Transplant-finalized salvage of adult acute lymphoblastic leukemia: results of a mitoxantrone- and methotrexate-based regimen in 36 patients

Leuk Lymphoma. 2005 Jun;46(6):879-84. doi: 10.1080/10428190500080801.

Abstract

Idarubicin-based induction programs in acute lymphoblastic leukemia (ALL) account for 75?-?85% of complete remission rate. A small amount of patients exhibit primary refractoriness, and approximately 60% of those achieving a remission eventually relapse. The present study aimed to review the outcome of patients relapsing after or resistant to an idarubicin-based, induction-consolidation regimen (with/without additional high dose cytarabine). The 'ABC' phase II trial consisted of mitoxantrone (50 mg/m(2) over 5 days) associated with high-dose methotrexate (1.5 g/m(2) over 24 h, followed by folinic acid rescue), high-dose methyl-prednisolone (125 mg b.i.d.) and vincristine, plus granulocyte colony-stimulating factor. Eligible patients were treated with two courses ('A' and 'B', the latter with reduced drug dosages), followed by allogeneic or autologous haematopoietic stem cell transplantation (HSCT, 'C'). Thirty-six patients (3 primary resistant, 33 at first marrow relapse) were evaluated. With 'A', 21 achieved a complete remission (CR), 10 were refractory and 5 died early. Eighteen patients received 'B' (with one more CR, for an overall CR rate of 61%) and, eventually, 12 patients had 'C' procedures (7 autologous, 5 allogeneic HSCT). WHO grade >or=3 treatment-related toxicity developed in 50% and 34% of 'A' and 'B' courses, respectively. The median duration of CR was 5.2 (range 0.5-19.7) months and median overall survival was 7.6 (range 0.5-20) months. In spite of 12 HSCTs, there was no long-term survivor. 'ABC' salvage proved feasible and comparable to reported rescue chemotherapic regimens, but the achievement of cure in refractory/relapsing ALL remains an outstanding clinical task.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bone Marrow Transplantation
  • Female
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Male
  • Methotrexate / administration & dosage*
  • Middle Aged
  • Mitoxantrone / administration & dosage*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Remission Induction
  • Treatment Outcome
  • Vincristine / therapeutic use

Substances

  • Granulocyte Colony-Stimulating Factor
  • Vincristine
  • Mitoxantrone
  • Methotrexate