Liposomal Cytarabine Is Effective and Tolerable in the Treatment of Central Nervous System Relapse of Acute Lymphoblastic Leukemia and Very Aggressive Lymphoma

Haematologica. 2011 Feb;96(2):238-44. doi: 10.3324/haematol.2010.028092. Epub 2010 Oct 15.

Abstract

Background: Treatment of central nervous system relapse in adult acute lymphoblastic leukemia is a challenge and outcome is poor. Liposomal cytarabine has a prolonged half-life and, given intrathecally, has produced high response rates in patients with central nervous system relapse of non-Hodgkin's lymphoma. The aim of this study was to evaluate the efficacy and tolerability of liposomal cytarabine in central nervous system relapse of acute lymphoblastic leukemia or Burkitt's lymphoma/leukemia.

Design and methods: Liposomal cytarabine (50 mg) was given intrathecally together with systemic or intrathecal dexamethasone once every 2 weeks in a phase II European trial. The primary end-point, cytological response in the cerebrospinal fluid after one or two cycles, was evaluated at the time of next treatment.

Results: Nineteen heavily pretreated patients (median age, 53 years; range 24-76 years) were evaluable: 14 with acute lymphoblastic leukemia and 5 with Burkitt's lymphoma/leukemia). Complete cytological remission as best response after two cycles of liposomal cytarabine was confirmed in 74% of the patients: 86% of those with acute lymphoblastic leukemia and 40% of those with Burkitt's lymphoma/leukemia). Nine of the 14 patients who achieved complete remission relapsed after a median of 7 months. The median overall survival was 11 months. Adverse events were observed in 89% of the patients (57% of cycles). Grade III-IV events with potential correlation to liposomal cytarabine occurred in 32% of the patients. The most frequent adverse event was headache. One patient developed severe neurological complications with loss of vision and a conus syndrome.

Conclusions: Overall, liposomal cytarabine showed excellent antileukemic activity. Toxicity was acceptable but appeared to increase with the number of cycles. Future evaluation in prophylaxis is of interest.

Trial registration: ClinicalTrials.gov NCT00199108.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Burkitt Lymphoma / complications
  • Burkitt Lymphoma / drug therapy*
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / etiology
  • Cytarabine / therapeutic use*
  • Female
  • Humans
  • International Agencies
  • Liposomes
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prospective Studies
  • Risk Factors
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • Liposomes
  • Cytarabine

Associated data

  • ClinicalTrials.gov/NCT00199108