Patients ≥ 50 years old with leukemia/lymphoma are increasingly undergoing allogeneic hematopoietic cell transplants, raising questions about whether they might have better outcomes with transplants from younger allele-level 8/8 human leukocyte antigen (HLA)-matched unrelated donors than from HLA-matched siblings, who tend to be nearly as older than the patients themselves. “For older-age patients, use of a sibling donor, who usually is of a similar age to the patient, can be problematic due to the common presence of comorbidities as well as concerns regarding the regenerative potential of stem and immune cells from older donors,” noted authors of a study, published in the journal Blood, comparing outcomes for patients ≥ 50 who received hematopoietic cell transplants from matched sibling or matched unrelated donors.
A total of 1,415 patients received transplants from their siblings (median age 58, range 50-85 years) and 757 patients received transplants from unrelated donors (median age 34, range 19-49 years). The risks of acute and chronic graft-vs-host disease (GVHD) were higher after transplants from unrelated than from sibling donors. “The day-100 probability of acute grade 2-4 GVHD was higher at 46% (95% confidence interval [CI] = 43–50) after matched unrelated donor transplantation compared to 38% (95% CI = 35–40) after [matched sibling donor] transplantation (P < .001). The corresponding probabilities of acute grade 3-4 GVHD were 29% (95% CI = 26–32) after [matched unrelated donor] transplantation compared to 21% (95% CI = 19–23) after [matched sibling donor] transplantation (P < .001),” the investigators reported.
The 3-year probabilities of chronic graft-vs-host disease were 51% (95% CI = 46%–56%) after matched unrelated donor transplantation compared to 47% (95% CI = 43%–50%) after matched sibling donor transplantation (P = .12), the authors added. Multivariate analysis showed that chronic graft-vs-host disease was higher after matched unrelated donor transplantation compared to matched sibling donor transplantation, after adjusting for other significant factors associated with chronic graft-vs-host disease.
Performance scores affected risks of nonrelapse mortality and overall mortality. These risks were higher among patients with scores of 90 to 100 who received transplants from nonrelated than from matched sibling donors, but the risks were not significantly different for patients with lower performance scores. Relapse risks were also higher for those transplanted in relapse vs those in remission, and those who received reduced intensity compared to myeloablative regimens. Mortality, treatment failure, and relapse risks were lower for patients with chronic lymphocytic leukemia, compared to acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, chronic myeloid leukemia, and non-Hodgkin lymphoma.
“As patient age is correlated with donor age in the group of patients who received [matched sibling donor] transplants, we explored for a donor age cut-off in this population; after adjusting for performance score, conditioning regimen, disease, and disease status, overall mortality risks were higher in patients who received grafts from their siblings aged 67 years or older compared to those who received grafts from siblings aged 50–66 years [hazard ratio (HR) = 1.47, 95% CI = 1.19–.82, P < .001],” the investigators reported. “Relapse risks but not [graft-vs-host disease or nonrelapse mortality] were also higher in patients who received grafts from their siblings aged 67 years or older compared to those who received grafts from younger siblings [HR = 1.55, 95% CI = 1.18–2.05, P = .002]. Among unrelated donors we did not identify an age cut-point associated with survival,” the authors noted.
They concluded: “When selecting a donor for patients who are 50 years or older with performance scores of 90 or 100, priority should be for a sibling donor aged less than 67 years than a younger-aged [matched unrelated donor]. Similarly, for patients with lower performance scores and/or when the donor is 67 years or older,” lower acute and chronic graft-vs-host-disease rates after matched sibling donor compared to matched unrelated donor transplantation favor a matched sibling donor when available. ■
Alousi AM, et al: Blood, January 29, 2013 (early release online).