Blast localization in the brain occurring at diagnosis or at relapse in AL and in NHL patients is considered an adverse prognostic event. The management of meningeal or CNS disease includes intrathecal (IT) injection of cytotoxic drugs (methotrexate, cytarabine, steroids), cranial radiotherapy and high dose chemotherapy. IT therapy is currently carried out by weekly or biweekly drug administration, until clearance of leukemic cells from CSF.

Liposomal cytarabine (Depocyte®), a newcomer in the strategy of lipid incapsulation of cytotoxic drugs, is a molecule registered exclusively for IT administration in lymphomatous meningeal diseases. Because of its long-lasting clearance profile, this drug can be administered every two weeks, thus resulting in better patient compliance.

From September 2004 to April 2006, we treated 8 patients by IT Depocyte at the standard dose of 50 mg every two weeks, for a total of 25 doses. Three patients had acute leukemia: 2 ALL, 1 AML; 24, 54, and 55 year-old, respectively. At time of meningeal involvement, two patients were also in hematological relapse, while the other was in complete hematological remission. The patients had been previously treated by cytotoxic chemotherapy according to the current protocols; intrathecal prophylaxis with MTX and methylprednisolone had also been administered to ALL patients.

A 46 year-old patient, had CML in blast crisis (CML-BP), with blast cells expressing both myeloid and lymphoid markers (CD 34+, CD19+, CD10+, CD24+, CD79a+, TdT+, CD33+, CD13+, CD11b+, CD7+). The blast crisis, involving simultaneously bone-marrow and CNS, had occurred during treatment with imatinib. Two elderly patients (> 60 year-old) suffering from NHL (mantle-cell and diffuse large-B-cell histotypes, respectively, had showed CNS localization (meningeal and meningeal + right orbital mass) during their disease progression. Two young patients, aged 28 and 39 yrs, suffered from primary cerebral (PCNS) lymphoma.

7/8 patients had blast cells detectable at CSF examination (mean, 857/μL; range, 23 – 2500/μL).

AL patients received four doses of Depocyte as unique IT drug, and all showed early and complete clearance of blast cells from CNS. In the patient with CML-BP, CSF was not cleared after two doses of the drug, and the treatment was interrupted. As for NHL patients, the one with mantle cell lymphoma received the four scheduled Depocyte injections, and showed complete remission of the meningeal localization, while the other stopped the treatment after the 2nd dose because of CNS disease progression. Both patients with PCNS lymphoma received only two doses of Depocyte because of rapid neurological deterioration.

No patient showed toxicity or adverse events due to the IT administration of liposomal cytarabine. In responding patients (4/8), CSF leukemic cell count fell rapidly after the first IT injection, and none of them had further meningeal involvement at hematological disease progression.

Intrathecal therapy with Depocyte appears feasible, well tolerated and effective in patients with meningeal leukemic/lymphomatous disease, while it was ineffective, at least in our hands, in patients suffering from primary CNS lymphoma, for which the gold standard of treatment remains systemic high dose methotrexate and cytosine arabinoside followed by radiation therapy.

Topics:
central nervous system dysfunction, cytarabine, leukemia, acute, liposomes, lymphoma, non-hodgkin, colony-stimulating factors, cytotoxic drug therapy, blast phase, leukemic cells, lymphoma

Disclosures: Michele Elefanti and Silvia Ferreri are employees of Mundipharma.

Author notes

*

Corresponding author

2006, The American Society of Hematology
2006
Sign in via your Institution