Results of the AIEOP AML 2002/01 multicenter prospective trial for the treatment of children with acute myeloid leukemia

Abstract

Key Points• Risk-adapted therapy and broad use of HSCT resulted in a significant improvement in outcome.• AUTO-or ALLO-HSCT in high-risk patients resulted in a cumulative incidence of leukemia relapse superimposable to that of SR.We evaluated the outcome of 482 children with acute myeloid leukemia (AML) enrolled in the Associazione Italiana di Ematologia e Oncologia Pediatrica AML 2002/01 trial. Treatment was stratified according to risk group; hematopoietic stem cell transplantation (HSCT) was used in high-risk (HR) children. Patients with core binding factor leukemia achieving complete remission (CR) after the first induction course were considered standard risk (SR; 99 patients), whereas the others (n 5 383) were assigned to the HR group. Allogeneic (ALLO) or autologous (AUTO) HSCT was employed, respectively, in 141 and 102 HR patients after consolidation therapy. CR, early death, and induction failure rates were 87%, 3%, and 10%, respectively. Relapse occurred in 24% of patients achieving CR. The 8-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 68%, 55%, and 63%, respectively. OS, EFS, and DFS for SR and HR patients were 83%, 63%, and 66% and 64%, 53%, and 62%. DFS was 63% and 73% for HR patients given AUTO-HSCT and ALLO-HSCT, respectively. In multivariate analysis, risk group, white blood cell >100 3 10 9 /L at diagnosis, and monosomal karyotype predicted poorer EFS. Risk-oriented treatment and broad use of HSCT result in a long-term EFS comparing favorably with previously published studies on childhood AML. (Blood. 2013; 122(2):170-178)

Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study.

“…10,25,26 The outcome of children transplanted from UDs acquires particular value in light of the fact that this type of allograft was employed in patients either with poor-prognosis molecular lesions, such as FLT3-ITD, or in infants, or in children with M7-AML or complex karyotype or in those patients not responding to the first course of induction therapy, these subgroups notoriously predicting a grim prognosis. 2,8,17,27,28 We and others have previously provided evidence that the outcome of children with acute lymphoblastic leukemia given HSCT from an UD has improved over time, 12,13,26 and the present results confirm that currently, thanks to the improvements in HLA typing obtained through the use of high-resolution molecular techniques and the optimization of GVHD prevention and treatment, post-transplantation outcome is not influenced by the type of donor used, either related or unrelated.…”

“…These considerations must certainly be put forward also in our cohort of patients, which, however, did not include any child with acute promyelocytic leukemia or core-binding factor anomalies. As we previously reported, 17 37 HR patients (11% of the whole HR population included in the AIEOP-2002/01 protocol) received neither AUTO-nor ALLO-HSCT at the end of consolidation therapy. These patients had a significantly worse outcome in comparison with those given HSCT.…”

“…We have previously demonstrated that a broad use of HSCT in this HR population is able to lower the CI of relapse to an extent comparable to that of SR children, 17 suggesting that transplantation can abolish the detrimental impact mainly imparted by specific molecular lesions and poor response to therapy.…”

“…In the successor protocol, the AIEOP group will not use AUTO-HSCT and will restrict the indications to ALLO-HSCT to a population of patients (40-45% of the total number of children with AML other than acute promyelocytic leukemia instead of the 75-80% of patients who were given HSCT in the protocol AIEOP 2002/01) with biological and treatment-related characteristics predicting poor outcome if treated with chemotherapy only (see Pession et al 17 and Hasle 36 for details).…”

“…5,16 We recently reported that risk-oriented treatment and broad use of HSCT in children with CR1 AML resulted in a long-term outcome, which compares favorably with that reported in other patient series. 17 In this study, we thoroughly analyze the results of the 243 HR children enrolled in the AIEOP AML 2002/01 protocol, who were given either AUTO or ALLO HSCT for consolidating remission after achievement of CR1.…”