Allogeneic Stem Cell Transplantation (Allo-SCT) in Adults with Acute Myelogenous Leukemia (AML). Final Analysis of JALSG AML97 Study

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is considered to be the most intensive post remission treatment consisting of high-dose chemoradiotherapy and allo-immune mechanisms. However, the powerful anti-leukemic effects of this treatment are counterbalanced by a high incidence of treatment-related mortality (TRM), thus allo- SCT has not always been considered superior to chemotherapy. The aim of this study was to investigate the efficacy of allo-SCT as a postremission treatment in patients with intermediate/poor risk AML in first CR. Previously untreated patients aged 15 – 50 years were eligible. Patients received standard induction therapy consisting of cytarabine (100 mg/ m² d1–7) and idarubicin (12 mg/m² d1- 3). If the patients did not achieve remission after the first induction therapy, then the same induction therapy was given again. The patients who achieved CR were randomized into an intensified short-course postremission chemotherapy group (arm A) or conventional JALSG postremission chemotherapy group (arm B). Patients were also categorized into good, intermediate or poor risk groups by risk factors selected from previous JALSG AML trials using univariate and multivariate analyses. Intermediate or poor risk patients with living siblings were tissue typed. If an HLA matched sibling was found it was assumed that the patient would receive allo-SCT during CR1 (donor group). Those without living or HLA matched siblings were assigned to the no-donor group that continued receiving chemotherapy. The disease-free survival (DFS) rates, the relapse incidence rates (RI), TRM and the overall survival (OS) rates of the patients of the donor group were compared with those of the no-donor group on the basis of the intention to treat.

Result: Of 503 patients aged 15 – 50 years old registered between December 1997 and July 2001, 397 achieved complete remission (CR). The 5-year OS rate of the CR patients with good, intermediate and poor risk was 68%, 43% and 29%, respectively (p<0.001), showing successful stratification by the JALSG scoring system. Among those who achieved CR with intermediate or poor risk, 75 with and 95 without an HLA matched sibling were assigned to the donor and no-donor groups, respectively. The actual risk of relapse at 8 years was significantly lower in the donor group than in the no-donor group (54% versus 78%, p=0.009). The TRM did not significantly differ between the donor group and the no-donor group (16% versus 17%, p= 0.948). The lower relapse rate in the donor group resulted in a significantly better DFS compared with the no-donor group (38% versus 18%, p=0.017). The significant superiority of DFS in the donor group was translated into a higher OS rate, however, the difference in OS between the two groups did not reach statistical significance (45% versus 28%, p=0.089). The OS of the patients younger than 35 years of age were comparable between the donor group and the no-donor group. However, the OS in the donor group patients older than 36 years old was significantly better than the other (47% versus 23%, p= 0.032).

Conclusions: Our study showed that allo-SCT reduced the risk of relapse and contributed to the survival advantage of AML patients aged from 36 to 50 years old with intermediate or poor risk.