Treatment of refractory acute lymphoblastic leukemia in adults with high dose cytosine arabinoside and mitoxantrone (HAM)

Leukemia. 1990 Sep;4(9):637-40.

Abstract

In a clinical phase II study the combination of high dose cytosine arabinoside and mitoxantrone (HAM) was applied to 24 patients with refractory acute lymphoblastic leukemia (ALL). All patients had received a standardized first line treatment and were considered refractory against conventional chemotherapy as defined by nonresponse to induction treatment (n = 8), nonresponse to an alternative salvage regimen at first relapse (n = 9), second and third relapses (n = 5) and relapse after bone marrow transplantation (n = 2). Therapy consisted of HD-araC 3 g/m2 q 12 hr days 1-4 and mitoxantrone 10 mg/m2/d days 2-5 or 2-6. Twelve of the 24 patients (50%) achieved a complete remission (CR), one patient had a partial remission, and five patients were nonresponders. Five patients died in aplasia due to infections, one additional patient succumbed to HD-araC related CNS toxicity. Nonhematologic side effects consisted predominantly in infection, nausea and vomiting, mucositis and diarrhea. Recovery of blood counts occurred at a median of 28 days from the onset of treatment; the median time to CR was 33 days. Three of the 12 responders underwent subsequent bone marrow transplantations and one is alive disease free at 40+ months. The median remission duration for the remaining nine patients is 3.5 months, with one case in ongoing CCR at 36+ months; the median survival time is 5 months. Considering the selection of a highly unfavorable group of patients, these data demonstrate a significant antileukemic activity of HAM in refractory ALL and support its application as consolidation treatment during first line ALL therapy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow Transplantation
  • Combined Modality Therapy
  • Cytarabine / administration & dosage
  • Cytarabine / adverse effects
  • Diarrhea / chemically induced
  • Drug Evaluation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Mitoxantrone / adverse effects
  • Nausea / chemically induced
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / surgery
  • Remission Induction
  • Vomiting / chemically induced

Substances

  • Cytarabine
  • Mitoxantrone