Matched-Pairs Analysis Shows Better Survival With Allogeneic Transplantation vs Conventional Chemotherapy in Postremission Therapy for AML
In a prospective matched-pairs analysis reported in the Journal of Clinical Oncology, Stelljes et al in the German AML Cooperative Group compared outcomes with allogeneic stem cell transplantation vs conventional postremission chemotherapy in patients aged < 60 years with acute myeloid leukemia (AML) in first complete remission. They found that stem cell transplantation was associated with significantly better overall survival, including in patients with abnormal karyotype and those aged 45 to 69 years.
Study Details
The study involved analysis of outcomes in 185 pairs of patients aged < 60 years from a large multicenter clinical trial (AMLCG99) in which patients aged < 60 years who had undergone allogeneic stem cell transplantation in first complete remission were matched with patients who received conventional postremission chemotherapy. The primary matching criteria were AML type, cytogenetic risk group, patient age, and time in first complete remission.
The stem cell transplantation and conventional consolidation groups were balanced for age at diagnosis (median, 45 and 46 years), sex (51% and 48% female), karyotype (eg, intermediate-normal in 55% in both, intermediate–not normal in 18% in both), diagnosis (de novo in 85% in both), French-American British classification type (eg, M2 in 33% and 38%, M1 in 23% and 21%), white blood cell count at diagnosis (median, 9.4 and 12.8 cells/nL), lactate dehydrogenase at diagnosis (median, 387 and 408 U/L), randomization for induction therapy (high-dose cytarabine and mitoxantrone [HAM]-HAM in 55% and 50%; thioguanine, standard-dose cytarabine, and daunorubicin [TAD]-HAM in 45% and 50%), and day 15 blasts (median, 5% in both). The median time from complete remission to transplantation was 82 days.
Overall and Relapse-Free Survival
Median follow-up after complete remission was 7.9 years. Projected 7-year overall survival after complete remission was 58% in the transplantation group vs 46% in the conventional therapy group (P = .037). Projected 7-year relapse-free survival was 52% in the transplantation group vs 34% in the conventional therapy group (P < .001). Analysis stratified by patient pairs showed nonsignificantly prolonged overall survival (P = .188) and significantly prolonged relapse-free survival (P < .001) in the transplantation group.
Nonrelapse mortality at 7 years was 24% in the transplantation group vs 6% in the control group (P < .001). The cumulative incidence of AML relapse after 7 years was 36% vs 65% (P < .001). Multivariate analysis adjusting for risk factors showed that allogeneic stem cell transplantation was an independent predictor of improved overall survival (hazard ratio [HR] = 0.66, 95% confidence interval = 0.49–0.89). Independent predictors of poorer survival were older age, unfavorable cytogenetics, and persisting bone marrow blasts (≥ 10%) after the first induction cycle.
Subgroups
Subgroup analyses showed that overall survival was significantly better with allogeneic stem cell transplantation vs conventional therapy in patients with unfavorable chromosomal aberrations (HR = 0.49, P = .006), those with intermediate–not normal karyotype (HR = 0.40, P = .017), those older than 45 years (HR = 0.57, P = .006), those with secondary AML or high-risk myelodysplastic syndrome (HR = 0.37, P = .012), and day 15 blasts < 10% (HR = 0.65, P = .037).
The investigators concluded: “[T]he findings from this prospective matched pairs analysis demonstrate that [allogeneic stem cell transplantation] is the most potent [postremission therapy] for patients with AML in [first complete remission]. In contrast to previously published data, our results indicated that the positive impact of this treatment modality with regard to [overall survival] is especially evident in patients with abnormal karyotype not classified as favorable, including patients with intermediate risk and patients between 46 and 59 years of age.”
Matthias Stelljes, MD, University of Muenster, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Deutsche Krebshilfe, Bundesministerium für Bildung und Forschung, European Commission, and Amgen. The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
