Intermediate-Dose Cytarabine in the Treatment of Relapsed or Refractory Leukemias

  • J. L. Harousseau
  • N. Milpied
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 34)


High-dose cytarabine (HD ARA-C) has been extensively used in relapsed acute myeloid leukemia (AML), either alone [1] or in combination with asparaginase [2], daunorubicin (DNR) [3], amsacrine (AMSA) [4], or mitoxantrone [5]. With this high-dose regimen (3 g/m2 twice daily for 4–6 days), high remission reinduction rates have been achieved, but at the expense of significant toxicity, in particular cerebellar toxicity [6]. This complication, which may be irreversible and/or fatal, is dose related and precludes total doses over 48 g/m2 per cycle. It is mainly encountered for total doses of 36 g/m2 (3 g/m2 for 12 doses) or more. The incidence of severe cerebellar toxicity is also related to age, patients >50 years of age having a greater incidence than younger patients [6]. In order to reduce the major toxicities of HD ARA-C, some investigators have used combinations of AMSA or mitoxantrone (MTZ) at optimal dosage with ARA-C at lower cumulative doses [7, 8]. Van Prooijen et al. treated 15 relapsed AML patients with cytarabine (500 mg/m2 every 12 h for 6 days) in combination with doxorubicin and vincristine and obtained 80% CR [9]. Moreover, infusions of ARA-C at doses lower than the standard dose of 3 g/m2 maintain plasma ARA-C levels sufficient to saturate the cellular ARA-CTP accumulation [10]. Thus, cytarabine could be used at intermediate-dose (ID ARA-C) with the same efficacy but less toxicity than in HD ARA-C containing regimens.


Acute Myeloid Leukemia Clin Oncol Acute Leukemia Adult Acute Myeloid Leukemia Relapse Acute Myeloid Leukemia 
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© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • J. L. Harousseau
  • N. Milpied

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