iii. STRATEGIES FOR CORD BLOOD COLLECTION

1. A modified cord blood collection method achieves sufficient cell levels for transplantation in most adult patients. Bornstein R, Flores AI, Montalban MA, del Rey MJ, de la Serna J, Gilsanz F. Stem Cells. 2005;23:324-34.

To increase the yield in umbilical cord blood (UCB) collection the authors designed a modified placental/umbilical two-step collection method in which a standard blood fraction obtained by umbilical venipuncture is combined with a second fraction harvested after placental perfusion with 50 ml heparinized 0.9% saline. This second fraction contributed 32% volume and 15% to the nucleated cells (NCs) to the whole UCB unit (123.7 ± 50.1 ml and 1.26 ± 0.52 x 10⁹ NCs). The proportion of progenitor cells in both fractions was not significantly different, indicating that the hematopoietic potential of these larger units is 20% (range, 2%-100%) higher than UCB units collected by standard methods. In addition, the bacterial contamination rate associated with this novel collection method (2.78%) compares favorably.

Since 1998 the authors have further enriched their units by processing only those containing over 0.8 x 10⁹ NCs, resulting in a 36% cell increment (1.46 +/- 0.52 x 10⁹ NCs). Thus, 84% and 54% of the Madrid UCB Bank inventory would fulfill the target cell dose of 2 x 10⁷/kg in patients weighing 50 and 65 kg, respectively. This significant UCB banking improvement gives larger pediatric and adult patients a greater chance of finding adequate grafts in order to achieve better clinical outcomes after UCBT.

2. In utero or ex utero cord blood collection: which is better? Lasky LC, Lane TA, Miller JP, Lindgren B, Patterson HA, Haley NR et al. Transf 2002; 42:1261-1267.

This study compared two collection methods to assess cord blood content, including cell numbers. One method utilized trained obstetricians and midwives to collect cord blood in utero before the delivery of the placenta. The other method use personnel who collected cord blood ex utero after the delivery of the placenta. The authors concluded that cord blood can be collected successfully using either method with comparable nucleated cell, MNC, CD34+, and CFU-GM numbers.

3. Influence of mode of birth and collection on WBC yields of umbilical cord blood units. Sparrow RL, Cauchi JA, Ramadi LT, Waugh CM, Kirkland MA. Transf 2002; 42:210-215.

No significant differences were found in cord bloods collected in utero (n = 58) vs. ex utero (n = 99). The authors did find that the volume of CB was higher following caesarean section than vaginal delivery but cord bloods from vaginal delivery had a significantly higher WBC concentration. As a consequence of the opposing effects on volume and WBC counts, there were no significant differences in the total number of WBCs or CD34+ cells related to the mode of delivery.

4. Comparison between two strategies for umbilical cord blood collection. Solves P, Moraga R, Saucedo E, Perales A, Soler MA, Larrea L et al. Bone Marrow Transplant 2003; 31:269-273.
Comparison between two cord blood collection strategies. Solves P, Mirabet V, Larrea L, Moraga R, Planelles D, Saucedo E et al. Acta Obstet Gynecol Scand 2003; 82:439-442.
In utero or ex utero cord blood collection: an unresolved question. Solves P, Moraga R, Mirabet V, Larrea L, Soler MA.Transf 2003; 43:1174-1176.

In contrast to the previous cited studies, these investigators concluded that the in utero collection method is optimal. A larger number volume and a higher number of nucleated cells, percentage of CD34+ cells and colony-forming units were harvested by in utero collection. The authors cite two other studies with similar conclusions (Surbek et al BMT 1998;22:311-312 and Wong et al BMT 2001;27:133-138). Caesarean deliveries contained similar progenitor content to vaginal deliveries.

5. In utero or ex utero cord blood collection: an unresolved question. Lasky LC, Haley NR, Ballen KK. Transf 2003; 43:1176.

A commentary on the pros and cons of the two collection methods concluded that both methods can result in safe and effective cord blood collection.

6. Obstetric predictors of placental/umbilical cord blood volume for transplantation. Jones J, Stevens CE, Rubinstein P, Robertazzi RR, Kerr A, Cabbad MF. Am J Obstet Gynecol 2003; 188:503-509.

The authors documented that the volume of residual placental cord blood that is collected for hematopoetic stem cell transplantation can be improved when a longer length of the cord is left with the placenta and when there is a shorter time between the delivery of the placenta and the collection.

7. Bigger is better: maternal and neonatal predictors of hematopoietic potential of umbilical cord blood units. Ballen KK, Wilson M, Wuu J, Ceredona AM, Hsieh C, Stewart FM et al. Bone Marrow Transplant 2001; 27:7-14.

The authors determined whether maternal factors have an effect on laboratory parameters of hematopoietic potential, such as viability, cell counts, CD34+ cell counts, and CFU-GM. They found, in multivariate analysis, that babies of longer gestational age had higher cell counts, but lower CD34+ cell counts and CFU-GM. Bigger babies had higher cell counts, more CD34+ cells, and more CFU-GM. Women with fewer previous live births also produced cord units with higher cell counts, CFU-GM, and CD34+ cell counts. These data may be used to select the optimal cord blood donors and allow cord blood banks efficient resource allocation.

8. Red blood cell depletion with a semiautomated system or hydroxyethyl starch sedimentation for routine cord blood banking: a comparative study. Solves P, Mirabet V, Planelles D, Blasco I, Perales A, Carbonell-Uberos F, Soler MA, Roig R. Transfusion. 2005;45:867-73.

The authors point out that the major problem with long-term cord blood (CB) banking is the required storage space. A major concern of CB banking is the limited storage space available in nitrogen tanks. For this reason, many studies have been performed to establish techniques for volume reduction of CB units.

The authors compared two different methods for CB volume reduction in both development and routine phases: hydroxyethyl starch (HES) sedimentation and top-and-bottom fractionation with the Optipress II (Baxter Healthcare). Monitoring the total nucleated cell (TNC) count, lymphocytes, CD34+ cells, and colony-forming unit (CFU) content in both preprocess and postprocess CB units assessed the volume reduction process.

Cell recoveries after processing of the HES and Optipress II methods were as follows: TNC: 74.7±8.2% and 78.7±7.8%, respectively; Lymphocytes: 74.5±9.4% and 80.9±16.3%, respectively. Thus, a significant percentage of progenitor cells were lost with both methods of RBC depletion.

The CB units processed in both groups had comparable volume and cells counts before and after volume reduction, except for number of red blood cells (RBCs), which was significantly greater for the Optipress II group. Recoveries of CD34+ and RBC depletion were significantly better for the HES group. For routine processing, TNC and lymphocyte recoveries were significantly better for CB units processed by the Optipress II system. There was, however, significantly less depletion of RBCs for this group. The time required for CB processing with the Optipress II was significantly shorter than the time needed for volume reduction by addition of HES (25+/-5 min vs. 55+/-10 min).