Idarubicin Based Regimen For Patients With Hematologic Malignancies Involving Central Nervous System

Background and AimHematological malignancies involving central nervous system (CNS) still pose a challenge to clinicians. They always do not respond well to the conventionally used protocols due to the poor penetration of blood-brain-barrier. The prognosis generally has been poor. Optimal treatment of CNS hematological diseases remains poorly defined. An idarubicin based regimen in the treatment of hematological malignancies with central nervous system involvement has been developed and evaluated in 15 patients.MethodsBetween April 2003 and July 2005 a total of 15 patients with hematologicalmalignancies involving central nervous system were enrolled onto the study. General status, clinical manifestations, laboratory findings and reaction to the chemotherapy of the 15 patients were reviewed. Patients were followed carefully for the toxicities and response to treatment. ResultsBetween April 2003 and July 2005 a total of 15 patients were enrolled onto the study. There were 8 men and 7 women, with a median age of 52 years. There patients with primary CNS lymphoma (PCNSL) and 5 patients with secondary CNS lymphoma (SCNSL) were treated with ITD regimen which comprises idarubicin lOmg/d, intravenously (i.v.) on Days 1-3;teniposide lOOmg/d, i.v. on Days 1-3;dexamethasone 30mg/d, i.v. on Days 1-3, repeated every 4 weeks. Six patients with acute leukemia, all of whom had CNS relapse, were treated with ITA regimen which comprises idarubicin lOmg/d, i.v. on Days 1-3;teniposide lOOmg/d, i.v. on Days 1-3;sytosine arabinoside (ARA-C) lOOmg/d, i.v. on Days 1-5;repeated every 4 weeks. Doses of intrathecal methotrexate and dexamethasone were given to patients who had involvement in the cerebrospinal fluid. Patients were followed carefully for the toxicities and response to treatment. Predictable neutropenia and thrombocytopenia occurred in the majority of patients. Of the 9 patients with CNS lymphoma, 4 achieved complete remission (CR), 3 achieved partial remission (PR), 1 died of cerebral hemorrhage two days after the delivery of chemotherapy and 1 died of heart attack. The first patient treated with ITD regimen remained CR for 29 months at the last follow-up. Of the 6 patients with acute myelocytic leukemia (AML), all of them achieved CNS leukemiaremission and 4 got bone marrow CR simultaneously. One patient remained CR for 11 months at the last follow-up. The other 5 patients died of disease progression. The median time to progression was 10 months.ConclusionThis study suggests that the idarubicin based regimen is effective in hematologic malignancies involving central nervous system. Further development and evaluation is suitable. The ITD regimens seems to be suitable for patients with CNS lymphoma as the "induced protocol". Since the goal of treatment of CNS leukemia is palliative and meant to improve or delay progression of neurologic symptoms and signs, the ITA protocol can pretend as an salvage regimen for those patients. But because of the comparative rarity of cases, further development and evaluation is urgently needed.