A THREE-AGE PROJECT
INTRODUCTION
Bone Marrow Transplantation (BMT) is currently the best mode of treatment for certain malignant and non-malignant hematological diseases, imunodeficiency disorders, and genetic abnormalities. This method of treatment consists in the use of high dose of chemotherapy and/or irradiation aiming at eradicating the disease. The intensity of the therapy, however, is so high that destroys the hematopoietic system of the patient. The bone marrow abated needs to be re placed in order to rescue the patient. The bone marrow needs therefore to be transplanted from a related or unrelated donor.
The best donor of bone marrow is an identical twin with the next best possibility being an histocompatibility antigens (HL A) matched sibling. The number of HLA-identical sibling is limited, with a patient having approximately a one-in-four chance of having an identical sibling. Three quarters of the patients who require a bone marrow transplant to be cured of his or her dis ease do not have an identical sibling donor. Since the number of HLA-identical sibling is limited, unrelated donor is the only alternative source of bone marrow for transplantation. Human umbilical cord blood (HUCB) represents a unique source of transplant able hematopoietic progenitor cells. HUCB from ... could alleviate some of the problems associated with BMT and the stablisment of HUCB Banks in registries could become an easily available source of suitable stem cells for transplantation of patients who do not have an identical sibling donor.
Studies suggest that cord blood cells have a great potential as a source of stem cells once they have a unique capacity of rapidly becoming "tolerant" to histocompatibility genetic differences even when transplanted to a patient with major degrees of histoincompatibility, in other words, even in the presence of immunogenetic differences between donor and recipient most of the transplants are successful as HUCB cells are more tolerant to these differences.
Gene therapy represents an extraordinarily promising therapeutic technique for treatment of malignant and non-malignant disease. It has been seen by many researchers as the magic bullet for treatment of cancer in the future. Progenitor cells blood may als o provide an excellent vehicle for a future gene therapy. Therefore, the establishment of large cord blood banks is of the utmost importance in the future.
The alternative for patients who do not have the identical sibling donor is the search for an unrelated identical donor in international banks of bone marrow donors. This source of stem cells for a bone marrow transplant has been used occasionally by pati ents in Brazil and other countries in South America, but has major limitations. The first major limitation is t hat the time between the preliminary search and the final identification of the donor take an average of six months before the transplant is done. This time is too long and the majority of the patients do die of the disease progression before the transpla nt is done. The second major limitation are the costs and the third is the development of graft versus host disease in as many as 6% of the patients transplanted from an unrelated donor; this syndrome is due to the development of reaction of the transplan ted cells which do not recognize normal cells of the recipient as familiar and in such situation attack the normal tissues of the recipient and represent a major problem in the management of bone marrow transplant patients.
By establishing banks of HUCB we could treat more than 60% of patients who potentially can be cured but who lack a fully-matched donor. In addition, the unsatisfactory results obtained using unrelated donors and the difficulty in compiling bone marrow reg istries point to the need for the greater use of the HUCB for transplantation, even in the developed world.
Due to the difficulty of finding compatible donors in unrelated bone marrow banks the establishment of HUCB has grown in the United States and Europe. In Brazil, even if we had the resources to search and use donors from the United States of America and E urope banks, there would be fewer chances of finding a potential donor with the least likelihood of causing either failure on the graft or severe graft versus host disease. The ideal source of stem cells from HUCB must contemplate donors with ethnic similarities, as immunogenetic differences are less likely to happen when this donor and recipient belong to a population with the least degree of ethnic differences.
In summary, there are two major advantages of banking HUCB over bone marrow in Brazil:
1. Possible immunogenetic advantages with regard to tolerance induction, which may allow transplant across broader HLA disparities.
The HUCB as source of readily available unrelated ste m-cells will significantly shorten the waiting time for an unrelated transplant. A cryopreserved HUCB bank has a readily available pool of cells that can be used immediately once the HLA identification is matched. in the contrary the living individual wil ling to donate his bone marrow requires a long search that takes average of 6 to 8 months before all arrangements and tests are done before transplanting.
2.1. To stablish a HUBC bank at the Hospital de Clínicas in Porto Alegre
2.2. To provide stem-cells for bone marrow transplants and supply bone marrow transplant centers in Brazil, in South America with stem-cells.
3.1. Collecting and processing
The extremely valuable source of transplantable hematopoietic stem-cells in the placenta and umbilical cord is normally discarded after the delivery procedure. Cord blood will be harvested without risk to the mother or infant. The task of collection of co rd blood is remarkably simple but requires patience, attention to detailed precision and expertise of the obstetrical team.
The cord blood harvest is aimed at collecting as much blood as possible. For collection a closed system is used by drawing the blood from a venipuncture of the umbilical vein after the delivery of the placenta, while holding the placenta at its edges and suspending it from a frame to avoid collapse of the umbilical veins and their tributaries.
The harvesting should be with the placenta in the uterus after the delivery of the infant taking the advant age of the uterine contractions which allows the recovery of additional 100 ccs of mill.
The collection volume of umbilical cord should be of approximately 100cc. The onset of blood clotting in umbilical cord and placenta veins is slow, a slight delay in retrieving the blood is permissible. Citrate is used as anticoagulant.
3.2. Cryopreservation and separation
Dimethyl sulfoxide (DMSO)is used as cryoprotectant and the cooling rate is optimized for leukocyte viability rather the erythrocytes. The frozen placental blood units are kept in the liquid phase of liquid nitrogen.
4. Materials and equipment needed
5. Potentials of the present project
5.1. The establishment of this project will be supported by partnership among several known governmental institutions. The running costs will be paid for by the Hospital de Clínicas de Porto Alegre, which is the teaching hospital for the Federal University of Rio Grande do Sul, where the tank will be located.
5.2 There will be an active participation in the d evelopment and establishment of the project by members of the community, members indicated by the Rotary and members representing the Hospital de Clínicas de Porto Alegre.