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, Apheresis or HPC(A)). Not included in these numbers are an estimated 200,000 newborn infants whose umbilical cord blood (HPC, Cord Blood) is collected and evaluated for potential storage in public cord blood banks and autologous HPC collections for medical therapies. Adverse reactions (AR) and serious adverse reactions (SAR) are not known to occur among cord blood donors, so they have been excluded from this report. Also excluded, are autologous HPC donations, even though such donations represent a much larger number of transplants. Nevertheless, reactions can be similar but patients are involved rather than healthy donors. In addition, regulatory issues are very different due to this practice.
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 apheresis . As a result, occasionally serious reactions such as arrhythmias, splenic rupture and vasculitis can occur. Common reactions include headache, bone pain, splenomegaly and thrombocytopenia. The collection process itself involves apheresis of the mononuclear cell components, which can have its own complications including central line thrombosis, citrate toxicity, hypotension, infection, leucopenia and thrombocytopenia. More severe reactions have also been reported including pulmonary embolism, subdural hematoma, sepsis and leukemia. In addition, reactions can be acute and immediate or chronic or delayed.
HPC(M) products are almost always collected in surgical suites with donors having received general or regional (epidural or spinal) anesthesia. Red cell transfusion with autologous or allogeneic products is common. 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 include bone and back pain, anemia, fever, headache and hypotension. More severe reactions including death have also been reported. These include stroke, air embolism, chest pain, endocarditis, fat embolism, iliac fracture and myeloproliferative diseases. Similarly, reactions can be acute or delayed.
Allogeneic HPC 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 . 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-tumor 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 AR among TC donors. The most common procedure for TC donation is unstimulated leukapheresis that is similar to apheresis 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 Serious Adverse Reactions (SARs) do occur and can be quite common, life threatening or fatal. SARs have been reported although they are rare and can be readily managed with symptomatic interventions. 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.
- Recommendations for reporting are largely based upon conclusions from the global donor follow-up conference held in Bern, Switzerland, in 2009.
- 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.
Life-threatening or fatal occurrences in the context of common donation-associated incidents should always be reported.
- 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.