Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age

Abstract

The National Marrow Donor Program (NMDP) maintains a registry of approximately 4 million volunteer unrelated donors for patients in need of a stem cell transplant. When several comparably HLA-matched volunteers are identified for a patient, various criteria are used to select a donor. A retrospective analysis of 6978 bone marrow transplantations facilitated by the NMDP from 1987 to 1999 was conducted to study the effects of various donor characteristics on recipient outcome. The evaluation addressed possible effects of donor age, cytomegalovirus serologic status, ABO compatibility, race, sex, and parity on overall and diseasefree survival, acute and chronic graftversus-host disease (GVHD), engraftment, and relapse. Age was the only donor trait significantly associated with overall and disease-free survival. Fiveyear overall survival rates for recipients were 33%, 29%, and 25%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P ‫؍‬ .0002). A similar effect was observed among HLA-mismatched cases (28%, 22%, and 19%, respectively). A race mismatch between recipient and donor did not affect outcome. The cumulative incidences of grade III or IV acute GVHD were 30%, 34%, and 34%, respectively, with donors aged 18 to 30 years, 31 to 45 years, and more than 45 years (P ‫؍‬ .005). The corresponding incidences of chronic GVHD at 2 years were 44%, 48%, and 49% (P ‫؍‬ 0.02). Recipients with female donors who had undergone multiple pregnancies had a higher rate of chronic GVHD than recipients with male donors (54% versus 44%; P < .0001). The use of younger donors may lower the incidence of GVHD and improve survival after bone marrow transplantation. Age should be considered when selecting among comparably HLA-

Cell intrinsic and extrinsic mechanisms of stem cell aging depend on telomere status

“…Telomere shortening and declined repopulating capacity with increasing donor age (Widmann et al,2008;Castro-Malaspina et al, 2002;Kollman et al, 2001Yakoub-Agha et al,2006. Cell extrinsic: Long-term survival of bone marrow transpanted patients is significantly reduced in older recipients.…”

“…In humans, it has been shown that both donor age (Castro-Malaspina et al, 2002;Kollman et al, 2001) and recipient age (Kantarjian et al, 2006;Socie et al, 1999) influence patients' outcomes in response to hematopoietic stem cell (HSC) transplantation. These clinical data indicate that cell intrinsic and cell extrinsic (environmental) mechanisms could contribute to the functional decline of HSCs during human aging.…”

Age-Dependent Depletion of Human Skin-Derived Progenitor Cells

“…To our knowledge, evidence for stem/progenitor cell pool depletion in the human body with aging includes peripheral blood stem cells [8,9], satellite cells of skeletal muscle [10], and putative stem cells of the epidermal compartment of the skin [11]. Interestingly, in a retrospective analysis of >6,900 bone marrow transplantations conducted by the National Marrow Donor Program, age was the only donor trait significantly associated with recipient survival [12]. On the other hand, donor age does not apparently affect phenotype of human corneal epithelial cells…”

Strategies of the donor search for children with second CR ALL lacking a matched sibling donor

“…27 These results were not confirmed by a recent study that detected no adverse effects of donor and recipient CMV serology status on survival, GvHD, engraftment or relapse. 31 The preemptive use of drugs such as ganciclovir and CMV-specific T cells might contribute to preventing CMV infections in recipients who are at risk.…”

“…In a large, single-centre study, multivariate analysis showed that donor age plays a more important role in better survival and in better disease-free survival 31 than donor CMV serology status, gender, parity, ABO incompatibility and race. This might be due to the fact that there is greater replacement of naive T cells by memory T cells as age increases, thus leading to decreased tolerance, as the immune system is exposed to a greater variety of foreign Ags 32 or to decreased marrow cellularity over time.…”