Living donors provide an estimated 25-30,000 HPC products annually for use in related- and unrelated-donor allogeneic hematopoietic cell transplantation (HCT). These are donations of bone marrow (HPC, Marrow or HPC(M)) and peripheral blood stem cells (HPC, Aphaeresis or HPC(A)). Not included in these numbers are an estimated 200,000 new-born infants whose umbilical cord blood (UCB) is collected and evaluated for potential storage in public cord blood banks and autologous HPC collections for medical therapies.
Today, HPC(M) donations from children and adults are much less frequent than HPC(A) donations, which comprise about 80% of the total. Preparation for HPC(A) donation almost always involves mobilization of HPC from the bone marrow space into the peripheral blood stream through administration of a mobilization agent. Most often the mobilizing agents are filgrastim or lenograstim administered subcutaneously, once or twice daily for 4 to 5 days prior to aphaeresis (19). As a result:
- Common reactions include headache, bone pain, splenomegaly and thrombocytopenia.
- Occasionally serious reactions such as arrhythmias, splenic rupture and vascular problems can occur.
The collection process itself involves apheresis of the mononuclear cell components, which can have its own complications (acute, immediate or chronic or delayed) including:
- Central line thrombosis, citrate toxicity, hypotension, infection, mild leucopenia and thrombocytopenia (unassociated with clinical complaints).
- More severe reactions have also been reported including pulmonary embolism, subdural hematoma, sepsis
HPC(M) products are almost always collected in surgical suites with donors having received general or regional (epidural or spinal) anaesthesia. Red cell transfusion with autologous is common (transfusion with allogeneic products is rare and classed an adverse event). In some countries the standard of care for HPC(M) donors is hospitalization for 1 or 2 days, but in many others “day surgery” without overnight hospitalization is the usual practice. Common reactions (acute or delayed) include
- Bone and back pain, anemia, fever, headache and hypotension.
- More severe reactions (including death which is very rare) have also very rarely been reported. These include stroke, air embolism, chest pain, endocarditis, fat embolism, iliac fracture and
Allogeneic HPC(M) donations by children are common in the related donor setting. The use of children as HPC donors has been the subject of ethical discussions and occasional controversies (20). The wisdom and safety of HPC(A) donation by children has been debated, but it appears these donations are safe.
Therapeutic cells (TC) are cells collected from a donor that are not intended for HCT, per se. These include cells such as unfractionated mononuclear cells, T lymphocytes, antigen-presenting cells, mesenchymal cells, et cetera. TC are employed, for example, for immunomodulation, immune reconstitution, tissue repair, anti-viral treatment and anti-tumour therapy. Most often allogeneic TC donors are also HPC donors providing additional products for their recipients, but donations of TC that are not coupled to HPC donation appear to be increasing.
There are few data on adverse reactions among TC donors. The most common procedure for TC donation is unstimulated leukapheresis that is similar to aphaeresis procedures for platelet or red cell donation. Considerable information exists on the risks of these unstimulated apheresis procedures.
HPC donation is most often a safe procedure but harm can occur to donors and short-term mild side effects can be quite common. Cases of life threatening or fatal harm have been reported although they are rare. In long-term follow-up, new-onset cancers and autoimmune disorders are encountered, but there is currently no evidence that these occur at higher-than-expected rates then the general public.
Recommendations:
1. Recommendations for reporting are largely based upon conclusions from the global donor follow-up conference held in Bern, Switzerland, in 2009.
2. Adverse occurrences at any time between initiation of the donation procedure and 30 days after completion of the collection should be reported. Reporting of hospitalization-related occurrences that result from common donation-associated incidents, e.g., nausea, vomiting, pain, headache, may be excessive because the distinction between adverse occurrences and hospital-related incidents in these cases is highly dependent upon geographical differences, practice standards, and regulatory requirements and may not need to be reported. Life-threatening or fatal occurrences in the context of common donation-associated incidents should always be reported.
3. A mechanism for long-term follow-up of HPC donors is recommended on an annual or biannual basis for at least 10 years. At a minimum, donors should be contacted at 1, 5 and 10 years following completion of donation. The assessment should include survival, and if not surviving, a cause of death; new onset of hematologic or non-hematologic malignancy and new onset of autoimmune disease. Diagnoses should be specified by ICD codes.