Evaluation of clinical efficacy of single-unit unrelated umbilical cord blood transplantation based on umbilical cord blood provided by China's public cord blood bank / 中华器官移植杂志

Objective To study the curative efficacy and safety of single-unit umbilical cord blood transplantation (sUCBT) for malignant hematologic diseases,which is provided by China's public cord blood bank.Methods We retrospectively analyzed 409 cases of malignant hematologic diseases who accepted myeloablative single-unit unrelated donor UCBT without ATG at our center between May 2008 and December 2016.A comparative analysis was made on the total nuclear cells (TNC) of the umbilical cord blood before freezing and after thawing,the cells of CD34+,the recovery rate of cells and the clinical effect of UCBT.Result 409 units of umbilical cord blood used in UCBT respectively came from eight China's public cord blood banks.The average TNC of 409 units of umbilical cord blood before freezing and after the tubular recovery were respectively 18.5 × 108 and 16.34 × 108 (p =0.000).The average recovery rate of the tubular recovery was 88.5％,and there was significant difference among cord blood banks (P =0.000).The average TNC of umbilical cord blood before freezing and transfusion were respectively 18.5 × 108 and 15.86 × 108 (p =0.000).The average recovery rate of umbilical cord blood transfusion was 85.9％,with the difference being significant among cord blood banks (P =0.000).The average number of CD34+ cells before freezing and after the tubular recovery was 11.18 × 106and 8.68 × 106 (p =0.000).The average recovery rate of CD34+ cells after the tubular recovery was 80.75 ％,with the difference being significant among the cord blood banks (P =0.000).At 42nd day after UCBT,the cumulative incidence of neutrophil engraftment was 95.4％,and the median time of the engraftment was 17 days (11-38 days).The cumulative incidence of platelet engraftment at 120th day was 84.6％,and the median time of the engraftment was 36 days (14-93 days).The cumulative incidence of erythrocyte engraftment at 60th day was 92％,and the median time of engraftment was 22 days (9d-60 days).After the umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of engraftment.The P values for cumulative incidence of neutrophil,platelet and erythrocyte engraftment were respectively 0.004,0.01 and 0.000 2,with the differences being statistically significant.At 100th day after UCBT,the cumulative incidence of Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees of acute graft-versus-host disease (aGVHD) was respectively 28.63％ and 15.7％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of aGVHD.There was no significant difference between Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees (P =0.809 and 0.68 respectively).At 3rd year after UCBT,the cumulative incidence of relapse was 15.89％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the cumulative incidence of relapse (P =0.898).At 3rd year after UCBT,the overall survival (OS) rate and disease free survival (DFS) rate were respectively 66.7％ and 59％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in OS and DFS.There was no significant difference in OS and DFS (P =0.566 and 0.703 respectively).At 3rd year after sUCBT,the rate of graft-versus-host diseases/relapse-free survival (GRFS) was 54.3％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the rate of GRFS (P =0.449).Conclusion The umbilical cord blood provided by China's public cord blood bank was used in UCBT.It has a high safety and good efficacy in treating malignant hematologic diseases.But it needs to set up the standardized and normalized quality-control system of umbilical cord blood for China's public cord blood bank.

Current Status for Cord Blood Transplantation and Public Cord Blood Bank in Korea / 대한수혈학회지

Cord blood is one of the promising sources of hematopoietic stem cell and the public cord blood bank should cryopreserve only high quality, conforming cord blood units for transplantation. Cryopreserved cord blood units have several advantages over other hematopoietic stem cell sources such as bone marrow or mobilized peripheral stem cells; cord blood is in the ready-to-use state after the necessary testing and cause less graft-versus-host disease due to cellular immaturity. The limiting factor is the restricted cell number, which resulted in delayed engraftment and immunologic reconstitution. Selection of cord blood for patients is determined by two criteria: the number of total nucleated cell and the matching of human leukocyte antigen. The cord blood inventory required for any given ethnicity is determined by HLA diversity. In terms of growing interest of cord blood as a stem cell source, we reviewed the current status of cord blood related issues in Korea.

Cord Blood-Current Status and Perspective

Umbilical cord blood (CB) is increasingly used as a source of stem cells to repopulate bone marrow in the treatment of life-threatening diseases in children and adults. I review the relationship between the placenta and circulating CB stem cells for hematopoiesis, the clinical results of cord blood stem cell transplantation, and I particularly emphasizethe criteria of CB donor choice. The scientific progress for the use of CB has resulted in the organization of CB banks all over the world. I also review the status of CB banks and networking systems worldwide as recipients of government-based political support.

Current Status of Cord Blood Banks in Korea / 대한혈액학회지

OBJECTIVES: We analysed the current situation of public and family cord blood banks in Korea to provide the foundation for national cord blood networking system. METHODS: Surveys had sent out to 13-cord blood banks in the nation. Data were collected from 9 out of those 13 banks who replied the survey. Collected data were separated into several categories, and then preceded to comparative analysis. Each categories were as follows; the methods of collection and transportation of cord blood that are currently stored, laboratory profiles prior to storage, the system of storage, and the number of total nucleated cell (TNC) counts and CD34+ cell counts. The numerical distribution of cord blood units per TNC and CD34+ cell counts were analyzed. Also the proportion of transplantation eligible cord blood was analyzed as based on TNC counts and CD34+ cell counts per recipient's weight. RESULTS: This study confirmed the presence of 3-public cord blood banks, 3-public/family cord blood banks and 7-family cord blood banks in the country. Total of 14,497 units of cord blood were stored for public purpose (included 14,397 units of cord blood in 25~50mL volume freezer bag and 100 units of cord blood in vial) at the time of study (Jan, 2003). A number of similarities were noted in the methods of collection, transportation of cord blood and the laboratory profiles prior to storage from each bank. However, there were differences when it comes to the processing and method of storage. The HLA typing were examined by DNA analysis of either PCR-SSOP (sequence specific oligonucleotide probe) or PCR-SSP (sequence specific primer). TNC counts were found from 14,204 units (98%) of stored cord blood but the CD34+ cell counts were detected only from 3,283 units (22.6%) out of total of 14,497 units. The median number of TNC counts and CD34+ cell counts from the stored cord blood were 7.9+/-3.6x108 (1.24~71.8x108) and 2.0+/-1.9x106 (0.04~39.2x106). CONCLUSION: At present, our country keeps as much public cord bloods as foreign banks do. However, the public cord blood banks for actual patients were not facilitated well enough due to poor quality control for cord blood banks and exaggerated advertisement of family cord blood banking. This research suggests the establishment of public medical service that is led by government for the sake of public health.

Standardization of Cord Blood Separation Method for Establishment of Korean Cord Blood Bank / 대한혈액학회지

BACKGROUND: To standardize the separation method of cord blood and establish the Korean Cord Blood Bank, we analysed the data regarding cord blood separation from 8 different hospitals which involved in cord blood banking project. METHODS: We analysed 306 samples which collected with heparinized syringes and separated within 24 hours by Ficoll-Hypaque density gradient separation method and RBC depletion method with 3% gelatin. We performed the mononuclear cell (MNC) count, viability, CD34+ cell count and CFU-GM count following separation of cord blood. We assessed the yield of hematopoietic stem cells by different separation methods in 9 hospitals and the variability among hospitals which performed cord blood separation by same method. RESULTS: 1) In 204 samples of cord blood separated with Ficoll-Hypaque, there were significant differences in MNC count, viability, CD34+ cell count and CFU-GM count among all engaged hospitals, but not in each individual hospital. 2) In 102 samples of cord blood separated with 3% gelatin, there were significant differences in viability, CFU-GM count and CD34+ cell count among all engaged hospitals, but not in MNC count. 3) The yield of MNCs, CD34+ cells and CFU-GM was higher in the cord blood separated with 3% gelatin than Ficoll-Hypaque. CONCLUSION: We suggest that RBC depletion method with 3% gelatin would be better than Ficoll-Hypaque method in order to increase the yield of hematopoietic stem cells and standardize the method of cord blood separation.

Establishment of Cord Blood Stem Cell Bank in Korea / 대한소아혈액종양학회지

PURPOSE: The needs of stem cell transplantation are increasing in Korea under the circumstance of medical insurance coverage since 1996. But allogeneic bone marrow transplants have the limitation in acquisition of matched donor because of small number of siblings in modern society. Although unrelated stem cell transplantations were made possible in Korea with the establishment of Korean Marrow Donor Program, less than one third of patients who need stem cell transplantation are seeking the matched donors through this program and it still takes too much time and efforts. In this clinical setting, cord blood offers an exciting alternative to traditional sources of stem cells. To implement the widespread clinical use of cord blood stem cells, it is necessary to establish the cord blood bank from which stem cell specimens are obtained. METHODS: To establish the cord blood bank in Korea, we started to develop the proper methods to obtain the cord bloods. Various ways of collecting the cord bloods, separation of red blood cells and storage methods were tried and the standard recommendations were made. RESULTS: Mean volume of collected umbilical cord blood was above 70mL by open or closed method in vaginal delivery and cesarean section. Among the RBC depletion methods by using 3% gelatin, Ficoll-Hypaque, or modified Ficoll-Hypaque method, 3% gelatin sedimentation showed the best result in viability and number of mononuclear cells(MNC), CD34+ cell, and day 14 CFU-GM. The recovery rate after freezing-thawing MNC was higher in the group of using 10% DMSO and programmed freezer starting from 4degrees C than in the group of using mixed with DMSO and hydroxyethyl starch and without programmed freezer. Nine patients underwent cord blood transplantation until December 1998. Among them, 6 patients showed the long-term successful engraftment. CONCLUSION: We have developed simple, efficient, and reproducible methods for collection, processing, and storage of cord blood to establish the cord blood bank. There are some administrative issues including the legal and financial problems that possibly will be resolved by the support of the government and the medical team.

The Amount of Hematopoietic Stem Cell and the Distribution of HLA in Human Cord Blood: Basic Study for the Development of Cord Blood Bank / 대한혈액학회지

BACKGROUND: Because there are lower incidence of graft versus host disease in HLA mismatched cord blood transplantation compared to bone marrow transplantation, development of smaller scale cord blood bank could be possible. So we analysed the content of hematopoietic stem cell in cord blood and the distribution of HLA as a basic study for cord blood bank. METHODS: Seventy eight cord bloods were collected in heparinized bottle immediately after caesarian section. After expulsion of placenta, additional cord blood and placental blood were collected with heparinized syringe. Fifteen mL was sent to the laboratory for analysis and the rest was cryopreserved. RESULTS: The mean collected cord blood volume was 96.8mL (range, 55~163mL). And mean 81.8mL (range, 40~148mL) was cryopreserved. It contained mean 7.4x108 (range, 2.8x108~12.2x108) nucleated cells. In 2x105 mononuclear cells, 85 +/- 48 BFU-E, 19 +/- 17 CFU-E, 107 +/- 73 CFU-GM and 124 +/- 113 CFU-GEMM were present. With dextran/albumin thawing media, the viability of cryopreserved cord blood mononuclear cell was better than usual washing method with IMDM (82.3% vs. 74.6% P=0.004). Each cord blood could findHLA full matched, 5 loci matched and 4 loci matched cord blood in the remainders with the probability of 0, 11.9% and 58.4%. CONCLUSION: Development of more smaller scale cord blood bank could be possible compared to bone marrow bank.