Impact of MRD status in patients with AML undergoing allogeneic stem cell transplantation in the first vs the second remission

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) offers the best chance for relapse-free survival to most patients with acute myeloid leukemia (AML). It may be performed during complete remission or delayed until after the first relapse because of relevant treatment-related morbidity and mortality. The measurable residual disease (MRD) status at HSCT adds refined prognostic information to the assigned European LeukemiaNet (ELN) 2017 genetic risk at diagnosis. We analyzed 580 patients with AML who underwent allogeneic HSCT during either the first (79%) or second (21%) remission. Although, because of common treatment strategies, some adverse risk characteristics, such as monosomal or complex karyotypes, were less frequent in patients who underwent transplant in the second remission, those patients had worse outcomes compared with patients who had transplant in the first remission. The MRD status at HSCT was an independent prognostic factor, irrespective of the number of remissions at HSCT. Notably, patients who were MRD+ who underwent HSCT in the first remission and those who were MRD- and underwent transplant in the second remission had similar outcomes. In the clinically highly relevant group of individuals who had ELN2017 intermediate risk, the MRD status provided the highest prognostic value with very dismal outcomes for patients who were MRD+ and underwent second-remission transplants. The adverse outcomes of patients who are MRD+ and of those who undergo transplant in the second remission should be considered when planning consolidation treatment, to avert an allogeneic HSCT in MRD+ second remission when possible.

Graphical abstract

Figure 1

Outcomes of patients with AML according to the number of CRs/CRis (first vs second) at allogeneic HSCT (n = 580). (A) CIR, (B) NRM, (C) RDS, and (D) OS.

Figure 2

Outcomes of patients with AML according to the number of CRs/CRis (first vs second) and the MRD status at allogeneic HSCT (positive vs negative; n = 300). (A) CIR. MRD⁺ vs MRD⁻: first CR/CRi (P < .001) and second CR/CRi (P < .001). (B) RFS. MRD⁺ vs MRD⁻ first CR/CRi (P = .002) and second CR/CRi (P = .04). (C) OS. MRD⁺ vs MRD⁻: first CR/Cri (P = .07) and second CR/Cri (P > .99).

Figure 3

Distribution and outcomes of patients that underwent allogeneic HSCT during first or second remission according to the ELN2017 genetic risk groups. (A) Distribution of the ELN2017 risk groups of patients who underwent allogeneic HSCT during the first or second CR/CRi. (B-D) CIR in patients with AML according to the number of CRs/CRis (first vs second) at allogeneic HSCT in the 3 ELN2017 genetic risk groups. ELN2017 favorable risk (B; n = 112), ELN2017 intermediate risk (C; n = 147), and ELN2017 adverse risk (D; n = 158). (E-G) Cumulative incidences of relapse of patients with AML according to the number of CRs/CRis (first vs second) and the MRD status at allogeneic HSCT (positive vs negative) in the 3 ELN2017 genetic risk groups. (E) ELN2017 favorable risk (n = 80), MRD⁺ vs MRD⁻: first CR/CRi (P = .21) and second CR/CRi (P = .003). (F) ELN2017 intermediate risk (n = 77), MRD⁺ vs MRD⁻: first CR/CRi (P = .02) and second CR/CRi (P = .002). (G) ELN2017 adverse risk (n = 83), MRD⁺ vs MRD-⁻: first CR/CRi (P = .06) and second CR/CRi (P = .81).