|Year : 2018 | Volume
| Issue : 1 | Page : 56-58
Urgent need for a South Asian hematopoietic stem cell donor registry
Co-Founder & Chairman, Jeevan Stem Cell Foundation, NGS HLA Laboratory, Public Cord Blood Bank, Bone Marrow Donor Registry; Member, National Apex Committee for Stem Cell Research and Therapy, Ministry of Health, Government of India, Member, Drafting Committee for Regulating Cord Blood and Other Stem Cell Banking, Ministry of Health, Government of India, India
|Date of Web Publication||5-Apr-2018|
Dr. Srinivasan Periathiruvadi
Co-Founder & Chairman, Jeevan Stem Cell Foundation, NGS HLA Laboratory, Public Cord Blood Bank, Bone Marrow Donor Registry; Member, National Apex Committee for Stem Cell Research and Therapy, Ministry of Health, Government of India, Member, Drafting Committee for Regulating Cord Blood and Other Stem Cell Banking, Ministry of Health, Government of India
Source of Support: None, Conflict of Interest: None
For over four decades, Haematopoietic Stem Cell Transplantation remains the only form of curative treatment of patients with blood cancers, Thalassemia and certain congenital immune deficiencies. Poor representation of Asian population in the global donor database and absence of a regional registry for South Asian population is responsible for loss of lives. Hence there is an urgent need for member countries in the SAARC region to work together to enable quick and affordable access to matching stem cells for patients in this region.
Keywords: Blood Cancer, bone marrow donor registry, hematopoietic stem cell transplantation
|How to cite this article:|
Periathiruvadi S. Urgent need for a South Asian hematopoietic stem cell donor registry. Glob J Transfus Med 2018;3:56-8
| Introduction|| |
Approximately 120,000 Indians are diagnosed with blood cancers and other forms of bone marrow disorders potentially curable with allogenic hematopoietic stem cell transplantation. Sri Lanka, Pakistan, and Bangladesh account for another 36,000 cases a year. India alone has a huge burden with an estimated 100,000 patients with β-thalassemia syndrome, and allogeneic stem cell transplantation is unaffordable for the majority of families.
In Bangladesh, 7% of population has some form of inherited hemoglobin abnormality. Globally an estimated 320,000 babies are born each year with a clinically significant hemoglobin disorder, and nearly 80% of these births occur in developing countries.
There are several thousand children in these countries with severe congenital immunodeficiencies and hereditary metabolic disorders.
Since 1959, allogeneic hematopoietic stem cell (HSC) transplantation (intravenous infusion of stem cells) continues to remain as the only potentially curative treatment option for these patients.
The first source of HSC donor is to find a matching sibling. The second option is to find a matched unrelated donor. This can be either an adult donor or a cord blood unit (CBU). Globally, subject to availability of a matching unit, the transplant physician's first preference is an adult donor because of early engraftment and the availability of large number of cells for transplant. With the increasing interest in haplo-transplant, in the past few years, the usage of CBUs has declined because of the limited number of cells available per unit (approximately one billion), delayed engraftment (compared to the adult peripheral blood stem cell [PBSC]), and the challenges associated with delayed engraftment. However, it is hoped that use of expanded cells (www.gamida-cell.com) and modalities such as hyperbaric oxygen  helps shortening the engraftment time. This will result in increased usage of HSCs from the CBUs for those who cannot find a fully matched adult donor, as the human leukocyte antigen (HLA) match for transplant of CBU need not be so stringent.
Haplo-identical donor is an alternative for such patients who cannot find a sibling or matched unrelated donor.
| Challenges Facing South Asian Patients|| |
Ethnic diversity and human leukocyte antigen distribution
HLAs are ethnicity dependent. With the poor representation of the potential donors of Asian origin in the database of over 32 million donors listed by the World Marrow Donor Association (WMDA), the chances of an Asian to find a 10 out of 10 match for HSC transplantation are very low. Consequently, a hope for potential cure through transplantation is far lower for Asian patients compared to Caucasian patients. The size and genetic composition of the registry determine the proportion of patients who will be able to find a suitable match.
Even if one is fortunate to find a HLA match donor, the cost of importing such a unit for transplant would be over USD 30,000 that may be beyond the reach of most of the patients coming from this region.
Our own data confirm the variations of HLA distribution among the major linguistic populations in India, making them multiethnic groups. Added to this challenge, over the past few decades, with increasing number of marriages between these populations, the HLA distribution of future generations is likely to become more heterogeneous. Furthermore, with most families having one child, the hope of sibling as the donor does not exist. India does not have a large enough registry of adult donors or repository of cord blood-derived stem cells. The situation is similar in nature among all the South Asian countries.
Absence of large registries
Learning from global experiences, the South Asian region must establish a registry of a million potential adult stem cell donors. Globally, the attrition rate in the registries of volunteers, due to lack of commitment, age, disease, and nontraceability at the time of need, is a challenge. The status of the registry in the region looks like the following:
- Currently, in India, five registries and one active public cord blood bank exist with a combined strength of registered adult donors of 350,000 and 6000 fully HLA-typed CBUs. When the registry size increases to 1 million, approximately 60% of the patients will find a matching donor. Unfortunately, most of the Indian donors enrolled in the initial phases belong to the “directed donors'” category. They were recruited during camps and drives for the specific patient (friend or relative) and their commitment to be a donor for anyone else is questionable. No other country in the South Asian region has a bone marrow donor registry. Cost-effective accurate HLA typing of the highest possible resolution of the population is an important factor and the region should have its own facility instead of dependence on the other parts of the world. Such a laboratory will also facilitate research and development in the field of the evolving personal medicine and ensure affordable health care for the ethnic populations of the region. Understanding the regional HLA haplotype diversity could guide registry growth and help more patients find a match.
Lack of standardization of cost and quality
Like the blood transfusion services, the registries are fragmented and the cost varies anywhere between INR 3 lakhs and 10 lakhs (USD 5000–15,000) for the cell product of the same quantity and quality. In addition, there is a compelling need to follow the global standards and to make the product available in a manner similar to nonremunerated voluntary blood donation.
Currently, over fifty transplant centers in India are performing <200 allogenic transplants every year. With varying levels of competence and expertise, the outcome of allogenic transplantation from different centers is not uniform. What the region needs is a network of adequate numbers of excellent facilities managed by highly competent professionals. Such a move will bring down the cost of transplant to enable more patients access the treatment.
Quick and affordable access to matching donor units and affordability of cost of transplant continue to remain the barriers to a hope for the cure of South Asian patients.
| Solutions to Challenges|| |
Availability and affordability must be the goals for a successful HSC transplant program in the region.
To achieve this, the member countries of the South Asian Association for Regional Cooperation should establish a regional registry of a million committed HSC donors and an inventory of a minimum of 100,000 donated CBUs as a readily available resource.
Enrolling committed voluntary donors
With over 27.5% of population in the age group of 15–34 years and over 20 million births a year in India alone (http://www.censusindia.gov.in/), there should not be any difficulty in making this possible, particularly if funding from the respective governments is available.
Recruitment of committed young people as donors, who could be traced at the time of need, is crucial to the success of the program. Apart from recruiting from the general population, one needs to think of converting committed blood donors as potential adult HSC donors. Hence, working together with blood donor organizations and blood banks across South Asia will help building a robust registry with committed donors from diverse linguistic populations.
Standardizing human leukocyte antigen typing method
Reliable high-resolution HLA typing of the donors using the contemporary technology is critical to the long-term success of the program. Next-generation sequencing (NGS)-based whole-gene HLA typing to international standards has become available in most countries including India, and the need to outsource DNA material to the “developed” world can be obviated. In addition, considering the future growth and less dependency, it is necessary to build a pool of competent human resource in the region.
Standards and accreditation
There is no need to reinvent standards. We could adopt the WMDA standards for adult stem cell registries and the NETCORD–FACT standards for public cord blood banking. Similarly, the standards for accreditation can be adopted from agencies such as European Federation for Immunogenetics or American Society for Histocompatibility and Immunogenetics. Accreditation within 3 years of operations must be made mandatory.
Cost of product and transplantation
Standardizing cost across the following three areas needs immediate attention.
- The cost of a unit of PBSC varies from INR 100,000 for cord (USD 1500) to INR 1,000,000 (USD 15,000) per unit. Like blood components, there is a compelling need for immediate rationalization of the processing cost of HSC unit from an adult donor or CBU to discourage profiteering but ensure sustainability. The ideal cost to sustain the program will be around INR 300,000 (USD 5000)
- There is also a need to standardize the cost of high-resolution HLA typing to make it affordable. It is imperative that the most recent technology like NGS must be used for HLA typing. Consolidation of HLA typing by the same technology in three or four regional typing facilities will ensure high-quality typing, proper control of the cost due to volume of work involved, and use of the automation.
- It is important to bring down the overall cost of transplantation and follow-up strategy. According to the Indian Stem Cell Transplant Registry, an organization committed to the science of HSC transplantation in India, the country has fifty transplant centres. The current cost varies from center to center and the type of transplant anywhere between INR 500,000 (USD 8000) and INR 5,000,000 (USD 80,000). Large facilities under public–private partnership model and elimination of the government taxes for the consumables will bring down the cost further, at least to half of the present cost.
| Conclusion|| |
When a large registry becomes a reality, increasing access to matching donor units will become possible. This demand along with the support of the governments of the region will help lowering the overall cost of treatment. This alone will be the harbinger of hope for the patients with potentially curable diseases in this region.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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