Haplo-HCT From Older Donors Associated With Worse Outcomes in Acute Leukemias

The use of haploidentical (haplo) related donors has made it possible for patients with leukemia who lack a human leukocyte antigen (HLA)–matched donor to receive a hematopoietic cell transplantation (HCT). But, because several haplo relative donors are typically available for any given patient, choosing the “best” donor for a patient is complicated.

According to a retrospective study presented at the 2017 ASH Annual Meeting, older donor age appears to lead to worse post-HCT survival outcomes, including higher non-relapse mortality (NRM) and shorter overall survival (OS). Patients who received transplants from their adult children (older than 35 years) also had worse outcomes, reported lead author Jonathan Canaani, MD, of the Hematology Division at the Sheba Medical Center in Givatayim, Israel.

Researchers retrospectively analyzed the multinational registry of the European Society for Blood and Marrow Transplantation’s Acute Leukemia Working Party to identify patients with acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) who underwent a first haplo-HCT between 2005 and 2015. Of the 1,270 patients included, 1,019 had AML and 251 had ALL. Most patients (n=700) were 40 years or older when they received haplo-HCT, and the remaining 570 patients were younger than 40.

After a median follow-up of 27 months (range = 0.6-119 months), results from multivariate analyses revealed that, among patients older than 40 years, outcomes were worse when donors were older than 40 years, compared with donors younger than 40. In addition to higher NRM (hazard ratio [HR] = 1.86; 95% CI 1.18-2.94; p=0.007), older donor age was associated with inferior:

  • leukemia-free survival (LFS): HR=1.59 (95% CI 1.13-2.24; p=0.007)
  • OS: HR=1.74 (95% CI 1.22-2.47; p=0.002)
  • graft-versus-host-disease (GVHD)–free or relapse-free survival (GRFS): HR=1.6 (95% CI 1.16-2.22; p=0.004)

Donor relationship to patients (sibling vs. child donor) did not statistically significantly impact outcomes, the researchers reported. However, in the group of patients over 40 years who received transplants from their children, outcomes were less favorable when donors were over the age of 35. These recipients experienced an increased rate of NRM (HR=1.82; 95% CI 1.13-2.9; p=0.01), inferior LFS (HR=1.5; 95% CI 1.05-2.13; p=0.03), and inferior OS (HR=1.5; 95% CI 1.04-2.15; p=0.03), compared with recipients who had younger donors.

The effect of donor age was less straightforward in younger recipients (<40 years). In this group, having a donor older than 55 years was independently associated with a lower risk for extensive chronic GVHD (HR=0.16; 95% CI 0.02-0.95; p=0.044), but an increased risk of relapse (HR=1.85; 95% CI 0.97-3.49; p=0.058). The rates of NRM, OS, LFS, acute GVHD, and GRFS were not statistically significantly impacted by donor age in those younger than 40 years.

“Our data establish donor age and kinship as significant determinants of outcome following haplo-HCT for [patients with] acute leukemia,” the authors concluded, “with potential implications for future donor selection algorithms in haplo-HCT.”

The findings of the study were limited by its retrospective nature, and other studies are needed to confirm the results and determine the underlying factors that might contribute to poorer post-HCT survival with older donors.

The authors report financial relationships with Celgene, Novartis, Jazz Pharmaceuticals, Bristol-Myers Squibb, and Janssen.


Reference

Canaani J, Savani BN, Labopin M, et al. Donor age determines outcome in acute leukemia patients undergoing haploidentical hematopoietic cell transplantation. Abstract #850. Presented at the 2017 American Society of Hematology Annual Meeting, December 11, 2017; Atlanta, GA.

 

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