Detectable minimal residual disease before hematopoietic cell transplantation is prognostic but does not preclude cure for children with very-high-risk leukemia

Abstract

In patients with acute leukemia, detection of minimal residual disease (MRD) before allogeneic hematopoietic cell transplantation (HCT) correlates with risk of relapse. However, the level of MRD that is most likely to preclude cure by HCT is unclear, and the benefit of further chemotherapy to reduce MRD before HCT is unknown. In 122 children with very-high-risk acute lymphoblastic leukemia (ALL; n = 64) or acute myeloid leukemia (AML, n = 58), higher MRD levels at the time of HCT predicted a poorer survival after HCT (P = .0019); MRD was an independent prognostic factor in a multivariate analysis (P = .0035). However, the increase in risk of death associated with a similar increment of MRD was greater in ALL than in AML, suggesting that a pretransplantation reduction of leukemia burden would have a higher impact in ALL. At any given MRD level, survival rates were higher for patients treated in recent protocols: the 5-year overall survival for patients with ALL was 49% if MRD was detectable and 88% if it was not and the corresponding rates for patients with AML were 67% and 80%, respectively. Although MRD before HCT is a strong prognostic factor, its impact has diminished and should not be regarded as a contraindication for HCT.

Figure 1

Survival and cumulative incidence of relapse after HCT stratified by MRD level. The survival (A) and relapse (B) probabilities were more favorable among patients with negative MRD than those with a low MRD level, who in turn fared better than patients with a high MRD level.

Figure 2

Survival probability based on the level of MRD stratified by treatment era. Probability of survival after HCT during the observation period among patients treated in the earlier era (red) and those in the recent era (blue). The confidence bands represent 95% CI limits. P < .0001 for recent versus earlier cohort and P = .0006 for MRD level.

Figure 3

Survival probability based on the level of MRD stratified by leukemia type and treatment era. Probability of survival during the observation period in patients with ALL (A) or AML (B) after HCT in the earlier era (red) or the recent cohorts (blue). The confidence bands represent 95% CI limits. Both ALL and AML patients treated in the recent era fared significantly better than those in the early era (P = .005 and P = .007, respectively). The impact of MRD level on survival was significant for ALL (P = .002) but not for AML (P = .18).