Clinical Features and Prognosis of Unselected Patients with AML and RAEB-2: Japan Adult Leukemia Study Group CS-07 Study

[Background] In practice, the clinical features of acute myeloid leukemia (AML) and refractory anemia with excess blasts-2 (RAEB-2) are much more heterogeneous than cases selected in clinical trials. It is also not easy in prospective trials to evaluate the efficacy of allogeneic stem cell transplantation during the first remission for AML, since the selection of treatment is not random but is mostly dependent on the donor availability. In Japan Adult Leukemia Study Group CS-07 study, we tried to see the real world of AML and RAEB-2 in Japan, aiming to see the prognosis and the applicability of known prognostic factors for cases in practice, and to address the efficacy of allogeneic stem cell transplantation for AML during the first remission. [Methods] All AML and RAEB-2 cases that were diagnosed at participating institutions were prospectively registered between Mar 2003 and December 2011. Data of 3054 patients from 117 institutes were updated as of June 2016. [Results] Male patients were predominant (n=1,944); female (n=1,100). Mean age at the diagnosis was 61.3 years (range, 15 to 96 years), and the disease type was diagnosed as de novo, secondary, and therapy-related in 2,255, 593, and 206 patients, respectively. Among 2937 patients with available cytogenetic data, 517, 1626, and 794 patients were classified in the favorable-, intermediate-, and adverse-risk group, respectively. Transplantation was performed in 23.3% of cases, and 39.8% were done during the first remission. For AML, the 3- and 5-year overall survival rate (OS) was 36.3% (SE 1.0%) and 32.5% (SE 1.0%), and those for RAEB-2 were 19.4% (SE 2.2%) and 13.3% (SE 4.2%), respectively. OS in favorable-, intermediate-, and adverse-risk group were 89.6% and 80.6%, 75.4% and 48.2%, and 39.7% and 17.3%, respectively, for younger patients (P<.001), and were 69.0% and 56.5%, 49.1% and 37.3%, and 18.9% and 3.7%, respectively, for elderly patients (P<.001). Age group was significantly related with the clinical results. To address the efficacy of allogeneic transplantation during the first remission, the propensity score analysis was performed making nested pairs in these registered cases, in which transplantation did not demonstrate the significant improvement of OS.

[Conclusion] The result of this study would mirror the overall features of AML and RAEB-2 patients in our country, and confirmed the prognostic values of age group, and cytogenetic risk not only in younger but also in elderly patients. The usefulness of allogeneic stem cell transplantation for AML during the first remission needs to be addressed further in "real world" situation.