MRD status as a predictor of survival outcomes in patients with ALL undergoing allo-HSCT in CR2 or later

In patients with acute lymphoblastic leukemia (ALL), measurable residual disease (MRD) status has been demonstrated as a useful predictor of survival outcomes.¹ Currently, the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines recommend that allogeneic hematopoietic stem cell transplant (allo-HSCT) is carried out in patients with high-risk ALL within the first complete remission (CR); however, for some patients, allo-HSCT may be deferred to a later stage despite the challenges of maintaining a second CR with allo-HSCT consolidation. The ALL Hub has previously reported an expert opinion on how MRD can guide therapeutic decisions in ALL. Here, we summarize a recent article by Pasvolsky et al.¹ examining the prognostic significance of MRD status in patients with ALL undergoing allo-HSCT later than first CR, recently published in Am J Hematol.

Study design

This study enrolled 162 adult and pediatric patients with ALL (B-cell ALL, n = 123; T-cell ALL, n = 39) who underwent allo-HSCT in second CR or later between 2004 and 2021 at the MD Anderson Cancer Center, US. The primary endpoint was cumulative incidence of leukemia relapse, with secondary endpoints including overall survival (OS), progression-free survival (PFS), and non-relapse mortality. Patients were evaluated for their MRD status pretransplant.

Results

Baseline patient characteristics at time of transplant are shown in Table 1.

Table 1. Baseline patient characteristics*

Median follow-up was 51 months in patients who survived (n = 74). Differences in PFS and OS for MRD-positive and MRD-negative patients are shown in Figure 1.

Figure 1. Outcomes in the surviving patients* 

MRD, measurable residual disease; OS, overall survival; PFS, progression-free survival.
*Adapted from Pasvolsky, et al.¹

A total of 88 patients died during the study and the primary cause was leukemia progression; causes of death are reported in Table 2. Leukemia progression affected a higher proportion of MRD-positive patients compared with MRD-negative patients.

Table 2. Causes of death*

Impact of MRD status on disease progression

In univariate analysis, pretransplant MRD positivity was associated with reduced OS and an increased relapse rate; ≥2 prior lines of therapy and any conditioning regimen other than total body irradiation was also associated with an increased risk of relapse. Patients who received a transplant in third CR or later had a significantly increased risk of non-relapse mortality and worse OS.

Multivariate analysis showed a similar association between pretransplant MRD positivity and increased rate of relapse, reduced OS, and worse PFS. In patients who received a transplant in their third CR or beyond, MRD status was not found to be associated with relapse risk.

Conclusion

This study demonstrated that in patients with ALL undergoing allo-HSCT in second CR or beyond, pretransplant MRD positivity is a key predictor of disease relapse, PFS, and OS.