While there is a clear movement away from CR1 transplantation using matched family donors in pediatric patients with AML that has favorable prognostic features, there is evidence suggesting an advantage for allogeneic HSCT in patients with intermediate-risk characteristics. A large intent-to-treat analysis of 472 young adults treated on Bordeaux Grenoble Marseille Toulouse (BGMT) studies showed a survival benefit from allogeneic HSCT in intermediate-risk patients (all patients not favorable or unfavorable), while patients with favorable risk disease [M3, t(8:21), or inv (16)] did not appear to benefit. Of note, there were insufficient numbers in the study to determine whether patients with unfavorable-risk disease [complex karyotype (?5 cytogenetic findings), del(5q), monosomy 5 or 7, 3q rearrangements, t(9;22), t(6;9), or 11q23 rearrangements, except t(9;11)] benefit from this approach. A second study combining the results of the POG-8821, CCG-2891, COG-2961, and MRC-Leuk-AML-10-Child studies confirmed an advantage for allogeneic HSCT in intermediate-risk patients (not favorable-risk as defined above or poor-risk, defined below). However, again, there were insufficient numbers in this study to assess the role of matched family member transplantation in poor-risk patients (delq), monosomy 5 or 7 or >15% blasts after first induction for POG/CCG studies, additionally 3q abnormalities and complex cytogenetics for the MRC study). Because definitions of high-, intermediate-, and low-risk patients are evolving due to the ongoing association of molecular characteristics of the tumor with outcome (i.e., FLT-3 internal tandem duplications, WT1 mutations, etc.), further analysis of subpopulations of patients treated with allogeneic HSCT will be an ongoing need in current and future clinical trials. Based on a published retrospective study of 95 children who received unrelated cord blood (UCB) transplantation for AML, the Eurocord Group is recommending UCB transplantation for children who have very poor prognosis AML and who lack an HLA-identical sibling. Poor-risk AML was defined as that having cytogenetics with any of the following abnormalities: monosomy 5 and 7, del(5q), 11q23 abnormalities other than t(9;11), abnormal 3q, t(6;9), or complex karyotypes.
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 with two randomized studies failing to show benefit for maintenance therapy with interleukin-2.[3,6,22]
Treatment Options Under Clinical Evaluation
The following is an example of a national and/or institutional clinical trial that is currently being conducted. Information about ongoing clinical trials is available from the NCI Web site.
- AML08: 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.