Prognostic Significance of Post-Transplant MRD Varies Based on Conditioning Regimen in ALL

Assessment of measurable residual disease (MRD) prior to allogeneic hematopoietic cell transplantation (alloHCT) is an established important prognostic factor in patients with acute lymphocytic leukemia (ALL). According to results from a retrospective study, the presence of MRD after alloHCT also has prognostic value, and the significance of MRD differs depending on the type of conditioning regimen.

Jiri Pavlu, MD, from Imperial College at Hammersmith Hospital in London, presented the findings at the 2019 Transplantation & Cellular Therapy (TCT) Meetings of ASBMT and CIBMTR.

“In this large study, we confirmed that patients who are MRD-negative prior to alloHCT achieve superior outcomes,” Dr. Pavlu reported. “This was particularly apparent if total-body irradiation conditioning was used.”

Attendees view presentations at the 2019 TCT Meetings.

The researchers conducted this retrospective multicenter study to explore whether the prevalence of post-alloHCT MRD differed when a patient underwent conditioning with total-body irradiation versus chemotherapy. They analyzed outcomes from 2,780 patients (median age = 38 years; range = 18-72 years) who underwent a first alloHCT in complete remission between 2000 and 2017. All participants had alloHCT with a sibling or unrelated 9/10 or 10/10 human leukocyte antigen (HLA)-matched donor.

Before alloHCT, 1,816 patients (65.3%) had no detectable disease (MRD-negativity) and 964 patients (34.7%) were MRD-positive. Most patients (n=2,122; 76%) underwent conditioning with total-body irradiation.

In the entire cohort, the authors observed that MRD-positive status pre-alloHCT was an independent predictor for poorer survival and higher risk of relapse (p values not reported):

  • hazard ratio (HR) for overall survival (OS): 1.19 (95% CI 1.02-1.39)
  • HR for leukemia-free survival (LFS): 1.26 (95% CI 1.1-1.44)
  • HR for relapse incidence (RI): 1.51 (95% CI 1.26-1.8)

When the researchers examined the relationship between MRD and conditioning regimen, they found that, in the total-body irradiation cohort, MRD-positivity before alloHCT was associated with lower OS and LFS, but higher RI:

  • HR for OS: 1.26 (95% CI 1.05-1.51)
  • HR for LFS: 1.3 (95% CI 1.1-1.53)
  • HR for RI: 1.53 (95% CI 1.23-1.9)

In the chemotherapy-based conditioning cohort, however, only the risk of relapse was higher among MRD-positive patients (HR=1.58; 95% 1.13-2.21).

“Total-body irradiation–based conditioning was associated with improved OS, LFS, and RI in both MRD-negative and MRD-positive patients,” the authors concluded. Based on these findings, they wrote that “all patients with ALL, irrespective of MRD status [before alloHCT], benefit from total-body irradiation–based conditioning in the myeloablative setting.”

The authors report no relevant conflicts of interest.

Reference

Pavlu J, Labopin M, Niittyyuopio R, 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. Abstract #7. Presented at the Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR, February 20, 2019; Houston, TX.

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