Results and Discussion
We identified a total of 179 records, according to our selection criteria. Thirty-eight studies were duplicate and excluded. A total of 141 peer-reviewed papers were screened, based on this review’s focus: ALCL in pediatric patients with CNS involvement. Thus, 132 not relevant papers were excluded.
Only 9 pediatric cases of primary CNS ALCL were reported in literature (TABLE 1)4-12. In five out of nine, the initial clinical suspicion concerned an infectious disease. In our case, the radiological features, symptoms and the absence of any nodal involvement, had supported the hypothesis of meningioma. Therefore, safe complete surgical removal was planned. However, general conditions can easily deteriorate and the disease can be so aggressive that multi-nodal involvement can be detected soon after surgery.
CNS ALK+ALCL (a T- cell lymphoma) is an exceptional subtype in pediatric patients. Metastasis, multiple organ failure, and intracranial hypertension are the most frequent causes of death. There is no standard treatment because of its rarity, and the role of neurosurgery varies in different case series. Surgical excision is usually performed in case of a single lesion in a safe site. However, the degree of surgical removal does not affect the prognosis. No standard medical treatment has been established. High dose methotrexate (3,5g/m2) is an important induction chemotherapy, and the addition of high-dose cytarabine is advised in younger patients. Cyclophosphamide, doxorubicin, vincristine and prednisolone therapy is transiently efficient, but CNS ALCL becomes rapidly resistant because of the inadequate penetration of drugs through the BBB. There is no evidence regarding whether brentuximab vedotin can cross the BBB, whereas intrathecal methotrexate therapy is often added to intravenous chemotherapy, in order to treat and protect CNS from recurrence. The use of allogeneic hematopoietic stem cells transplantation as consolidation therapy, results in 5- years post-relapse survival over 50% with OS of 77%. Radiation therapy should be considered as a part of consolidation, but it is associated with an increase of neuro-cognitive deficits. ALK-inhibitors (alectinib and crizotinib) have been evaluated in trials recruiting patients with refractory/relapsing ALCL ALK+ tumors. Crizotinib was approved by FDA in USA in January 2021, for treatment of pediatric patients one year of age, and young adults with relapsed or refractory ALCL. Some case series reported that mono-therapy with ALK inhibitors at relapse, guarantees 70-90% response rates with manageable acute toxicity13-15. Potential long-term effects, such as ocular and endocrine toxicity, need to be addressed. Clinicians are currently investigating the efficacy of the inclusion of ALK inhibitors in front-line therapy, in order to decrease acute chemotherapy toxicity and evaluating an ALK inhibitor with good CNS penetrance, and to decrease the risk of CNS recurrence. Symptoms at the onset are nonspecific for this condition. CNS ALCL is often misdiagnosed as infection, and treated accordingly.
Therefore, primary CNS lymphoma should always be considered in differential diagnosis, in order to manage correct multidisciplinary approach and, whenever possible, promptly start chemotherapy. Due to the aggressiveness of the disease, we decided to treat our patient with standard non-Hodgkin Lymphoma Protocol (LNH97) with adjunctive intrathecal chemotherapy. The boy is currently in complete remission 10 months from stop-therapy.