A single, high dose of idarubicin combined with cytarabine as induction therapy for adult patients with recurrent or refractory acute lymphoblastic leukemia

The authors tested a novel regimen that emphasized dose intensity of both cytarabine and idarubicin as salvage therapy for patients with recurrent or refractory lymphoblastic disease. This combination was moderately active and acceptably tolerable. It may be a useful regimen for patients attempting to attain a second complete response prior to undergoing potentially curative transplantation.

Abstract

BACKGROUND

The majority of adult patients who are treated for lymphoblastic disease will either develop recurrent disease or will be refractory to their initial therapy. One option for patients with recurrent/refractory disease is to administer a reinduction regimen that employs a dose-intense combination of anthracycline and cytarabine. These salvage regimens are relatively distinct from the traditional vincristine/prednisone-based programs that are used typically as primary induction therapy. The authors studied a regimen that contained high-dose cytarabine and a single high dose of idarubicin as salvage induction therapy for patients with recurrent or refractory lymphoblastic disease.

METHODS

Twenty-nine previously treated adult patients with recurrent or refractory acute lymphoblastic leukemia were treated with a new intensive regimen. Eight patients had primary refractory disease. Twenty-one patients had recurrent disease, and 16 of these patients developed recurrent disease while they were still receiving their primary therapy. The treatment regimen consisted of cytarabine 3.0 g/m² by 3-hour infusion daily for 5 days and idarubicin 40 mg/m² given as a single dose on Day 3. Filgrastim (granulocyte-colony stimulating factor) 5 μg/kg administered subcutaneously every 12 hours was started on Day 7 and was continued until the absolute neutrophil count was > 5000/μL. Response was assessed using standard criteria.

RESULTS

There were 11 complete responses (38%; 95% confidence interval, 20–56%). Four patients subsequently underwent allogeneic bone marrow transplantation. Moderate but acceptable toxicity was observed given the severely myelosuppressive nature of the regimen. There was only one treatment-related death (3%). Two patients, both with significant prior exposure to anthracyclines, suffered reductions in left ventricular function to the 20–30% range during episodes of severe systemic infection. After recovery from infection, the ejection fraction in one patient improved to 50%.

CONCLUSIONS

The authors conclude that this regimen has moderate activity and a relatively low incidence of mortality for this high-risk group of patients. This regimen may be most suitable for patients who can undergo potentially curative allogeneic bone marrow transplantation if they achieve a complete response. Cancer 2002;95:581–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10707