T R A N S P L A N TAT I O N A N D C E L L U L A R E N G I N E E R I N G Improving cord blood unit quantity and quality at King Abdullah International Medical Research Center Cord Blood Bank Dunia Jawdat,1,2 Suha Arab,1 Hadeel Thahery,1 Walid Almashaqbeh,1,4 Ahmed Alaskar,1,2,3 and Ali H. Hajeer2,4

BACKGROUND: Public cord blood banks (CBBs) store cord blood unit (CBU) donations for anyone in need. However, strict regulations need to be followed to build up high-quality bank products that can be used worldwide. We established a public CBB at a tertiary hospital in Saudi Arabia. Here, we investigated the reasons behind rejecting or not collecting CBUs over 2 years (2011-2012) and which steps were implemented to improve the number and quality of storable units. STUDY DESIGN AND METHODS: A total of 2891 mothers were evaluated. Reasons for rejecting donors, not collecting, and rejecting units before or after collection were analyzed and compared for the years 2011 and 2012. RESULTS: A total of 1157 (40%) CBUs were not collected, mainly due to staff availability, and 564 (20%) CBUs were rejected. The main reason for rejecting donations was the mother’s or neonate’s health. Rejecting CBUs after collection was due to low volume. A total of 1170 (40%) CBUs were successfully collected for potential banking and sent for processing; however, 58% were rejected in the laboratory due to low total nucleated cell counts. Several changes were implemented during the 2 years including physician education and awareness, in utero collection, cesarean collection, and staff recruitment. These changes positively affected the numbers of our collected units. Out of the initially eligible mothers in 2011, only 17% were banked; this was increased to 33% in 2012. CONCLUSIONS: We identified the problems with collecting CBUs for banking and will keep improving our selection process of recruiting more CBUs of high quality.

I

n the past several years cord blood (CB) has proven to be a valuable alternative source of hematopoietic stem cells for transplantation to treat hematologic malignancies, metabolic diseases, and immune deficiencies.1-3 Although there are millions of registered marrow donors available, one-third of patients cannot find a suitable donor.4 The advantage of using CB includes prompt availability especially for ethnic minorities, low risk of graft-versus-host disease,5,6 noninvasive procedure with minimum risk factors for the donor, and low risk of transmissible infection.7 The main limitation of using CB is the small amount of blood remaining in the cord or placenta and thus affecting the absolute number of total nucleated cells (TNCs) and hematopoietic progenitor cells in addition to the delayed time of engraftment. As a consequence of the success of CB transplantation many CB banks (CBBs) have been established worldwide.8 We established a public CBB in Saudi Arabia in

ABBREVIATIONS: CB = cord blood; CBB(s) = cord blood bank(s); CBU(s) = cord blood unit(s); TNC(s) = total nucleated cell(s). From the 1Cord Blood Bank, King Abdullah International Medical Research Center; the 2College of Medicine, King Saud bin Abdulaziz University for Health Sciences; the 3Department of Oncology/Adult Haematology and the 4Department of Pathology & Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia. Address reprint requests to: Dunia Jawdat, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, PO Box 22490, Riyadh 11426, Saudi Arabia; e-mail: [email protected]. This work was supported by the King Abdullah International Medical Research Center. Received for publication December 9, 2013; revision received March 2, 2014, and accepted April 11, 2014. doi: 10.1111/trf.12746 © 2014 AABB TRANSFUSION 2014;54:3127-3130. Volume 54, December 2014 TRANSFUSION

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2010. We are aiming to provide high-quality units for anyone in need. However strict regulations need to be followed to build a high-quality bank. The aim of this study was to investigate the main reasons of CB rejection over the past 2 years at the National Guard Hospital in Riyadh, Saudi Arabia.

MATERIALS AND METHODS

integrity, absence of clumps and clots; volume of more than 60 mL; and TNC count of more than 80 × 1013/L using a hematology analyzer (AcT diff, Beckman Coulter, Fullerton, CA). Before cryopreservation, CB units were tested for transmissible diseases and hemoglobin electrophoresis. Before and after processing CB units were tested for sterility by microbiologic testing, CD45+ and CD34+ cell number and viability, using a flow cytometry (BD BioScience, San Jose, CA).

CB collection Written informed consent was obtained from healthy pregnant women by our coordinators 5 days a week. Our program was approved by our institutional review board. CB was collected ex utero in 2011 and in utero from vaginal or cesarean deliveries in 2012. We have two shifts per day, 7 a.m. to 7 p.m. (morning) and 7 p.m. to 7 a.m. (evening). Our weekdays are Sunday to Thursday. In 2011 we collected CB on weekdays only. In April we then added Saturdays. In 2012 we added Friday evenings and then in mid-2012 we added Friday mornings.

Donor eligibility

Statistical analysis Chi-square and Fisher exact tests were used for statistical analysis. p values of less than 0.05 were considered to be significant.

RESULTS A total of 2891 mothers consented for donation. After routine history check-up, 564 (20%) were excluded or their units were rejected. The main reasons for exclusion were the general health of the mother or the baby. The main reason for rejecting collected units was low volume (52%; Table 1). CB from 1157 (40%) donors were not collected for banking, mainly due to staff availability especially during holidays and weekends, emergency cesarean section, and the quality of the cords (Table 2). Out of the total consenting mothers, 1170 (40%) units were collected and sent to

Mothers were eligible to enter our CB donation program if they met our institution inclusion criteria that include: 1) absence of inherited diseases; 2) negative for transmissible diseases including hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-cell lymphotropic viruses Type I and II, and syphilis; and 3) gestation of more than TABLE 1. Reasons for excluding donors or rejecting CBUs before or 34 weeks, absence of any sign of infecafter delivery 2011 to 2012 at KAIMRC-CBB, Saudi Arabia, of 2890 tion, and absence of congenital abnorpotential donors malities in the newborn. Reasons for rejecting 2011 2012 Total

CB testing CB units were maintained at 22 to 24°C until processed using the Sepax method (Biosafe SA, Eysins, Switzerland), within 24 hours and maximum within 48 hours. CB units were processed if they passed the physical check of the bag

Total Before collection Neonatal health Mother health After collection Clotted CB Low volume Others

313/1499

(21)

251/1392

(18)

564/2891

(20)

53 83

(16.9) (26.5)

49 53

(19.5) (21.1)

102 136

(18.1) (24.1)

11 162 4

(3.5) (51.8) (1.3)

12 131 6

(4.8) (52.2) (2.4)

23 293 10

(4.1) (52.0) (1.8)

* Data are reported as number (%). KAIMRC = King Abdullah International Medical Research Center.

TABLE 2. Reasons for not collecting CBUs 2011 to 2012 at KAIMRC-CBB, Saudi Arabia, of 2890 potential donors* Reasons for not collecting Total Neonatal health Cord quality Obstetric reasons Staff availability Others

2011 674/1499 6 122 71 415 60

2012 (45) (0.9) (18.1)† (10.5)† (61.6) (8.9)†

* Data are reported as number (%). † p < 0.05. KAIMRC = King Abdullah International Medical Research Center.

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483/1392 10 40 5 352 76

Total (35) (2.1) (8.3)† (1.0)† (72.9) (15.7)†

1157/2891 16 162 76 767 136

(40) (1.4) (14.0) (6.6) (66.3) (11.8)

IMPROVING CBUs AT KAIMRC-CBB

TABLE 3. Reasons for rejecting units at the laboratory before or after cryopreservation 2011 to 2012 at KAIMRC-CBB, Saudi Arabia, of 1170 potential units* Reason for rejecting Total Before cryopreservation Low TNC count Low volume Clots/clumps >48 hr Others After cryopreservation Bacterial or fungal contamination

2011 253/512 119 10 62 41 18 3.0

(49.0) (47.0)† (4.0)† (24.5)† (16.2)† (7.1) (1.2)

Rejected units 2012 199/658 (30.0) 144 0 29 2 7

(72.4)† (0.0)† (14.6)† (1.0)† (3.5)

17.0

(8.5)

Total 452/1170 263 10 91 43 25 20.0

(39.0) (58.2) (2.2) (20.1) (9.5) (5.5) (4.4)

* Data are reported as number (%). † p < 0.05. KAIMRC = King Abdullah International Medical Research Center.

the laboratory for processing. At the laboratory 435 (37%) were discarded and 735 (63%) were accepted and stored for future use. The main reason for discarding units was low TNC (Table 3). Several steps have been taken to improve our banking; these steps include in utero collection, cesarean collection, increasing the number of shifts covered by our staff, and most importantly educational sessions for labor and delivery staff, as many of our cord blood units (CBUs) were rejected due to improper clamping, draining, rupture, or clotting of the cord. These changes increased our CBUs significantly in 2012 (Tables 2 and 3).

DISCUSSION Selecting mothers for CB donation is an important issue for the quality of the bank. Having a healthy mother does not guarantee a successful collection. Many factors can affect the unit collected.9 Herein we identify some of the limitations of storing CBUs in our bank and the changes we have implemented to improve our banking; collecting low volumes was one of our limitations, we mainly used ex utero method in 2011, which mostly gave us small volumes and more chances of clots as seen by other groups.10 In 2012 we started in utero collections, which positively improved our collection. The quality of the cord was also a major factor since we are a new program; we faced some resistance from the labor and delivery staff in 2011, which poorly affected our collection; however, regular meetings with the staff in 2012 and educational sessions positively improved their collaboration. In addition, in 2011 we used to miss all the cesarean sections but by mid-2012 we completed the training for collecting from cesarean deliveries to avoid unnecessary loss of donors. Staff availability was a challenge in 2011; however, in 2012 we included more shifts and recruited more staff to cover holidays and weekends. Low TNC count was the most common reason for rejection as seen with other banks.11 Some studies have shown the factors that can affect the

TNC count such as placenta weight, newborn sex, and method of delivery.12,13 Since we are a new CBB we are identifying problems with collecting CBUs for banking and will keep working to improve the process of recruiting more CBUs of high quality.

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marrow transplantation. Transplant Proc 2005;37: 3211-2. 8. Barker JN, Byam CE, Kernan NA, et al. Availability of cord blood extends allogeneic hematopoietic stem cell transplant access to racial and ethnic minorities. Biol Blood Marrow Transplant 2010;16:1541-8. 9. Volpe G, Santodirocco M, Di Mauro L, et al. Four phases of checks for exclusion of umbilical cord blood donors. Blood Transfus 2011;9:286-91. 10. Skoric D, Balint B, Petakov M, et al. Collection strategies and cryopreservation of umbilical cord blood. Transfus Med 2007;17:107-13.

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11. Wang TF, Wen SH, Yang KL, et al. Reasons for exclusion of 6820 umbilical cord blood donations in a public cord blood bank. Transfusion 2014;54:231-7. 12. Yang H, Loutfy MR, Mayerhofer S, et al. Factors affecting banking quality of umbilical cord blood for transplantation. Transfusion 2011;51:284-92. 13. Keersmaekers CL, Mason BA, Keersmaekers J, et al. Factors affecting umbilical cord blood stem cell suitability for transplantation in an in utero collection program. Transfusion 2014;54:545-9.

Improving cord blood unit quantity and quality at King Abdullah International Medical Research Center Cord Blood Bank.

Public cord blood banks (CBBs) store cord blood unit (CBU) donations for anyone in need. However, strict regulations need to be followed to build up h...
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