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.