|
Correction
to
Kurtzberg et al.,
|
| |||||||||||||||||||||||||||||||||||
Undoubtedly, repositories of cord-blood stem cells will be widely established. As Silberstein and Jefferies note in their editorial (July 18 issue),3 the potential benefits to adults, society, science, and commercial interests are substantial and include the use of allogeneic stem-cell therapy for malignant conditions and infectious diseases, the discovery of new genetic disorders, the issuing of patents for newly discovered genes, and profit from therapeutic uses.4 However, there is a major gap in drug development between children and adults. Children often do not benefit from drugs developed for adults, and there are now proposals to take cells from infants largely for the benefit of adults.
Infants must be the first to benefit in some way from the use of their own stem cells. Repositories must be called by their scientifically correct name, "infant-stem-cell repositories," not placental repositories. A permanent record of diseases that are diagnosed in the infants should be maintained. Parents should be informed of the diagnoses. Therapy should be offered for treatable diseases. The commercialization of stem cells from infants for therapy should include financial benefit for the infants. Royalties from each stem-cell donation should be placed in a national trust fund to be used for research and the treatment of children with serious and life-threatening diseases. The rights of infants as donors cannot be ignored.
Arthur J. Ammann, M.D.
University of California, San Francisco
San Francisco, CA 94143
References
Francesco Bertolini, M.D., Ph.D.
Gioacchino Robustelli della Cuna, M.D.
I.R.C.C.S. Maugeri Foundation
27100 Pavia, Italy
References
In our four recipients of cord blood we observed an impressive increase in the percentage (up to 50 percent of the lymphocyte population) and absolute number (up to 5000 per cubic millimeter) of CD19+ B cells, which was apparently not related to defective control of Epstein–Barr virus infection, from about two to nine months after cord-blood transplantation. Most of these lymphocytes also expressed CD20 and surface IgM. Moreover, serum levels of IgM and IgA were those expected in children less than one year of age. Recipients of cord blood might repeat the neonate's program of B-cell ontogeny, with antigenic challenge favoring an expansion in the population of B lymphocytes.1 In this regard, it is known that memory B cells reside in adult bone marrow, but that cord blood contains only naive B lymphocytes.
Franco Locatelli, M.D.
Rita Maccario, Ph.D.
Marco Zecca, M.D.
I.R.C.C.S. Policlinico San Matteo
27100 Pavia, Italy
References
Recently, one of our patients, a five-year-old white boy with acute lymphoblastic leukemia in second complete remission, died of grade IV GVHD after receiving placental blood from an Asian donor, provided by the Dusseldorf Placental Blood Bank in Germany. Patient and donor were identical for the class I HLA-A, B, and C loci and class II HLA-DR, with a minor mismatch at the HLA-DQB1 locus (HLA-DQB1*0602 in the case of the patient and HLA-DQB1*0603 in the case of placental blood). Cyclosporine alone was used for GVHD prophylaxis. Although Kurtzberg et al. specify the racial and ethnic origins of their patients, they do not do so for the donors. It would be interesting to know whether Patients 13 and 16, who were mismatched for one and two antigens, respectively, were given placental blood from racially or ethnically different donors. If that was the case, race or ethnic group may have to be taken into account when placental-blood transplantation is being considered.
Manuel M. Abecasis, M.D.
António Guimaraes, M.D.
Alexandra Machado, M.D.
Instituto Portugues de Oncologia
1930 Lisbon, Portugal
To the Editor: We agree that manipulation of the infant during delivery could affect the amount of placental blood collected for banking and transplantation. However, we stress that the placental-blood units banked at the New York Blood Center are collected from the delivered placenta, ex vivo, by a dedicated team whose members have no role in the care of the infant or mother. All units are screened for blood-borne pathogens, including hepatitis B and C virus, human T-cell lymphotropic virus types I and II, HIV, and cytomegalovirus, as well as for hemoglobinopathies. Test results are forwarded to the mother's and infant's physicians.
We agree that children should benefit from this research, and indeed, they do. The majority of transplantations have been performed in children: 44 percent of the 272 patients who have received placental-blood units from the New York Blood Center have been under 6 years of age, and another 29 percent were between the ages of 6 and 11 years. We believe that the blood of the infant donor, which previously was discarded, should be a public resource and that its use should involve no financial gain to any party.
Drs. Bertolini and Robustelli della Cuna question the CD34 cell counts we reported. The numbers are correct, but they represent the total CD34 population, not an immature (e.g., CD34+CD38-) subgroup. We have not observed a correlation between the number of CD34 cells infused and the recovery of the white-cell, platelet, or red-cell count.
To respond to Locatelli et al., we reviewed our information regarding reconstitution of B cells in our patients. Our results agree, in part, with their observation; approximately 50 to 75 percent of our patients had elevated percentages of CD19+ and CD20+ cells 6 to 12 months after transplantation, but no increases in the absolute numbers of B lymphocytes in 27 patients tested at 3 to 6 months and 10 patients tested at >12 months. Since all our patients were given prophylactic intravenous immune globulin during the first year after transplantation, we cannot comment on immunoglobulin production.
To Abecasis et al. we reply that Patient 13 was of Native American and black heritage, and her donor was of white and black heritage. Both Patient 16 and the donor were white.
Finally, we would like to point out that the key to Figure 1 is reversed: 22 patients received placental blood thawed with the new method, and 3 patients received placental blood thawed with the old method.
Joanne Kurtzberg, M.D.
Duke University Medical Center
Durham, NC 27710
Pablo Rubenstein, M.D.
Cladd E. Stevens, M.D.
New York Blood Center
New York, NY 10021
We agree that institutions that propose to collect and store placental blood need to address important medical and ethical issues. It is important to establish guidelines and regulations to ensure medical safety and protect the rights of placental-blood donors and potential recipients. Adherence to such regulations has been standard in the process of volunteer blood donation in this country for decades. We endorse the suggestion that the Food and Drug Administration or another appropriate organization should be responsible for establishing and enforcing similar standards for placental-blood collection.
In all but a very few cases thus far, children rather than adults have received placental blood. It has not been shown that placental blood consistently engrafts in adult-sized recipients, but recipients of placental blood should be selected on the basis of medical need and HLA compatibility. Placental-blood banking will thus benefit adults and children alike. We do not condone the development of commercial banks for allogeneic or autologous banking. On the contrary, we support the concept that in cases in which placental blood would otherwise be discarded (e.g., the great majority of deliveries), this blood represents a commonly owned good that, if collected for potential future transplantation, should be maintained and distributed by publicly accessible banks.
Other ethical issues regarding placental-blood banking include some of those raised by Dr. Ammann. These relate to informed consent for the collection and storage of placental blood, the obligation to notify parents and children of the results of tests performed on placental blood, the assurance of the confidentiality of such information, and the need for equitable access to placental blood.1 Published policies and procedures proposed for placental-blood banks address these issues and would require, for example, that the donor be notified of test results.2
The timing of umbilical-cord clamping at delivery and the position of the infant relative to the placenta affect the volume of blood transfused to the infant and the volume remaining in the umbilical cord and placenta. The availability of placental blood for autotransfusion is of concern primarily in premature infants, who might require emergency resuscitation at delivery or who may benefit from later administration of additional blood.3,4 Proposed policies for placental-blood banks restrict collection to full-term, uncomplicated pregnancies.2 Moreover, in our institution and others, it is stipulated that placental-blood collection cannot interfere with the usual obstetrical practice at delivery and that cord clamping proceed accordingly.
Leigh C. Jefferies, M.D.
Leslie E. Silberstein, M.D.
University of Pennsylvania School of Medicine
Philadelphia, PA 19104
References
| |||||||||||||||||||||||||||||||||||
This article has been cited by other articles:
HOME | SUBSCRIBE | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | PRIVACY | HELP | beta.nejm.org Comments and questions? Please contact us. The New England Journal of Medicine is owned, published, and copyrighted © 2009 Massachusetts Medical Society. All rights reserved. |
Previous
