Allogeneic transplantation as post-remission therapy for cytogenetically high-risk acute myeloid leukemia: landmark analysis from a single prospective multicenter trial

Abstract

Background Allogeneic hematopoietic cell transplantation is considered the preferred post-remission therapy in patients with acute myeloid leukemia cytogenetically defined as being at high risk. To substantiate evidence for allogeneic hematopoietic cell transplantation in first complete remission in these high-risk patients we performed a landmark analysis within a single prospective multicenter treatment trial.

Design and methods: By the time of analysis, 2,347 patients had been accrued into the AMLCG 99 trial between 1999 - 2007. Out of this population, 243 patients under 60 years old fulfilled the criteria for high-risk cytogenetics. Landmark analyses were performed with a control cohort, who remained in first complete remission at least the median time from complete remission to transplantation in the intervention group.

Results: After standardized induction therapy, 111 patients under 60 years old achieved complete remission. A matched allogeneic donor was identified for 59 patients (30 sibling donors, 29 unrelated donors). Fifty-five patients received an allogeneic hematopoietic cell transplant after a median time of 88 days in first complete remission. Of the remaining 56 patients, 21 relapsed within 90 days after achieving first complete remission and for 7 patients with relevant comorbidities no donors search was initiated, leaving 28 patients given conventional post-remission therapy as the control cohort. The median follow-up of surviving patients was 60.4 months. Patients with an allogeneic donor had substantially better 5-year overall and relapse-free survival rates than the control group (48% versus 18%, P=0.004 and 39% versus 10%, P<0.001, respectively). A survival benefit from transplantation was evident regardless of donor type, age and monosomal karyotype. Conclusions Beyond evidence available for subgroups of high-risk patients, the findings of this study establish in a broader manner that allogeneic hematopoietic cell transplantation is a preferable consolidation treatment for patients with acute myeloid leukemia and high-risk cytogenetics. The study was registered at Clinicaltrials.gov as NCT00266136.

Figures

Figure 1.

Survival plots for comparison groups. HCT, hematopoietic stem cell transplantation; CR1, first complete remission. Patients transplanted in CR1 (—), landmark control group (—). MUD, matched unrelated donor (—); MRD, matched related donor (—).

Figure 2.

Survival plots for corresponding intent to treat analyses (recommended allogeneic HCT, initiation of donor search and identification of a suitable allogeneic donor as defined per protocol (—); versus patients with recommended allogeneic HCT, initiation of donor search but without identification of a suitable donor as defined per protocol for patients who otherwise were eligible for an allogeneic transplant(—).

Figure 3.

Cumulative incidences of relapse and non-relapse mortality. Transplanted patients are represented by blue and landmark controls by red.