HOUSTONA modified "hyper-CVAD" (cyclophosphamide [Cytoxan, Neosar], vincristine, doxorubicin(Drug information on doxorubicin) [Adriamycin], dexamethasone(Drug information on dexamethasone)) regimen, which included the addition of rituximab(Drug information on rituximab) (Rituxan) for CD20-positive patients and the use of laminar airflow rooms for patients who were elderly or had poor performance status, reduced induction mortality in older patients with acute lymphoblastic leukemia (ALL). Overall mortality was not changed, because a number of patients died of other causes while in complete remission (CR).Deborah A. Thomas, MD, presented a poster at the 43rd Annual Meeting of the American Society of Hematology describing outcomes in 71 patients with newly diagnosed or primary refractory ALL treated with the modified regimen (see Table 1). She is assistant professor in the Department of Leukemia at The University of Texas M. D. Anderson Cancer Center in Houston.
Induction-Related Toxicity Was Significant
The reported CR rate with hyper-CVAD in an earlier study was 90%, and the 3-year disease-free survival rate was 38%, but at the cost of significant induction-related toxicity. The M. D. Anderson investigators developed a modified hyper-CVAD regimen in the hope of reducing induction mortality, which was 17% in patients aged 60 or older vs 3% in younger patients. The researchers also hoped to lengthen disease-free survival by using early anthracycline intensification and by using rituximab to counter the worse survival associated with CD20 expression. They also hoped to reduce the previously reported central nervous system (CNS) relapse rate of 6% and 1% in low- and high-risk patients, respectively, and to reduce the number of late relapses.
From May 2000 to July 2001, 71 newly diagnosed or primary refractory patients were treated with the modified regimen. These had a median age of 44 years (range: 18-83), with 27% over 60. Forty-two percent were CD20-positive, and 8% had the t(9;22) marker.
The overall response rate was 98%. There was only one death related to induction therapy. It was due to extensive tumor infiltration of bowel with perforation following induction therapy. Dr. Thomas said that this showed that adding rituximab to the regimen did not appear to increase myelosuppressive toxicity. With a median follow-up of 5 months, there were relapses in seven patients (10%), including two isolated CNS relapses at 25 and 28 weeks despite aggressive intrathecal therapy treatment. Five patients had systemic relapses, all of whom were younger patients with high-risk features, according to Dr. Thomas.