Does younger donor age affect the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies beneficially?

Abstract

Sixty three patients aged 27-66 years (median 52) were allografted from HLA-matched sibling (n ¼ 47), 10 of 10 allele-matched unrelated (n ¼ 19), or one-antigen/allelemismatched (n ¼ 7) donors aged 24-69 years (median 46) after a conditioning regimen comprising 100 mg/m 2 melphalan. Cyclophosphamide (50 mg/kg) was also administered to patients who had not been autografted previously. Cyclosporine or tacrolimus, and mycophenolate mofetil were administered to prevent graft-versus-host disease (GVHD). The 2-year cumulative incidences of relapse and TRM were 55 and 24% respectively, and 2-year probabilities of overall survival (OS) and diseasefree survival (DFS) were 36 and 21%, respectively. Poor performance status, donor age 445 years and elevated lactate dehydrogenase (LDH) increased the risk of treatment-related mortality (TRM), refractory disease and donor age 445 years increased the risk of relapse, and OS and DFS were adversely influenced by refractory disease, poor performance status, increased LDH, and donor age 445 years. Our data suggest that younger donor age is associated with better outcome after submyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies due to lower TRM and relapse. This finding raises the question of whether a young 10-allele-matched unrelated donor is superior to an older matched sibling donor in patients where the clinical situation permits a choice between such donors.

Aging of registered stem cell donors: implications for donor recruitment

“…Differences are, however, not statistically significant. If new results showed that effects of donor age on transplantation success were smaller than demonstrated so far, [11][12][13][14] the preference of transplant physicians for younger donors could decline. As a result, both differences in age-specific donation probabilities and the number of donors who must be recruited to compensate for donor file aging would decrease.…”

“…Such preferences are in accordance with published results indicating more favorable transplantation outcomes for transplants that use younger donors. [11][12][13][14] The calculated donation probabilities provide the input for a model aimed to quantify the aging-induced reduction of donor file usefulness and to estimate the number R of donors who need to be recruited to compensate for this reduction. It shows that R exceeds the number of donors who reach the age limit considerably in both analyzed scenarios (intermediate typing of the HLA-A and -B loci versus more complete typing of new donors).…”

“…However, it may not be sufficient just to replace these donors to maintain the usefulness of a donor file since there is evidence that the outcome of hematopoietic stem cell transplantation is better for younger donors. [11][12][13][14] Therefore, even aging of those donors who are far below the age limit may lead to a decrease of donor file usefulness. We verify and quantify this effect and estimate the number of donors who have to be added annually to a given donor pool to compensate for this reduction in usefulness.…”

Pre-transplant prognostic factors of long-term survival after allogeneic peripheral blood stem cell transplantation with matched related/unrelated donors

“…[30][31][32][33][34][35][36] However, few studies have assessed the combined effect of donor age and type on outcome. Some studies have suggested more favorable outcome after transplant with young MUD as compared with older MRD.…”

Younger donor's age and upfront tandem are two independent prognostic factors for survival in multiple myeloma patients treated by tandem autologous-allogeneic stem cell transplantation: a retrospective study from the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC)

“…Donor's age has been previously studied in both myeloablative and non-myeloablative allogeneic transplant conditioning settings. 29,30 It has been hypothesized that as a donor's age increases, both repopulation and homing abilities of the donor stem cells become impaired. 31,32 Donor's T lymphocytes are also affected by telomere shortening and decreased effector activity.…”