BONE MARROW DONORS REGISTRY RESEARCH GROUP
Department of Haematology & Immunology
Faculty of Medical Sciences, College of Medicine
University of Nigeria Enugu Campus (UNEC), Enugu
Department of Haematology & Immunology
Faculty of Medical Sciences, College of Medicine
University of Nigeria Enugu Campus (UNEC), Enugu
Name of Research Group: BONE MARROW DONORS REGISTRY RESEARCH GROUP
Background:
Currently, Haematopoietic Stem Cell Transplantation (HSCT) is the only known curative form of therapy for various malignant and non-malignant haematological disorders. However, a critical limiting factor is the availability of matched human leukocyte antigen (HLA) donors.
Background:
Currently, Haematopoietic Stem Cell Transplantation (HSCT) is the only known curative form of therapy for various malignant and non-malignant haematological disorders. However, a critical limiting factor is the availability of matched human leukocyte antigen (HLA) donors.
Western bone marrow registries have extreme paucity of matching volunteer donors of Nigerian/African origin. Whereas 70% of whites easily find perfect matches, less than 17% of blacks ever succeed. People of African descent are more genetically diverse than Caucasians, making it much more difficult for them to find perfect bone marrow matches. Nigeria’s large and genetically diverse population – over 170 million people and almost 400 distinct ethnic groups – makes it more difficult to get potential donors for Nigerian patients but this also makes it ideal for donor recruitment drives.
Umbilical cord blood holds great promise for paediatric patients, as well as adult patients who cannot find a matching bone marrow donor. However, at the moment, there is no cord blood bank in Nigeria and Africa.
The Bone Marrow Donors Registry in Nigeria (BMRN) has been set up to mobilize volunteer adult stem cell donors whose HLA results will be added to the Registry database from where potential donors can be searched, for use in transplanting patients (both within and outside Nigeria) with benign and malignant haematological and non-haematological disorders.
Our mission is to improve access to genetically diverse stem cell donors from Nigeria and to match patients all over the world with life-saving stem cell donors. We also seek to construct the first cord blood bank in Africa in order to support haematopoietic stem cell research and transplantation.
Donor requirements and Related Donors:
Effective and successful HSCT requires suitable patient selection and treatment protocols, but also a suitable, healthy and available source of haematopoietic stem cells. An HLA-identical sibling or related donor is available for only a fraction of patients due to typical family size and inheritance of two matching parental HLA haplotypes (which will be identical with a chance of only 1 of 4 siblings).
The Bone Marrow Donors Registry in Nigeria (BMRN) has been set up to mobilize volunteer adult stem cell donors whose HLA results will be added to the Registry database from where potential donors can be searched, for use in transplanting patients (both within and outside Nigeria) with benign and malignant haematological and non-haematological disorders.
Our mission is to improve access to genetically diverse stem cell donors from Nigeria and to match patients all over the world with life-saving stem cell donors. We also seek to construct the first cord blood bank in Africa in order to support haematopoietic stem cell research and transplantation.
Donor requirements and Related Donors:
Effective and successful HSCT requires suitable patient selection and treatment protocols, but also a suitable, healthy and available source of haematopoietic stem cells. An HLA-identical sibling or related donor is available for only a fraction of patients due to typical family size and inheritance of two matching parental HLA haplotypes (which will be identical with a chance of only 1 of 4 siblings).
Unrelated Donors:
As an alternative, a well matched volunteer unrelated donor (URD) can be used as a source of stem cells. However, the extreme polymorphism of the HLA alleles within the relevant Major Histocompatibility Complex (MHC) loci limit the success in identifying an allele-matched donor with identity at HLA-A, B, C, DRB1 and possibly DQ1. After 20+ years of experience and well over 50,000 transplants through the National Marrow Donor Program (NMDP), well matched URD HSCT can yield survival nearly as good as transplants using an HLA- identical sibling donor2-4. Favorable survival after URD HSCT requires either matching at all 8 alleles (at HLA-A, B, C and DRB1) or only a single allelic HLA disparity5,6. Using the current standard for an acceptable donor (matching at 7-8 of 8 alleles) yields suitable post-HSCT survival and manageable post-HSCT immunologic complications such as graft-versus-host disease7-9. Patients of western or northern European heritage have a 70-80% chance of identifying a suitable well matched donor while other racial and ethnic populations [Hispanic (45-50%), African-American (25-35%) and Asian (variable by country of origin, but 40-50%)] have less success searching worldwide registries for an available, matching donor10. Thus, populating the Bone Marrow Registry in Nigeria, and ultimately, the Bone Marrow Donors Worldwide (BMDW) with the HLA results of volunteer unrelated diverse genetic Nigerian and African donors, will improve the chances of Nigerian (and African) patients in need of life-saving transplants the chances of getting suitable matched donors.
Umbilical Cord Blood as an alternative graft source:
Umbilical Cord Blood (UCB) available from the post-delivery placenta can provide a rich source of newborn haematopoietic stem cells with favourable ratios of primitive to maturing cells and a naïve population of immunologically functional cells less likely to initiate the toxic complication of GVHD11,12. This immunologically naïve, yet highly proliferative haematologic capacity has allowed the limited cells available in UCB to successfully support haematologic engraftment and immunologic recovery of the patient after HSCT, even if only partial HLA matching between donor and recipient is present. While better matching is preferred, most UCB HSCT have been performed with only 4 of 6 HLA locus matching at HLA-A, B and DRB1, usually tested and matched at intermediate, rather than allele level resolution. With only 550,000 UCB units frozen and available for searching worldwide, developing cord blood banks with high quality and suitably sized units could substantially improve the likelihood of a suitable donor graft, particularly for minority or diverse ethnic populations whose HLA types are not well identified within the world’s adult donor registries12-14. The lesser stringency of HLA matching can allow UCB banking to identify donors for patients without available matched related or unrelated adult volunteer donors.
Donor needs for Nigeria:
There is still an unmet need for patients lacking suitable matched siblings who could benefit from allografting. Expanding volunteer URD registries or UCB banks able to serve a larger population of Nigerian patients requires better understanding of the HLA haplotypes represented in the diverse Nigerian populations. There are over 400 distinct ethnic groups in Nigeria. It is important to identify the various genetic HLA haplotypes to assist in searching for suitable matched donors for patients. Estimating haplotype frequencies within this diverse Nigerian population is critical to effective and thoughtful planning for development of both donor registries and UCB banks.
Significance of the Bone Marrow Donors Registry Research Group
This Reseach Group will provide a detailed estimate of haplotype frequencies across Nigeria as well as the preliminary model for the prospective URD registry and UCB banks for the Nigerian population. These data can inform prospective planning and determine recruitment goals and strategies for both donor registries and UCB banks to better serve Nigerian patients who are potential candidates for HSCT.
Specific Aims:
1. Bone Marrows Donors Recruitment
We plan to recruit unrelated donors from every ethnic group/tribe/race in Nigeria. Their HLA typing results will be added to the database of the Bone Marrow Donors Registry in Nigeria (BMRN) and the Bone Marrow Donors Worldwide (BMDW)
2. We plan to set up Umbilical Cord Blood Banks to make umbilical cord blood stem cells available to patients who are unable to get life saving related donor stem cells and unrelated adult stem cells
3. Haplotype frequency analysis
We propose analysis of HLA typing data within Nigeria in order to define and estimate the frequencies of HLA haplotypes in the Nigerian population. Using the bioinformatics and analytic capabilities available at the National Marrow Donor Program (NMDP) along with linkage data from the millions of donor typings already on file, we propose to analyze HLA typing data obtained from Nigeria recruited donors, patients and their families to define the extent and diversity of HLA haplotypes in the Nigerian population and compare them to haplotype frequencies in other defined international ethnic populations.
Data needs: HLA typing at the highest and most complete resolution available using internationally standard nomenclature and specification of typing techniques.
As an alternative, a well matched volunteer unrelated donor (URD) can be used as a source of stem cells. However, the extreme polymorphism of the HLA alleles within the relevant Major Histocompatibility Complex (MHC) loci limit the success in identifying an allele-matched donor with identity at HLA-A, B, C, DRB1 and possibly DQ1. After 20+ years of experience and well over 50,000 transplants through the National Marrow Donor Program (NMDP), well matched URD HSCT can yield survival nearly as good as transplants using an HLA- identical sibling donor2-4. Favorable survival after URD HSCT requires either matching at all 8 alleles (at HLA-A, B, C and DRB1) or only a single allelic HLA disparity5,6. Using the current standard for an acceptable donor (matching at 7-8 of 8 alleles) yields suitable post-HSCT survival and manageable post-HSCT immunologic complications such as graft-versus-host disease7-9. Patients of western or northern European heritage have a 70-80% chance of identifying a suitable well matched donor while other racial and ethnic populations [Hispanic (45-50%), African-American (25-35%) and Asian (variable by country of origin, but 40-50%)] have less success searching worldwide registries for an available, matching donor10. Thus, populating the Bone Marrow Registry in Nigeria, and ultimately, the Bone Marrow Donors Worldwide (BMDW) with the HLA results of volunteer unrelated diverse genetic Nigerian and African donors, will improve the chances of Nigerian (and African) patients in need of life-saving transplants the chances of getting suitable matched donors.
Umbilical Cord Blood as an alternative graft source:
Umbilical Cord Blood (UCB) available from the post-delivery placenta can provide a rich source of newborn haematopoietic stem cells with favourable ratios of primitive to maturing cells and a naïve population of immunologically functional cells less likely to initiate the toxic complication of GVHD11,12. This immunologically naïve, yet highly proliferative haematologic capacity has allowed the limited cells available in UCB to successfully support haematologic engraftment and immunologic recovery of the patient after HSCT, even if only partial HLA matching between donor and recipient is present. While better matching is preferred, most UCB HSCT have been performed with only 4 of 6 HLA locus matching at HLA-A, B and DRB1, usually tested and matched at intermediate, rather than allele level resolution. With only 550,000 UCB units frozen and available for searching worldwide, developing cord blood banks with high quality and suitably sized units could substantially improve the likelihood of a suitable donor graft, particularly for minority or diverse ethnic populations whose HLA types are not well identified within the world’s adult donor registries12-14. The lesser stringency of HLA matching can allow UCB banking to identify donors for patients without available matched related or unrelated adult volunteer donors.
Donor needs for Nigeria:
There is still an unmet need for patients lacking suitable matched siblings who could benefit from allografting. Expanding volunteer URD registries or UCB banks able to serve a larger population of Nigerian patients requires better understanding of the HLA haplotypes represented in the diverse Nigerian populations. There are over 400 distinct ethnic groups in Nigeria. It is important to identify the various genetic HLA haplotypes to assist in searching for suitable matched donors for patients. Estimating haplotype frequencies within this diverse Nigerian population is critical to effective and thoughtful planning for development of both donor registries and UCB banks.
Significance of the Bone Marrow Donors Registry Research Group
This Reseach Group will provide a detailed estimate of haplotype frequencies across Nigeria as well as the preliminary model for the prospective URD registry and UCB banks for the Nigerian population. These data can inform prospective planning and determine recruitment goals and strategies for both donor registries and UCB banks to better serve Nigerian patients who are potential candidates for HSCT.
Specific Aims:
1. Bone Marrows Donors Recruitment
We plan to recruit unrelated donors from every ethnic group/tribe/race in Nigeria. Their HLA typing results will be added to the database of the Bone Marrow Donors Registry in Nigeria (BMRN) and the Bone Marrow Donors Worldwide (BMDW)
2. We plan to set up Umbilical Cord Blood Banks to make umbilical cord blood stem cells available to patients who are unable to get life saving related donor stem cells and unrelated adult stem cells
3. Haplotype frequency analysis
We propose analysis of HLA typing data within Nigeria in order to define and estimate the frequencies of HLA haplotypes in the Nigerian population. Using the bioinformatics and analytic capabilities available at the National Marrow Donor Program (NMDP) along with linkage data from the millions of donor typings already on file, we propose to analyze HLA typing data obtained from Nigeria recruited donors, patients and their families to define the extent and diversity of HLA haplotypes in the Nigerian population and compare them to haplotype frequencies in other defined international ethnic populations.
Data needs: HLA typing at the highest and most complete resolution available using internationally standard nomenclature and specification of typing techniques.
Future Scientific and Social Benefits of the Research Group:
Guiding Donor Registry and Cord Bank Development
These data which will define HLA haplotype frequencies within Nigerian individuals and subgroups can be immediately beneficial for guiding regional and ethnically-directed donor registry and UCB bank recruitment to supply needed matches for the populations within Nigeria. Planned recruitment can maximize the ethnic and haplotype diversity thereby expanding the utility of donor registries and UCB bank facilities.
Guiding Donor Registry and Cord Bank Development
These data which will define HLA haplotype frequencies within Nigerian individuals and subgroups can be immediately beneficial for guiding regional and ethnically-directed donor registry and UCB bank recruitment to supply needed matches for the populations within Nigeria. Planned recruitment can maximize the ethnic and haplotype diversity thereby expanding the utility of donor registries and UCB bank facilities.
Estimating Donor Search Success
In addition, fundamental data about HLA haplotype frequencies in Nigerian patients searching for HCT donors can be used to inform the likelihood of search success. It can also help to modify current donor search success-estimating algorithms (e.g. NMDP’s HapLogic™) which relies on ethnic haplotype frequency estimates to determine the likelihood of a complete HLA 4 locus (HLA A, B, C, DRB1), 10 allele match for a donor or 6 locus (HLA A, B, DRB1) match for UCB.
When examining a potential donor who is only incompletely HLA typed (i.e. lacking HLA-C or class I allele typing information), these Haplogic estimates can efficiently predict the utility of extended donor searching and further HLA typing. This broad HLA data file for the Nigerian population can substantially improve these search success estimates for the worldwide donor and cord bank searches and thereby improve the accuracy of estimating the availability of potential donors.
Estimating HLA linkage with Disease States
Even more broadly, these data can be used for determining HLA linkage in diseases whose etiology, susceptibility or frequency is related to the MHC. This information will be valuable and will be available for collaborating investigators interested in HLA linkage, disease susceptibility and polymorphism studies in a wide variety of pathologic conditions. Such information can be applied to estimating population susceptibilities and uncovering MHC linkage in disease pathogenesis and to a potentially extensive array of future studies beneficial to scientific discovery and the Nigerian population.
MEMBERS OF THE
‘’BONE MARROW DONORS REGISTRY RESEARCH GROUP’’
UNIVERSITY OF NIGERIA
S/N Name Designation Department
1. Dr. Sunday Ocheni Reader Haematology & immunology
2. Professor Ifeoma Okoye Professor Radiation Medicine
3. Seun Adebiyi, Esq Advocate for Donor Registries American Cancer Society
4. Professor Iheanyi Okpal Professor Haematology & immunology
5. Dr. Obike Ibegbulam Reader Haematology & Immunology
6. Dr. Bartholomew Chukwu Snr Lecturer Paediatrics
7. Dr. Anazoeze Madu Lecturer Haematology & Immunology
9. Dr. Theresa Nwagha Lecturer Haematology & Immunology
In addition, fundamental data about HLA haplotype frequencies in Nigerian patients searching for HCT donors can be used to inform the likelihood of search success. It can also help to modify current donor search success-estimating algorithms (e.g. NMDP’s HapLogic™) which relies on ethnic haplotype frequency estimates to determine the likelihood of a complete HLA 4 locus (HLA A, B, C, DRB1), 10 allele match for a donor or 6 locus (HLA A, B, DRB1) match for UCB.
When examining a potential donor who is only incompletely HLA typed (i.e. lacking HLA-C or class I allele typing information), these Haplogic estimates can efficiently predict the utility of extended donor searching and further HLA typing. This broad HLA data file for the Nigerian population can substantially improve these search success estimates for the worldwide donor and cord bank searches and thereby improve the accuracy of estimating the availability of potential donors.
Estimating HLA linkage with Disease States
Even more broadly, these data can be used for determining HLA linkage in diseases whose etiology, susceptibility or frequency is related to the MHC. This information will be valuable and will be available for collaborating investigators interested in HLA linkage, disease susceptibility and polymorphism studies in a wide variety of pathologic conditions. Such information can be applied to estimating population susceptibilities and uncovering MHC linkage in disease pathogenesis and to a potentially extensive array of future studies beneficial to scientific discovery and the Nigerian population.
MEMBERS OF THE
‘’BONE MARROW DONORS REGISTRY RESEARCH GROUP’’
UNIVERSITY OF NIGERIA
S/N Name Designation Department
1. Dr. Sunday Ocheni Reader Haematology & immunology
2. Professor Ifeoma Okoye Professor Radiation Medicine
3. Seun Adebiyi, Esq Advocate for Donor Registries American Cancer Society
4. Professor Iheanyi Okpal Professor Haematology & immunology
5. Dr. Obike Ibegbulam Reader Haematology & Immunology
6. Dr. Bartholomew Chukwu Snr Lecturer Paediatrics
7. Dr. Anazoeze Madu Lecturer Haematology & Immunology
9. Dr. Theresa Nwagha Lecturer Haematology & Immunology
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