Risk-Stratified Therapy and the Intensive Use of Cytarabine Improves the Outcome in Childhood Acute Myeloid Leukemia: The AML99 Trial From the Japanese Childhood AML Cooperative Study Group

117

Survival of pediatric acute myeloid leukemia (AML) has improved considerably over the past decades. Since 1985, allogeneic stem cell transplantation (allo-SCT) is widely recommended for patients who have a matched sibling donor. However, it remains controversial whether allo-SCT is superior to chemotherapy for children with newly diagnosed AML. This review summarizes phase 3 clinical trials that compared allo-SCT with chemotherapy (including autologous SCT) in pediatric AML, excluding studies that did not use the intention-to-treat analysis or correct for time-to-transplantation. Although allo-SCT might prevent more relapses than chemotherapy, the number needed for transplantation (with allo-SCT) to prevent one relapse is in the order of 10 patients. Moreover, overall survival is similar with both methods in most recent studies, apparently because of increased salvagability of a relapse when initial therapy concerned chemotherapy only, and because of a higher treatment-related mortality with allo-SCT. Because allo-SCT also gives more severe side effects and results more often in secondary malignancies than chemotherapy, we do not recommend allo-SCT in first remission for pediatric AML in general. Further research should focus on the possibility that subgroups might benefit from allo-SCT, aiming at further improvements in the prognosis of pediatric AML. (Blood. 2010;116(13):2205-2214)

Section: Discussionmentioning

confidence: 98%

“…The 5-year OS of 16 HR patients who underwent allo-SCT (6 related SCT, 6 unrelated SCT, and 4 cord blood SCT) was 69%. 31 …”

Section: Japanmentioning

confidence: 99%

A review on allogeneic stem cell transplantation for newly diagnosed pediatric acute myeloid leukemia

Niewerth

Creutzig

Bierings

et al. 2010

117

“…11,[20][21][22] Data on the benefit of allo-HSCT in AMKL are conflicting. [1][2][3]10 We found no benefit of allo-HSCT in first CR, although criteria for allo-HSCT differed among protocols.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study

Inaba

Zhou

Abla

et al. 2015

Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age £18 years) with non-Down syndrome de novo AMKL diagnosed from 1989 to 2009. Patients with AMKL (median age 1.53 years) comprised 7.8% of pediatric AML. Five-year event-free (EFS) and overall survival (OS) were 43.7% 6 2.7% and 49.0% 6 2.7%, respectively. Patients diagnosed in 2000 to 2009 were treated with higher cytarabine doses and had better EFS (P 5 .037) and OS (P 5 .003) than those diagnosed in 1989 to 1999. Transplantation in first remission did not improve survival. Cytogenetic data were available for 372 (75.9%) patients: hypodiploid (n 5 18, 4.8%), normal karyotype (n 5 49, 13.2%), pseudodiploid (n 5 119, 32.0%), 47 to 50 chromosomes (n 5 142, 38.2%), and >50 chromosomes (n 5 44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: 121 (n 5 106, 28.5%), 119 (n 5 93, 25.0%), 18 (n 5 77, 20.7%). Losses occurred in 65 patients (17.5%): -7 (n 5 13, 3.5%). Common structural chromosomal aberrations were t(1;22)(p13;q13) (n 5 51, 13.7%) and 11q23 rearrangements (n 5 38, 10.2%); t(9;11)(p22; q23) occurred in 21 patients. On the basis of frequency and prognosis, AMKL can be classified to 3 risk groups: good risk-7p abnormalities; poor risk-normal karyotypes, -7, 9p abnormalities including t(9;11)(p22;q23)/MLL-MLLT3, -13/13q-, and -15; and intermediate risk-others including t(1;22)(p13;q13)/OTT-MAL (RBM15-MKL1) and 11q23/MLL except t(9;11). Risk-based innovative therapy is needed to improve patient outcomes. (Blood. 2015;126(13):1575-1584

“…23 For example, the Japanese Childhood AML Cooperative Study Group reported recently a 5-year survival of 86% Ϯ 6% and EFS of 71% Ϯ 8% for low-risk patients, which mainly included patients with t(8;21) on the AML99 trial. 24 These patients were treated with 5 consolidation courses, including cytarabine with a dosage up to 3 g/m 2 . Similarly, the 7-year survival for CBF-AML patients [18 patients with t(8;21) and 10 patients with inv(16)] on the AML-93 trial of the Nordic Society for Paediatric Hematology and Oncology was 77% Ϯ 10%, using a regimen including 4 courses of HDAC-based therapy.…”

Section: Discussionmentioning

confidence: 99%

Second induction with high-dose cytarabine and mitoxantrone: different impact on pediatric AML patients with t(8;21) and with inv(16)

Creutzig

Zimmermann

Bourquin

et al. 2011

Patients with core binding factor acute myeloid leukemia (CBF-AML) benefit from more intensive chemotherapy, but whether both the t(8;21) and inv(16)/t (16;16) subtypes requires intensification remained to be determined. In the 2 successive studies (AML-BFM-1998 and AML-BFM-2004), 220 CBF-AML patients were treated using the same chemotherapy backbone, whereby reinduction with high-dose cytarabine and mitoxantrone (HAM) was scheduled for these cohorts only in study AML-BFM-1998 but not in AML-BFM-2004 against the background to minimize overtreatment. Five-year overall survival (OS) and event-free survival (EFS) were significantly higher and the cumulative incidence of relapse (CIR) lower in t(8;21) patients treated with HAM (n ‫؍‬ 78) compared with without HAM (n ‫؍‬ 53): OS 92% ؎ 3% versus 80% ؎ 6%, p logrank 0.047, EFS 84% ؎ 4% versus 59% ؎ 7%, p logrank 0.001, and CIR 14% ؎ 4% versus 34% ؎ 7%, p (gray) 0.006. These differences were not seen for inv (16)