Long-term follow-up of the EORTC-GINEMA AML-10 trial

The phase III randomized European Organization for Research and Treatment of Cancer-Gruppo Italiano Malattie Ematologiche dell’ Adulto (EORTC-GIMEMA) AML-10 trial assessed the impact of the type of induction and stem cell transplantation in younger patients with acute myeloid leukemia (AML).¹ The trial was amended to include a second randomization to compare autologous hematopoietic stem cell transplantation (auto-HSCT) with peripheral blood stem cells (APBSCT) and auto-HSCT with bone marrow (ABMT) in patients in first complete remission (CR) following intensive chemotherapy who did not have a human leukocyte antigen identical sibling donor available.²

Here, we summarize the long-term follow-up data from the second randomization of the EORTC-GIMEMA AML-10 trial published by Baron et al.² in American Journal of Hematology.

Study design and patient population²

• 292 patients were randomized to receive either APBSCT (n = 146) or ABMT (n = 146).
  • Among the patients randomized to receive APBSC, 104 received APBSCT, and 6 received ABMT.
  • Of the patients randomized to ABMT, 71 received ABMT, 17 received APBSCT, and 22 received ABMT followed by APBSCT rescue.
• The median age was 44 years (range, 15–60 years), and patient characteristics were comparable between treatment groups.
• While 22.3% of patients were not assessable, 19.9%, 51.4%, and 6.5% of patients were classified as favorable, intermediate, and adverse risk, respectively, according to the UK Medical Research Council classification.
• Median follow-up was 15.7 years and 16.0 years for the APBSCT and ABMT groups, respectively.

Key findings²

• The 5-, 10-, and 15-year disease-free survival (p = 0.48), cumulative incidences of relapse (p = 0.45), and overall survival (p = 0.52) rates from the second randomization were similar between treatment groups (Figure 1).

ABMT, autologous hematopoietic stem cell transplantation with bone marrow; APBSCT, autologous hematopoietic stem cell transplantation with peripheral blood stem cells; CIR, cumulative incidence of relapse; DFS, disease-free survival; OS, overall survival.
*Data from Baron, et al.²

• The 15-year disease-free survival, cumulative incidences of relapse, and overall survival rates among patients alive and still in first CR 5 years postrandomization were comparable between treatment arms Figure 2.

ABMT, autologous hematopoietic stem cell transplantation with bone marrow; APBSCT, autologous hematopoietic stem cell transplantation with peripheral blood stem cells; CIR, cumulative incidence of relapse; DFS, disease-free survival; OS, overall survival.
*Data from Baron, et al.²

• The 15-year cumulative incidence of death without relapse from randomization was 6.7% in the APBSCT group and 8.0% in the ABMT group.
• Multivariable analysis showed that cytogenetic adverse and intermediate risk, male sex, and higher CD43⁺ cell count (≥7×10⁶ CD34⁺ cells/kg) in the apheresis product were associated with worse survival outcomes (Table 1).

Table 1. Multivariable analysis for DFS, CIR, and OS in the AML-10 trial*

CI, confidence interval; CIR, cumulative incidence of relapse; DFS, disease-free survival; H, highest count of CD34+ cells ×106/kg body weight during a single apheresis; HR, hazard ratio; MRC, Medical Research Council; OS, overall survival. *Adapted from Baron, et al.2
Variable	DFS		CIR		OS
	HR (95% CI)	p value	HR (95% CI)	p value	HR (95% CI)	p value
MRC: Intermediate vs favorable	2.69 (1.63–4.45)	0.0001	2.63 (1.53–4.53)	0.0005	2.66 (1.55–4.58)	0.0004
MRC: Adverse vs favorable	5.90 (2.94–11.80)	<0.0001	7.02 (3.39–14.53)	<0.0001	6.98 (3.37–14.5)	<0.0001
Sex: male vs female	1.41 (1.04–1.91)	0.029	1.33 (0.96–1.85)	0.085	1.36 (0.98–1.88)	0.064
CD34 cell harvest: H ≥7 vs H <1	3.11 (1.64–5.87)	0.0005	4.48 (2.10–9.54)	0.0001	2.35 (1.24–4.44)	0.0086

 

Key learnings

Long-term outcomes were comparable between patients receiving APBSCT and ABMT. Among patients in first CR 5-years postrandomization, approximately 10–15% of patients died in the following 10 years, highlighting the need for long-term monitoring of patients who undergo auto-HSCT. Cytogenetic risk groups and CD34+ cell counts were predictive of long-term outcomes in this study.