Detecting MRD During and After Hematopoietic Stem Cell Transplantation

Minimal residual disease (MRD) has the ability to predict which patients will relapse, and it also has a role regarding allogeneic hematopoietic cell transplantation (HCT), according 2 new studies presented at the Transplantation and Cellular Therapy Meetings of the American Society for Blood and Marrow Transplantation and Center for International Blood and Marrow Transplant Research.

The first study looked at whether detectable MRD before allogenic HCT was associated with different outcomes based on types of conditioning.¹ The study analyzed outcomes of 2780 patients with acute lymphoblastic leukemia (ALL). The authors explored if there were different outcomes in patients receiving myeloablative total body irradiation (TBI)—based or chemotherapy-based conditioning who had MRD detection before allogeneic HCT.

The patients had a median age of 38 years and underwent first HCT in complete remission between 2000 and 2017. MRD was detectable in 964 (34.6%) patients, and the other 1816 (65.3%) patients had no disease detectable before HCT. The majoriy of all patients (76%; n = 2122) received TBI-based conditioning.

The researchers found that MRD positivity was significantly associated with lower overall survival (OS) and leukemia-free survival (LFS) and a higher relapse incidence for the entire cohort of patients studied. In the TBI group, MRD detection was associated with lower OS and LFS and a higher relapse incidence. In the chemotherapy group, MRD positivity was only associated with a higher relapse incidence. TBI-based conditioning was associated with better OS, LFS, and relapse incidence in patients regardless of whether they were MRD positive or negative.

The second abstract evaluated the association of MRD with survival in patients with myelodysplastic syndrome (MDS) who received hematopoietic stem cell transplantation (HSCT). The researchers sampled peripheral blood mononuclear cells (PBMC) for 72 patients before they underwent HSCT. Before HSCT, 70% of cases had mutations with a variant allele frequency (VAF) of at least 10%, and they had an inferior overall survival compared with cases with less than 10% VAF.

The researchers analyzed mutations 30 days after HSCT and found 65% of patients still had detectable mutations. Disease-free survival and OS for patients with detectable mutations, who were considered MRD positive, were inferior to those of patients who were MRD negative. In the MRD-positive group, the 1-year relapse rate was 35%, compared with just 5% in the group of patients who were MRD negative.

MRD-positive patients with mutations detected at less 0.1% VAF had disease-free survival and OS that were as inferior as those of patients with mutations detected at 0.1% or greater, which suggests “ultrasensitive genomic MRD detection in peripheral blood identifies patients with very low level MRD at high risk for relapse and death post-HSCT,” the authors concluded.

References

1. Thompson L, Nazareno R, Clearwood A, et al. The role of measurable residual disease (MRD) at time of allogeneic hematopoietic cell transplantation in adults with acute lymphoblastic leukemia transplanted after myeloablative conditioning. a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Presented at: Transplantation and Cellular Therapy Meetings; February 20, 2019; Houston, TX. Abstract 7.
2. Pavlu J, Labopin M, Niittyvuopio R, et al. Ultrasensitive genomic minimal residual disease detection in peripheral blood after allogeneic HSCT for MDS is associated with increased relapse risk and inferior survival. Presented at: Transplantation and Cellular Therapy Meetings; February 20, 2019; Houston, TX. Abstract 171.