the 1p chromosomal region was also detected in two patients, and deletion of the 11q chromosomal region in one patient. Two patients had a mutation in the ALK gene: in one case, the mutation was found in the primary tumor tissue, in the other – in the relapse tumor tissue. The time from the initial diagnosis to the detection of leptomeningeal recurrence of the disease was 5, 15 and 16 months. In two cases, CNS relapse debuted with the appearance of clinical symptoms, in one case it was detected during a follow-up examination. All patients received anti-relapse therapy with drugs that penetrate the blood-brain barrier, two received molecular-directed therapy with ALK inhibitors, and only one patient received craniospinal irradiation and intrathecal administration of a chemotherapy drug.

Two patients died as the disease progressed. One patient is alive at the time of the publication without disease progression, the follow-up time is 9 months from the diagnosis of relapse.

Conclusions. Leptomenigial CNS lesion in relapse NB may be characterized by a non-specific clinical presentation requiring a differential diagnosis with the toxicity of therapy. Comprehensive therapeutic approach with chemotherapy, radiation therapy, and intrathecal administration of drugs is needed to improve the long-term survival of this subgroup of patients.

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