CBF

(also see also see mesenchymal stem cells, transfusion, regulatory issues, autoimmune diseases, acute radiation injury, HIV positive patients)

 

vii. Adverse Events During Bone Marrow and PBSC Donation

  1. Adverse events among 2408 unrelated donors of peripheral blood stem cells: results of a prospective trial from the National Marrow Donor Program. Pulsipher MA, Chitphakdithai P, Miller JP, Logan BR, King RJ, Rizzo JD, Leitman SF, Anderlini P, Haagenson MD, Kurian S, Klein JP, Horowitz MM, Confer DL. Blood. 2009;113:3604-3611.

The authors report the results of a prospective trial describing donor adverse events (AEs) associated with filgrastim mobilized peripheral blood stem cell (PBSC) collections in 2408 unrelated volunteers.

Female donors had higher rates of AEs, requiring central line placement more often (17% vs 4%, P < .001), experiencing more apheresis-related AEs (20% vs 7%, P < .001), more bone pain (odds ratio [OR] = 1.49), and higher rates of grades II-IV and III-IV CALGB AEs (OR = 2.22 and 2.32). Obese donors experienced more bone pain (obese vs normal, OR = 1.73) and heavy donors had higher rates of Cancer and Leukemia Group B (CALGB) toxicities (> 95 kg vs < 70 kg, OR = 1.49). Six percent of donors experienced grade III-IV CALGB toxicities and 0.6% experienced toxicities that were considered serious and unexpected. Complete recovery is universal, however, and no late AEs attributable to donation have been identified.

The authors concluded that PBSC collection in unrelated donors is generally safe, but nearly all donors will experience bone pain, 1 in 4 will have significant headache, nausea, or citrate toxicity, and a small percentage will experience serious short-term adverse events. In addition, women and larger donors are at higher risk for donation-related AEs.

Prospective donors should be carefully educated about the measurable risk of significant acute toxicities they may encounter. Donors in this study did not experience the rare, filgrastim-related event of splenic rupture (incidence likely 1/5-10 000), and no donors experienced fatal complications (incidence worldwide estimated at 1/10,000).

In the setting of related donors, pediatric donors, and donors older than 60 years, the observations made in this study may not be valid. These donor groups have specific issues (size in pediatrics and increased risk of end-organ dysfunction and cancer in adults older than 60 years) that may put them at increased risk for toxicities associated with donation. Studies aimed at comprehensive assessment of early and late donation-related toxicities in related pediatric and adult donors, especially donors older than 60 years, are warranted.

  1. Severe events in donors after allogeneic hematopoietic stem cell donation. Halter J, Kodera Y, Ispizua AU, Greinix HT, Schmitz N, Favre G, Baldomero H, Niederwieser D, Apperley JF, Gratwohl A. Haematologica. 2009;94:94-101.

The risk for donors of allogeneic hematopoietic stem cells transplants is generally considered negligible. Scattered reports of severe complications and a recent controversy on hematopoietic malignancies after granulocyte colony-stimulating factor administration have challenged this opinion.

Three hundred and thirty-eight allogeneic transplant teams from 35 primarily European countries were asked to report numbers of fatalities, severe adverse events and hematologic malignancies occurring among their hematopoietic stem cell donors.

Two hundred and sixty-two of the 338 teams (77.5%) responded to a first survey (1993-2002) and 169 of the 262 responder teams (65%) to a second survey (2003-2005). They had performed a total of 51,024 first allogeneic hematopoietic stem cell transplantations, of which 27,770 were bone marrow and 23,254 peripheral blood.

They observed five donor fatalities, one after a bone marrow donation and four after peripheral blood donation (incidence 0.98 per 10,000 donations; 95% CI 0.32-2.29), 37 severe adverse events of which 12 were in bone marrow donors and 25 in peripheral blood donors.

Twenty donors developed hematologic malignancies, 8 were after donating bone marrow and 12 after donating peripheral blood stem cells. The observed incidence rate of hematologic malignancies did not exceed the expected incidence in an age- and sex-adjusted general population.

The authors concluded that hematopoietic stem cell donation is associated with a small but definite risk of fatalities and serious adverse events. True incidences might be higher, due to potential underreporting by study design. A continuous, standardized donor follow-up is needed to define donor risk groups and to monitor intermediate and long-term sequelae.

  1. Peripheral blood progenitor cell collection adverse events for childhood allogeneic donors: variables related to the collection and safety profile. Sevilla J, González-Vicent M, Lassaletta A, Ramírez M, Pérez-Martínez A, Madero L, Díaz MA. Br J Haematol. 2009;144:909-916.

Information related to adverse events (AE) in pediatric donors of peripheral blood progenitor cells (PBPC) and variables related to the collection is scanty. The authors analyzed 152 PBPC collections, and compared the complications and results between young children, older children and adults.

The pattern of AE was varied according to the age of the donor. Older pediatric donors and adults had a higher incidence of complaints related to PBPC priming (54.3% vs. 79.7%, respectively) than the youngest children (12%). On the other hand, these donors had a lower incidence of AE during PBPC collection (19.6% older children, 37.3% adults) mainly related to hypocalcaemia, than the youngest donors, who suffered mainly cardiovascular complications due to hypovolemia (51.7%).

The only variables related to collected cell dose were total blood volume processed per donor body weight, and CD34(+) cell count before apheresis. The donor/recipient body weight ratio predicted the outcome of collection in a single large volume leukapheresis. Donors with body weight ratio ≥ 0.75 had 4.69 times higher likelihood to reach the minimum target cell dose.