cord blood stem cell transplantation study (coblt)

Conditions: Anemia, Aplastic; Fanconi Anemia; Hematologic Diseases; Leukemia; Neoplasms; Severe Combined Immunodeficiency; Hematopoietic Stem Cell Transplantation; Myelodysplastic Syndromes

Summary: to evaluate if hla-mismatched, unrelated-donor umbilical cord blood stem and progenitor cell units (ucbu) offered a clinically acceptable alternative to matched unrelated-donor allogeneic bone marrow for transplantation with 180-day disease free survival as the endpoint. hla typing was performed using dna-base high resolution methods to determine hla alleles. patients with "true" hla 3/6 and 4/6 matches were evaluated. in addition, a separate study in adults addressed the problem of limited cell dose and engraftment failure. the study was not planned as a randomized comparative clinical trial. instead, it is a phase ii/iii efficacy study.

background: bone marrow transplantation is an effective therapy for a variety of genetic and hematologic disorders. donated bone marrow, which provides a source of stem and progenitor cells for bone marrow reconstitution, is obtained either from related donors, usually hla-matched siblings, or from hla-matched unrelated donors. because of the limited availability of hla-matched related donors, hla-matched unrelated donors are frequently the only alternative source of bone marrow for transplantation. to provide matched volunteer bone marrow donors for unrelated recipients, the national marrow donor program (nmdp) was established in 1986 to develop a national registry of hla-typed individuals who agree to donate bone marrow if needed. more than 3 million potential marrow donors are now enrolled. a limitation of the registry approach is the time needed to identify a donor and complete the necessary clinical evaluation and laboratory testing for histocompatibility, infectious diseases, and general good health. moreover, a certain proportion of potential donors change their minds or otherwise become unavailable between the time they enter the registry and the time they are called as a preliminary match for a patient. another disadvantage is the marrow harvesting procedure which requires the normal donor to be hospitalized and given general anesthesia in an operating room. finally, the nmdp registry consists of potential donors that are primarily of european caucasian ancestry. although great strides have been made in increasing the numbers of african-americans, hispanics, asian-americans, and native americans, it is still more difficult to find matches for these ethnic minorities than for caucasian patients. human umbilical cord blood is an alternative source of hematopoietic stem and progenitor cells capable of reconstituting the bone marrow of recipients with a variety of diseases. cord blood stem and progenitor cells from related donors have been successfully transplanted world-wide in children with genetic or hematologic diseases. these results suggested that cord blood from unrelated, hla-matched donors also can be used for patients who need a transplant but don't have a related donor. the existing problems in unrelated-donor bone marrow transplantation with donor recruitment, bone marrow harvesting, and matching for antigens peculiar to a particular ethnic group would be reduced if typed, tested, and frozen umbilical cord blood could be made easily and rapidly available. such a system, which could complement or partially replace the present process, has been shown to be feasible. in an nhlbi-sponsored program, investigators have collected and cryopreserved a bank of about 9,000 human ucbus. in addition, successful searches and matches (including many 4/6 antigen matches) have resulted in more than 900 unrelated-donor, ucbu transplants to date. preliminary data from both these unrelated-donor and other related-donor cord blood transplants suggest that there is less gvhd than if the source of the graft were adult bone marrow. the severity of gvhd also seems less even in highly mismatched recipients. one important question is whether or not 3/6 hla matched transplants in children will have acceptable 180-day disease free survival. it also remains to be determined if the graft-vs-leukemia effect is also less or if unrelated-donor cord blood grafts are as durable as those from matched, related-donors. most transplants conducted thus far have been in children. hence another important question is whether or not there are sufficient numbers of stem cells in cord blood to support transplantation to an unrelated adult. the initiative was proposed by the division of blood diseases and resources staff and approved by the february 1995 national heart, lung, and blood advisory council. the requests for proposals were released in june 1995. contracts were awarded september 30, 1997. design narrative: the study is multicenter, with six cord blood transplant centers (cbtcs), two collecting and storage centers (cord blood banks -- cbbs) and one coordinating center. each cbb used the same protocol for recruiting donors, collecting, processing, testing, storage, retrieval from storage, reprocessing from the frozen state, and shipping. each participating cbtc used the same patient selection criteria, preparative regimen for patients in the same class, initial graft-versus-host disease (gvhd) prophylaxis, indications for the use of cytokines, definitions for events and complications, and methods for evaluating immune reconstitution. the main study evaluated the impact of hla 3/6 and 4/6 matching on outcome. the primary endpoint was 180-day disease free survival after ucbu transplantation. secondary endpoints included engraftment, the frequency and severity of acute and chronic gvhd with stratification by degree of hla match, overall survival, and immunologic reconstitution. data were collected on banked ucbus to define unit quality by nucleated cell count and flow cytometry of surface markers to identify effects on patient outcome. recruitment ended december 31, 2003 with the accrual of 326 subjects. .

Eligibility criteria:
mothers of infant-donors must complete a medical history form, have an uncomplicated delivery, and deliver at ucla or duke. patients are those who need a transplant but don't have a matched marrow donor or can't wait to find one.