Abstract
Meningeal localization from hematological malignancies represents a rare event, associated with unfavourable prognosis. Treatment is based on the administration of high doses of drugs able to cross the hemato-encephalic barrier, such as Methotrexate (MTX) and cytarabine (ara-C), cranial and cranial-spinal irradiation and intrathecal (IT) administration of ara-C and/or MTX. These treatments often fail in producing a symptoms improvement and are loaded by an high rate of side effects or by a disconfortable schedule of administration. Depocyte® is a preparation of ara-C englobed in a lipidic multivescicular frame that allows a gradual and harmonic release of the drug for, at least, 14 days. This feature has allowed its utilization in treatment and prophylaxis of CNS localizations in hematological malignancies, being effective in both settings. In our Department. two patients with meningeal localizations from hematological malignancies, have been treated with Depocyte®. Patients characteristics are listed in the table. The former, a female 24 year-old patient, suffered from Burkitt’s lymphoma. After second cycle of therapy in accordance with CHOP scheme, she showed signs and symptoms of meningeal localizations, characterized by cephalea, diplopia with lateral deviation of right eye and, subsequently, seizures. IT treatment with Depocyte® at the dose of 50 mg every 14 days has been started, achieving a partial remission of symptoms, with a reduction of cephalea and of frequency of seizures. The patient died because of a neurological worsening of the disease and its systemic diffusion. The latter, a male 25 year-old patient, suffering from T-ALL, has shown neurological symptoms after a cycle of induction and during CR. Symptoms have been characterized by cephalea and bilateral paralysis of the VII pair of cranial nerves, as well as by dysphagia and difficult deglutition. Treatment with Depocyte® has allowed an improvement of neurological symptoms and blasts disappeared from the CSF. In spite of therapy, remission has resulted short with a relapse of bone marrow desease. Therapy with Depocyte®, in accordance with what is already reported in literature, has proved to be an effective treatment of meningeal localizations, although a complete and lasting remission has not been achieved in our patients, related mainly to the aggressiveness of the underlying disease. However, thanks to its gradual release formulation, Depocyte® allows a lower frequency of IT administrations, compared with traditional drugs; moreover, it has shown a quite good handiness and efficacy in a short-term response of reported patients.
Pazient 1 Pazient 2 Diagnosis Burkitt’s lymphoma T-ALL Age/Sex 24/F 25/M Diagnosis date May 2005 October 2005 CNS Prophylaxis None I.T. MTX Type of relapse Isolated Isolated + Combined Treatment Depocyte® Depocyte® Relapse date August 2005 November 2005 Symptoms III pair of cranial nerves, diplopia, cephalea, seizures VII pair of cranial nerves, cephalea, dysphagia Response (blasts in CNS) N.E. CR Evolution Progression, death Relapse
Rationale for a Combination Therapy Consisting of MCL1- and MEK-Inhibitors in Acute Myeloid Leukemia