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Central nervous system (CNS) leukemia: the role of high dose cytarabine (HDAra-C)
E Morra1, M Lazzarino, E P Alessandrino
1Division of Hematology, Istituto Scientifico Policlinico San Matteo, Pavia, Italy.
Insights
Systemic high-dose cytarabine (HDara-C) effectively treats meningeal leukemia in adults with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin
Area of Science:
- Hematology
- Oncology
- Neuro-oncology
Background:
- Leukemia and lymphoma can metastasize to the central nervous system (CNS), forming meningeal disease.
- Effective treatment of CNS involvement is crucial for patient survival and quality of life.
Purpose of the Study:
- To evaluate the efficacy and safety of systemic high-dose cytarabine (HDara-C) for overt meningeal leukemia.
- To assess HDara-C's effectiveness in patients with isolated CNS disease and those with concurrent bone marrow (BM) involvement.
Main Methods:
- 31 adult patients with meningeal leukemia (ALL, ANLL, LBC-CGL, NHL) received systemic HDara-C.
- Treatment involved 8 doses of Ara-C (3 g/m2 i.v. q 12 h) followed by 4 doses at day 21.
- Complete responders received consolidation therapy; some also received additional multidrug consolidation and direct CNS therapy.
Main Results:
- 20 of 31 patients (64%) achieved complete remission (CR).
- CR rates were 100% for isolated meningeal leukemia and 48% for concurrent CNS and BM disease.
- CNS symptoms resolved promptly in most patients, with a median CR duration of 6 months.
Conclusions:
- Systemic HDara-C demonstrates high efficacy in treating acute leukemias and NHL with CNS involvement.
- The regimen is well-tolerated with manageable myelosuppression and no observed neurologic toxicity.
- HDara-C shows potential utility for chemoprophylaxis in high-risk patients for CNS disease.
Abstract:
Knowing the good penetration of systemic HDara-C into the CNS, we treated with this approach overt meningeal leukemia, either isolated or with bone marrow (BM) disease, in 31 adults: 18 ALL, 4 ANLL, 1 lymphoid blast crisis of CGL (LBC-CGL), and 8 non-Hodgkin's lymphoma (NHL). Treatment consisted of Ara-C, 3 g/m2 i.v. q 12 h, by 3 h infusion for 8 doses, followed by 4 doses at day 21. Complete remitters received consolidation with four monthly 4-dose courses of HDara-C. Additional multidrug consolidation and direct CNS therapy with intrathecal (i.t.) methotrexate (MTX) or Ara-C +/- cranial RT was administered to the 11 remitters last treated. Twenty of 31 patients (64%) achieved CR: 10/10 with isolated meningeal leukemia and 10/21 with concurrent CNS and BM disease. Of the remaining 11 patients, 8 had cerebrospinal fluid (CSF) clearing with persistent BM disease. In all cases but one CNS symptoms resolved promptly. CR median duration was 6 months (range 2 to 20). The main toxicity was myelosuppression requiring intensive support. There was no neurologic toxicity. These results show that systemic HDara-C is highly effective in acute leukemias and NHL with CNS involvement, and suggest the utility of this regimen for sanctuary chemoprophylaxis in patients at high risk for CNS disease.