EDITORIAL Current challenges for public cord blood banks
I
n this edition of TRANSFUSION, Yoon and colleagues1 report on a method to estimate the minimum desired size of cord blood bank activity to meet the public cord blood bank needs of the South Korean population. Necessarily, the estimates are based on current thinking about selection criteria for cord blood units in transplantation, specifically what constitutes an acceptable HLA match of a cord blood unit for the patient. While the method may benefit from additional refinement such as the use of a broader cross-section of the population and high-resolution typing of the current cord blood inventory, the stated goal of estimating a minimum capacity can be achieved by this approach. In addition, the article notes that developing a truly useful inventory estimate must take into consideration the total nucleated cell (TNC) count of the banked units to provide sufficient dose to meet the needs of the targeted population. What might be considered a minimum registry size today will continue to evolve as further studies are published based on cord blood transplant outcomes. For instance, Eapen and colleagues2 recently showed that matching at the HLA C locus should be considered in graft selection, as well as using high-resolution typing generally. These additional considerations reinforce the conclusion reached in the article by Yoon and colleagues that the method used only serves to estimate a minimum size inventory, and if these or other additional match considerations are taken into account, the ideal inventory size may be significantly larger than that projected using current selection criteria. The World Marrow Donor Association (WMDA) estimates that through 2012 there were more than 30,000 cord blood units used in transplantation since the first unrelated cord blood transplant was performed in 1993.3 In 2012, a total of 4150 units were shipped for use in transplantation worldwide. While it is difficult to determine precisely how many transplants these units represented since some were used in multiple-unit cord blood transplants, in the United States, 22% of the unrelated transplants facilitated through the National Marrow Donor Program in 2012 used cord blood units as the primary graft. The value of cord blood transplantation within the range of options available to patients is well established. The outcomes reported by the various groups in Japan suggest that cord blood has a significant and likely enduring place in unrelated transplantation in that relatively © 2014 AABB TRANSFUSION 2014;54:499-500.
homogeneous population. And in the United States, with a very heterogeneous population, patients in need of a transplant who lack a well-matched adult donor also can benefit from a large and well-characterized cord blood inventory. This opportunity has been demonstrated by the fact that cord blood represents the source of cells for more than 35% of the minority population receiving an unrelated donor transplant within the United States. An increasing number of cord blood units available in the United States has meant not only better matches for this population, but also a greater supply of cord blood units with sufficient TNC counts for use in adults as well as children. The WMDA data also show that cord blood in transplantation grew only slightly in 2012, and if the experience in Japan and Korea is removed from the analysis, overall use has decreased. The reason for the relatively static or decreasing application in many countries has been the subject of some speculation within the transplant community. Anecdotal information gathered from both United States and European sources by this author suggests a variety of reasons including 1) the relative cost of the cord blood unit for transplantation versus other sources of cells, especially for adults needing a double cord blood; 2) the higher costs of other health care services associated with a cord blood transplant relative to other sources of cells; 3) the higher incidence of nonengraftment; and 4) the lack of experience managing the cord blood transplant patient. Studies are ongoing that may address some of the shortcomings of cord blood transplantation. These include graft manipulation through T-cell depletion of the second graft, enhancement of the graft with mesenchymal stem cells, expansion of the graft itself, and use of a haploidentical donor to bridge to a cord blood transplant. While many of these approaches are promising, as yet there are neither sufficient data to indicate convincingly that engraftment time can be shortened nor outcomes that are significantly compelling to overcome some of the concerns about cord blood transplantation. More recently, haploidentical transplants have emerged as another alternative where a fully matched adult donor may not be available.4 On a worldwide basis, cord blood banks continue to add to their inventory. In 2012, WMDA reports that an additional 70,036 cord blood units were added to the world’s inventory. While this number suggests impressive growth, modeling done by the Swiss and US registries indicates that the current demand for cord blood cannot Volume 54, March 2014 TRANSFUSION
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EDITORIAL
economically sustain the growth of inventories in many countries without subsidies from governmental or other sources.5 While the demand for cord blood varies from country to country, only a few countries such as Japan have sufficient utilization to continue to increase the cord blood inventory at a meaningful rate to achieve an inventory size based on estimates using the Korean method. Given the significant investment required to recruit and bank a sufficient number of cells to meet even the minimum criteria, the identification of additional factors to improve outcomes through better matching for cord blood transplantation signals that an “ideal” inventory size may be difficult to attain in many countries. However, for the foreseeable future, publicly banked cord blood units represent an important alternative for many patients around the globe who cannot find a suitable adult donor match. Over the past 30 years, many countries have invested significantly in the growth of the adult donor registries to ensure an adequate match for most of their population. A comparable investment in cord blood inventory should be studied to determine whether this investment of resources would increase the likelihood of finding a match for those unable to find a match on the adult donor registries.6 It is unlikely that the demand alone for cord blood transplant will be able to drive the necessary investment that is needed to achieve the minimum inventories that might be required in each country. This status is likely to remain, until use of cord blood is demonstrated to improve outcomes beyond the current results seen in transplantation today.
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TRANSFUSION Volume 54, March 2014
CONFLICT OF INTEREST The author reports no conflicts of interest or funding sources.
Michael Boo, JD National Marrow Donor Program Minneapolis, MN e-mail: [email protected]
REFERENCES 1. Yoon JH, Oh S, Shin S, et al. The minimum number of cord blood units needed for Koreans is 51,000. Transfusion 2014;54:504-8. 2. Eapen M, Klein JP, Sanz GF, et al. Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. Lancet Oncol 2011;12:1214-21. 3. World Marrow Donor Association. Unrelated cord blood banks/registries annual report 2012. 14th ed. Leiden: WMDA; 2013. 4. Alshemmari S, Ameen R, Gaziev J. Haploidentical hematopoietic stem-cell transplantation in adults. Bone Marrow Res 2011;2011: 303487. 5. Bart T, Boo M, Balabanova S, et al. Impact of selection of cord blood units from the United States and Swiss registries on the cost of banking operations. Transfus Med Hemother 2013;40:14-20. 6. Bart T. Cost effectiveness of cord blood versus bone marrow and peripheral blood stem cells. Clinicoecon Outcomes Res 2010;2:141-7.
I
n this edition of TRANSFUSION, Yoon and colleagues1 report on a method to estimate the minimum desired size of cord blood bank activity to meet the public cord blood bank needs of the South Korean population. Necessarily, the estimates are based on current thinking about selection criteria for cord blood units in transplantation, specifically what constitutes an acceptable HLA match of a cord blood unit for the patient. While the method may benefit from additional refinement such as the use of a broader cross-section of the population and high-resolution typing of the current cord blood inventory, the stated goal of estimating a minimum capacity can be achieved by this approach. In addition, the article notes that developing a truly useful inventory estimate must take into consideration the total nucleated cell (TNC) count of the banked units to provide sufficient dose to meet the needs of the targeted population. What might be considered a minimum registry size today will continue to evolve as further studies are published based on cord blood transplant outcomes. For instance, Eapen and colleagues2 recently showed that matching at the HLA C locus should be considered in graft selection, as well as using high-resolution typing generally. These additional considerations reinforce the conclusion reached in the article by Yoon and colleagues that the method used only serves to estimate a minimum size inventory, and if these or other additional match considerations are taken into account, the ideal inventory size may be significantly larger than that projected using current selection criteria. The World Marrow Donor Association (WMDA) estimates that through 2012 there were more than 30,000 cord blood units used in transplantation since the first unrelated cord blood transplant was performed in 1993.3 In 2012, a total of 4150 units were shipped for use in transplantation worldwide. While it is difficult to determine precisely how many transplants these units represented since some were used in multiple-unit cord blood transplants, in the United States, 22% of the unrelated transplants facilitated through the National Marrow Donor Program in 2012 used cord blood units as the primary graft. The value of cord blood transplantation within the range of options available to patients is well established. The outcomes reported by the various groups in Japan suggest that cord blood has a significant and likely enduring place in unrelated transplantation in that relatively © 2014 AABB TRANSFUSION 2014;54:499-500.
homogeneous population. And in the United States, with a very heterogeneous population, patients in need of a transplant who lack a well-matched adult donor also can benefit from a large and well-characterized cord blood inventory. This opportunity has been demonstrated by the fact that cord blood represents the source of cells for more than 35% of the minority population receiving an unrelated donor transplant within the United States. An increasing number of cord blood units available in the United States has meant not only better matches for this population, but also a greater supply of cord blood units with sufficient TNC counts for use in adults as well as children. The WMDA data also show that cord blood in transplantation grew only slightly in 2012, and if the experience in Japan and Korea is removed from the analysis, overall use has decreased. The reason for the relatively static or decreasing application in many countries has been the subject of some speculation within the transplant community. Anecdotal information gathered from both United States and European sources by this author suggests a variety of reasons including 1) the relative cost of the cord blood unit for transplantation versus other sources of cells, especially for adults needing a double cord blood; 2) the higher costs of other health care services associated with a cord blood transplant relative to other sources of cells; 3) the higher incidence of nonengraftment; and 4) the lack of experience managing the cord blood transplant patient. Studies are ongoing that may address some of the shortcomings of cord blood transplantation. These include graft manipulation through T-cell depletion of the second graft, enhancement of the graft with mesenchymal stem cells, expansion of the graft itself, and use of a haploidentical donor to bridge to a cord blood transplant. While many of these approaches are promising, as yet there are neither sufficient data to indicate convincingly that engraftment time can be shortened nor outcomes that are significantly compelling to overcome some of the concerns about cord blood transplantation. More recently, haploidentical transplants have emerged as another alternative where a fully matched adult donor may not be available.4 On a worldwide basis, cord blood banks continue to add to their inventory. In 2012, WMDA reports that an additional 70,036 cord blood units were added to the world’s inventory. While this number suggests impressive growth, modeling done by the Swiss and US registries indicates that the current demand for cord blood cannot Volume 54, March 2014 TRANSFUSION
499
EDITORIAL
economically sustain the growth of inventories in many countries without subsidies from governmental or other sources.5 While the demand for cord blood varies from country to country, only a few countries such as Japan have sufficient utilization to continue to increase the cord blood inventory at a meaningful rate to achieve an inventory size based on estimates using the Korean method. Given the significant investment required to recruit and bank a sufficient number of cells to meet even the minimum criteria, the identification of additional factors to improve outcomes through better matching for cord blood transplantation signals that an “ideal” inventory size may be difficult to attain in many countries. However, for the foreseeable future, publicly banked cord blood units represent an important alternative for many patients around the globe who cannot find a suitable adult donor match. Over the past 30 years, many countries have invested significantly in the growth of the adult donor registries to ensure an adequate match for most of their population. A comparable investment in cord blood inventory should be studied to determine whether this investment of resources would increase the likelihood of finding a match for those unable to find a match on the adult donor registries.6 It is unlikely that the demand alone for cord blood transplant will be able to drive the necessary investment that is needed to achieve the minimum inventories that might be required in each country. This status is likely to remain, until use of cord blood is demonstrated to improve outcomes beyond the current results seen in transplantation today.
500
TRANSFUSION Volume 54, March 2014
CONFLICT OF INTEREST The author reports no conflicts of interest or funding sources.
Michael Boo, JD National Marrow Donor Program Minneapolis, MN e-mail: [email protected]
REFERENCES 1. Yoon JH, Oh S, Shin S, et al. The minimum number of cord blood units needed for Koreans is 51,000. Transfusion 2014;54:504-8. 2. Eapen M, Klein JP, Sanz GF, et al. Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis. Lancet Oncol 2011;12:1214-21. 3. World Marrow Donor Association. Unrelated cord blood banks/registries annual report 2012. 14th ed. Leiden: WMDA; 2013. 4. Alshemmari S, Ameen R, Gaziev J. Haploidentical hematopoietic stem-cell transplantation in adults. Bone Marrow Res 2011;2011: 303487. 5. Bart T, Boo M, Balabanova S, et al. Impact of selection of cord blood units from the United States and Swiss registries on the cost of banking operations. Transfus Med Hemother 2013;40:14-20. 6. Bart T. Cost effectiveness of cord blood versus bone marrow and peripheral blood stem cells. Clinicoecon Outcomes Res 2010;2:141-7.
