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The Lancet Oncology

Sunday, January 4, 2009

Dexamethasone can Eliminate One-Third of All Relapses in Childhood Acute Lymphoblastic Leukemia

The results from a study conducted by Martin Schrappe, MD, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany showed that the use of dexamethasone, a corticosteroid commonly used to treat inflammation of the skin, joints, lungs and other organs, in the induction phase of combination chemotherapy led to a one-third reduction in the risk of relapse as compared with prednisone, the standard corticosteroid therapy. These results translated into a significant benefit in terms of event-free survival in children with acute lymphoblastic leukemia. Schrappe presented these results during the 50th Annual Meeting of the American Society of Hematology (ASH) in San Francisco, CA (December 6 – 9).

Dexamethasone was associated with a greater risk of severe side effects, mainly invasive infections; hence, more intensive clinical monitoring and, in particular, early antimicrobial therapy in patients should be implemented to preserve the advantage of using dexamethasone, rather than prednisone, as part of induction therapy.

Following a pre-phase treatment regimen of prednisone and intrathecal methotrexate, a total of 3,655 children (ages 1 to 17) from Germany, Italy, Austria, and Switzerland with acute lymphoblastic leukemia were randomized to receive induction therapy consisting of either prednisone (60 mg/m2/d) or dexamethasone (10 mg/m2/d) in addition to vincristine, daunorubicine, and L-asparaginase combination therapy. Post-induction therapy was also given to patients.

Six-year event-free survival reached 84.1 percent in patients who received dexamethasone as compared with 79.1 percent of those who received prednisone in the induction phase. The six-year cumulative incidence of relapse was 11 percent and 18 percent for patients randomized to dexamethasone and prednisone, respectively. The difference between the two groups was observed for bone marrow relapses (8 percent versus 12 percent), central nervous system relapses (2 percent versus 4 percent), and other relapses (2 percent versus 3 percent) in dexamethasone as compared with prednisone.

Higher toxicity was seen in those treated with dexamethasone. The cumulative incidence for death in the induction phase was 2 percent for dexamethasone compared with 0.9 percent for prednisone; however, the cumulative incidence of death during remission was similar between the two treatment groups (2 percent for dexamethasone and 1.6 for prednisone).

Although dexamethasone was associated with a greater risk of severe toxicity, the results of the study show that it leads to a marked reduction of the risk of relapse, translating this into a significant benefits. This was most evident in patients with in vivo sensitivity to the prednisone prephase, while the efficacy of dexamethasone in poor responding patients was not convincing. The researchers conclude that in the future, more intensive clinical monitoring and early anti-infective interventions could render the advantage of using dexamethasone even more evident. They also believe that other, potentially toxic, agents such as anthracyclines may be limited in induction for carefully selected subgroups of patients with the aim of limiting early or late toxicities.

For more information, read:
Schrappe M, Zimmermann M, Möricke A, Mann G, et al. Dexamethasone in Induction Can Eliminate One-Third of All Relapses in Childhood Acute Lymphoblastic Leukemia: Results of an International Randomized Trial in 3,655 Patients (Trial AIEOP-BFM ALL 2000) (Oral Session), Blood (ASH Annual Meeting Abstracts) 2008 112: Abstract #7

Also read PubMed abstracts:
Möricke A, Reiter A, Zimmermann M, Gadner H, et al. Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95.Blood 2008 May 1;111(9):4477-89. Epub 2008 Feb 19.

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