Modified Hyper-CVAD Reduces Induction Mortality in Older ALL Patients

Modified Hyper-CVAD Reduces Induction Mortality in Older ALL Patients

HOUSTON—A modified "hyper-CVAD" (cyclophosphamide [Cytoxan,
Neosar], vincristine, doxorubicin [Adriamycin], dexamethasone) regimen,
which included the addition of 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.

Modified Regimen

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.


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