Through the recruitment of immunologic mechanisms, allogeneic hematopoeitic cell transplantation (HCT) has been establiched as a curative treatment for various hematologic diseases. The most convenient source to obtain hematopoietic progenitor cells are peripheral blood stem cells (PBSCs) which are harvested from the donor via leukapheresis after mobilization with granulocyte-colony stimulating factors. With the introduction of reduced intensity condition (RIC), the curative potential of allogeneic HCT became accessible to older and/or frail patients otherwise
ineligible for HCT. However, new challenges arise as the increasing age of patients is inevitably accompanied by a comparable increase in the age of donors. Safety considerations of collecting PBSCs might attain new dimensions. Data to potential risks in elderly donors are lacking. Moreover, the impact of donor’s age on the feasibility of PBSCs collection and on the quality of the harvest in terms of stem cells (CD34+) and natural killer (NK)-cells has not been studied. It is also unknown whether PBSCs obtained from donors above 50 years would negatively influence engraftment or the incidence of graft-versus-host disease (GVHD) in the recipient.
These questions were explored in a retrospective study including 167 recipients of an allogeneic HCT (52.7% after RIC) from a matched related sibling. Median donors’ age was 47 years [67 (40%) donors were > 50 years including 34 donors > 60 years]. Safety of mobilization and leukapheresis was age independent. Adequate PBSCs were collected from all donors though a higher CD34+-cell count was seen in donors
< 50 years (p<0.0005), whereas harvests from donors > 60 years contained a higher NK-cell count (p=0.003). Engraftment in the recipient occurred after a median of 12 days and was not affected by an advanced donor age. Similarly, a higher incidence of GVHD was not seen in recipients of harvests from older donors. For the first time, we show that donor’s age, even beyond 60 years, does not preclude successful collection of PBSCs from siblings, does not jeopardize the short-term safety of the
donor, and is not associated with deleterious sequels for the recipient in terms of engraftment or GVHD. As NK-cells have been implicated in the suppression of GVHD, and the mediation of a graft versus leukemia effect, the impact of the higher number of NK-cells in harvests from elderly donors on relapse of hematologic malignancies in the recipient warrants further studies.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa.de:bsz:15-qucosa-171123 |
| Date | 15 July 2015 |
| Creators | Al-Ali, Haifa Kathrin |
| Contributors | Universitätsklinikum Leipzig AöR,, Christoph Baerwald, Thomas Berg |
| Publisher | Universitätsbibliothek Leipzig |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | doc-type:doctoralThesis |
| Format | application/pdf |
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