Postremission Therapy for AML
Many, but not all, pediatric clinical trial groups prescribe allogeneic HSCT for high-risk patients in first remission. For example, the Children's Oncology Group (COG) frontline AML clinical trial (COG-AAML1031) prescribes allogeneic HSCT in first remission only for patients with predicted high risk of treatment failure based on unfavorable cytogenetic and molecular characteristics and elevated end-of-induction MRD levels. On the other hand, the AML-BFM 2004 clinical trial restricts allogeneic HSCT to patients in second CR and to refractory AML based on results from their AML-BFM 98 study showing no improvement in DFS or OS for high-risk patients receiving allogeneic HSCT in first CR. Additionally, late sequelae (e.g., cardiomyopathy, skeletal anomalies, and liver dysfunction or cirrhosis) were increased for children undergoing allogeneic HSCT in first remission on the AML-BFM 98 study. Because definitions of high-, intermediate-, and low-risk AML are evolving due to the ongoing association of molecular characteristics of the tumor with outcome (e.g., FLT-3 internal tandem duplications, WT1 mutations, and NPM1 mutations) as well as response to therapy (e.g., MRD assessments postinduction therapy), further analysis of subpopulations of patients treated with allogeneic HSCT will be an ongoing need in current and future clinical trials.
Maintenance chemotherapy has been shown to be effective in the treatment of acute promyelocytic leukemia (APL). In other subtypes, there are no data that demonstrate that maintenance therapy given after intensive postremission therapy significantly prolongs remission duration. Maintenance chemotherapy failed to show benefit in two randomized studies,[3,23] and maintenance therapy with interleukin-2 also proved ineffective.
Treatment Options Under Clinical Evaluation
The following are examples of national and/or institutional clinical trials that are currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
- AML08(Clofarabine Plus Cytarabine Versus Conventional Induction Therapy and a Study of Natural Killer Cell Transplantation in Newly Diagnosed AML): St. Jude Children's Research Hospital is conducting a randomized trial for children with newly diagnosed AML in which the efficacy of postchemotherapy NK cell transplantation is being assessed after five cycles of chemotherapy.
- COG-AAML1031 (Bortezomib and Sorafenib Tosylate in Patients With Newly Diagnosed AML With or Without Mutations): This is a phase III COG study designed to answer the question of whether the addition of the proteasome inhibitor bortezomib to chemotherapy during induction and postremission therapy improves outcome; in addition, this study will test whether the addition of sorafenib to chemotherapy along with HSCT for patients with high-allelic ratio FLT3-ITD–positive AML improves outcome compared to historical controls. This study will also utilize MRD determination at the end of induction, in addition to cytogenetics and molecular markers, to stratify postremission therapy.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with childhood acute myeloid leukemia in remission. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.