The dose-dense induction regimen S-HAM (sequential high-dose cytarabine [Cytosar®] and mitoxantrone [Novantrone®] followed by Neulasta® [pegfilgrastim]) delivered in two induction cycles over 11-12 days instead of 25-29 days is highly effective in patients with acute myeloid leukemia (AML) and results in a shorter period of low blood cell counts. The results of this study were published in Blood.
Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood characterized by the rapid, uncontrolled growth of immature white blood cells known as myelocytes. The disease is more common in adults than in children; the average age at diagnosis is older than 65 years.
Treatment of AML often begins with induction therapy, where chemotherapy is used to produce a complete remission (the disappearance of leukemia cells in the bone marrow and normalization of the white blood cell, red blood cell, and platelet levels). After induction therapy, patients generally receive additional treatment (consolidation therapy) to reduce the likelihood of a leukemia recurrence.
Dose-dense chemotherapy refers to chemotherapy administered with a shortened interval between cycles; for example, chemotherapy that is usually given every three weeks may be given every two weeks. These dose-dense regimens may kill more cancer cells, but they also allow less time for bone marrow recovery and are associated with anemia (low red blood cell level) and neutropenia (low white blood cell level).
Neutropenia increases susceptibility to infection and can become a serious condition for several reasons: many patients who develop neutropenia will require a delay in treatment or a dose reduction (both events can impede full benefits of treatment); patients who develop neutropenia may require hospitalization; and even minor infections can become life-threatening. Neulasta is a drug that is used to stimulate the production of immune cells in order to reduce or prevent neutropenia.
The German AML-Cooperative Group conducted a study that included 172 AML patients who received S-HAM in two induction cycles delivered over 11-12 days instead of the typical 25-29 day schedule, thereby doubling the rate of dose-density. The resulting overall response rate was 83%. Sixty-one percent of patients reached a complete remission, 22% had a complete remission with incomplete peripheral recovery, 7% had persistent leukemia, and 10% died. Estimated survival following treatment with S-HAM was 75%.
The researchers noted that compressing the two induction cycles into the first 11-12 days of treatment resulted in a shortened duration of neutropenia, which lasted 31 days compared with the usual 46 days after induction delivered over a longer period.
The researchers concluded that the dose-dense induction regimen S-HAM delivered over 11-12 days was highly effective in patients with AML, with the added bonus of a shorter period of neutropenia.
 Braess J, Spiekermann K, Staib P, et al. Dose-dense induction with sequential-high-dose cytarabine and mitoxantrone (S-HAM) and pegfilgrastim results in a high efficacy and a short duration of critical neutropenia in de-novo acute myeloid leukemia – a pilot study of the AML-CG. Blood [early online publication]. January 8, 2009: doi:10.1182/blood-2008-07-162842.