[Collection of hematopoietic progenitor cells from healthy donors]

Allogeneic hematopoietic progenitor cell (HPC) transplantation is an established therapy for many hematologic disorders. HPCs may be collected from bone marrow, peripheral blood, or umbilical cord blood. In order to minimize the risk for healthy HPC donors, thorough investigation is required before donation. The donor work-up should include medical history, physical examination, ECG, chest x-ray, blood count, coagulation screening, and testing for infectious disease markers. Donors should be fully informed on the donation procedure and sign an informed consent for donation. HPCs are traditionally collected from bone marrow with the donor in general anesthesia. The procedure includes multiple bone marrow aspirates from pelvic bones and at least overnight hospital stay. Although marrow donation is generally safe and well tolerated, minor complications like pain at the collection site, fatigue and pain on walking or sitting may occur in a relatively small proportion of donors (6%-20%). Major and life-threatening complications such as anesthesia-related events, mechanical injury to the bone, sacroiliac joint and sciatic nerve following marrow donation are relatively rare, being estimated to 0.1%-0.3% of cases. In the last decade, peripheral blood progenitor cells (PBPC) have become an increasingly used altemative to bone marrow. PBPC transplantation offers faster hematopoietic recovery and lower early transplant-related morbidity and mortality. The incidence of acute graft vs. host disease (GvHD) is no greater than in bone marrow transplants. However, there is evidence for increased chronic GvHD, which is in part related to the higher number of T and NK cells that are collected with PBPC and re-infused to the patient. Recombinant human granulocyte colony-stimulating factor (G-CSF) is used to mobilize PBPCs for collection by leukapheresis. Leukapheresis is usually perfomed after 4 to 5 days of G-CSF subcutaneous administration at a dose of 10 mg/kg b.w. Vascular access for apheresis may be accomplished by use of apheresis needle in antecubital vein. Placement of a double-lumen central apheresis catheter is rarely required in healthy donors. Citrate is the most commonly used anticoagulant for apheresis. One to three leukapheresis procedures are required to collect adequate graft. There is an interindividual variation in progenitor cell mobilization among healthy donors, with a subset of donors that do not exhibit effective CD34+ cell mobilization. Donor age and G-CSF schedule are the factors that significantly affect PBPC mobilization and collection in healthy donors. Procedures for mobilization and collection of PBPC from healthy donors are generally well tolerated. Common adverse reactions of G-CSF application include bone pain, myalgia, headache and fatigue. Beside these mild side effects, moderate to life-threatening complications are sporadically observed. Spontaneous splenic rupture, acute lung injury, acute iritis, severe pyogenic infections, and anaphylactoid reactions were reported in healthy donors after G-CSF administration. Adverse effects of apheresis for PBPC collection are the same as for other apheresis procedure and include complications related to venous access and citrate toxicity. Leukapheresis typically results in a lower platelet count, an effect that is exacerbated by the use of G-CSF, which has been documented to cause mild, reversible thrombocytopenia. Fewer side effects were noted in pediatric donors compared to adult donors. PBPC collection in pediatric donors is safe and desired PBPC yields are easily achieved. Theoretical concerns exist about the potentially increasing long-term risk of leukemia after G-CSF administration in healthy donors. Recently, a report of AML developing in a 62-year-old female donor 14 months after G-CSF-primed PBPC donation has been published. Whether G-CSF therapy contributed to the development of this cancer is unknown, but future studies should carefully follow the donors and report any similar event. According to currently available evidence, the risk of major late toxicities secondary to administration of G-CSF is minimal.