Hematopoietic Cell Collection

Background

Bone marrow harvesting was the original process for HSC collection, which was first done in the 1960s. With the addition of umbilical cord blood and peripheral blood grafts, the use of bone marrow grafts declined. Despite this, bone marrow grafts still account for approximately 25% of graft sources for allogeneic hematopoietic cell transplantation ( Fig. 3.1 ).

Logistics

Bone marrow harvesting must be done in the operating room with the donor under general anesthesia, although regional anesthesia can be used in rare circumstances. Bone marrow is aspirated from the posterior iliac crests bilaterally. To limit peripheral blood hemodilution and increase HSC concentration, it is recommended to aspirate multiple small aliquots (<5 mL) totaling 15 to 20 mL per puncture site along with changes in needle position at short intervals. Also, using needles with multiple side holes, rather than a single hole, has been associated higher total nucleated cell (TNC) counts harvested. The National Marrow Donor Program (NMDP) guidelines recommend limiting the total amount of marrow collected to 20 mL/kg donor body weight. A TNC count midway into the procedure, typically after the first bag is collected, can help estimate the final TNC and limit unnecessary marrow collection. The bone marrow collected can then be infused unprocessed or processed, which includes red cell depletion for major ABO incompatibility, plasma depletion for minor ABO incompatibility, or volume reduction.

Some centers transfuse donors with autologous packed red blood cells during the bone marrow harvest. The World Marrow Donor Association (WMDA) and NMDP do not have specific recommendations regarding this practice. In a recent Center for International Blood and Marrow Transplant Research (CIBMTR) retrospective analysis regarding this practice, 4211 of the 7024 (60%) bone marrow donors received an autologous blood transfusion. In their analysis, donors who had a planned donation of ≥27% of the total blood volume were the most likely to benefit from transfusion with a slight decrease in fatigue and an increase in self-reported complete recovery by 5 days. It is worth noting that in this study, a total blood volume of ≥27% translated to 20 mL/kg, which is the maximal amount for collection recommended by the NMDP. In addition, donors who donate autologous blood need enough time for hematopoiesis to recover the volume lost. Therefore autologous blood transfusion during harvest may only be beneficial if large volume collection (≥ 27% of donor total blood volume) is planned and adequate time is given for red cell recovery.

Optimal Cell Dose

A formalized, standard cell dose from a bone marrow harvest has not been formally agreed upon by WMDA or NMDP. However, a cell dose of ≥ 2 × 10 ⁸ TNC/kg of recipient body weight has historically been accepted as a sufficient dose for engraftment. In recent years, most centers target a TNC dose of 3 to 5 × 10 ⁸ /kg recipient body weight because higher cell doses have been associated with better outcomes. While the data has been inconsistent because of various thresholds for TNC, a higher cell dose has been associated with faster neutrophil engraftment, better leukemia-free survival, lower relapse rates, lower nonrelapse mortality, and ultimately improved overall survival (OS). A cell dose < 2 × 10 ⁸ TNC/kg increases the risk for delayed engraftment and graft failure.

Donor characteristics have also been shown to influence the cell density from harvest. Factors associated with a higher cell dose include increased donor body weight, baseline leukocyte count, younger age, smoking history, hemoglobin level, and history of whole blood donation history within 1 year of donation.

Risk/Complications

Donor complications related to bone marrow collection are mild in general with more serious complications rarely occurring. The most common complaints after collection include pain at the collection site, throat pain from intubation, headache, and fatigue. All symptoms typically resolve within 1 month, although most report resolution of symptoms within a couple of days. A retrospective study by the NMDP reported serious medical complications following bone marrow collection in only 125 of 9245 donors (1.34%). These complications include mechanical injury (0.7%), anesthesia complications (0.5%), infection (0.01%), and seizure (0.01%). Multivariate analyses indicated that regional anesthesia, longer duration of collection, female sex, and older donor age were significant risks for serious complications.