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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 4  |  Page : 405-410

Issues faced by a resource-constrained stem cell donor registry and impact of coronavirus disease 2019 on their functioning: A 9-year observational study from a single registry in India


1 Chimera Transplant Research Foundation, South Extension Part-II, Masjid Moth; Genebandhu, South Extension Part-II, New Delhi; Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India
2 Department of Transfusion Medicine, Medanta the Medicity, Gurgaon, Haryana, India
3 Genebandhu, South Extension Part-II, New Delhi, India
4 Chimera Transplant Research Foundation, South Extension Part-II, Masjid Moth; Genebandhu, South Extension Part-II, New Delhi, India
5 Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University Uttar Pradesh; Amity Center for Cancer Epidemiology and Cancer Research, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India

Date of Submission02-Mar-2022
Date of Acceptance06-Sep-2022
Date of Web Publication30-Dec-2022

Correspondence Address:
Dr. Girish Sharma
Amity Center for Cancer Epidemiology and Cancer Research, Amity University Uttar Pradesh, Sector -125, Noida, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_30_22

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  Abstract 


Background: Allogeneic hematopoietic stem cell transplantation activity is growing globally as one of the curative treatment options for many hematological diseases. A stem cell transplant registry plays an important role in such treatment. Setting up a functional stem cell donor registry is quite challenging with several issues such as resources, donor recruitment, donor attrition, ethnicity, lack of support, and impact of coronavirus disease 2019 (COVID-19). Aim: The aim of the current study was to present the experience of a resource-constrained registry in India as well as the effect of COVID-19 on its operations. Settings and Design: The present study was a descriptive study which was designed to study the functioning of a resource-constrained registry from north India. Materials and Methods: The study data for the period of 2012–2020 pertaining to donor recruitment, number of searches, number of matched donors, number of transplants performed, and donor attrition was collected from the registry software “Prometheus.” Statistical Analysis: Descriptive statistics such as frequency and percentage was used. Results: During the past 9 years of operation, the registry has faced several issues pertaining to lack of funds, donor recruitment, donor attrition, and COVID-19 has exacerbated their pain points significantly. The registry has recruited a total of 20,093 donors, of which only 7794 have been human leukocyte antigen typed, with the remaining samples awaiting funding. Out of this small number of typed donors, registry has performed 15 matched unrelated donor transplants for Indian and international patients. As a result of COVID-19, donor attrition was on the rise and showed a peak in 2020. During the year 2020, the number of searches, donor recruitment camps, and donors all decreased considerably. Conclusion: The establishment and operation of a stem cell transplant registry necessitate extensive planning and resources. The resource-constrained registries face a number of issues pertaining to effective functioning and future developments. The external support and awareness for the cause can help minimize the pain points of these registries.

Keywords: Coronavirus disease 2019, Donor, India, issues, stem cell registry


How to cite this article:
Solanki H, Tiwari AK, Dey N, Raina V, Sharma G. Issues faced by a resource-constrained stem cell donor registry and impact of coronavirus disease 2019 on their functioning: A 9-year observational study from a single registry in India. Indian J Transplant 2022;16:405-10

How to cite this URL:
Solanki H, Tiwari AK, Dey N, Raina V, Sharma G. Issues faced by a resource-constrained stem cell donor registry and impact of coronavirus disease 2019 on their functioning: A 9-year observational study from a single registry in India. Indian J Transplant [serial online] 2022 [cited 2023 Feb 3];16:405-10. Available from: https://www.ijtonline.in/text.asp?2022/16/4/405/364618




  Introduction Top


A stem cell transplant (also known as bone marrow transplant) is the definite treatment option for many patients with certain hematological malignancies and even few benign hematological disorders.[1] In order to get easy access to healthy adult hematopoietic stem cells that are procured from healthy voluntary donors worldwide, a stem cell registry is set up. It is a databank of voluntary stem cell donors and is usually affiliated to the World Marrow Donors Association (WMDA) database, which is then available for the patients, around the world, seeking a human leukocyte antigen (HLA)-matched unrelated donor (MUD), mostly sought when there is no immediate family donor. The primary motive of a stem cell registry is to help and connect people to come together for a humanitarian cause and setting it up requires an initial investment, constant financial support, and large multitude of willing donors coming forward perennially for such righteous cause.[2]

Possibly, the first ideation of a stem cell registry was a brainchild of Shirley Nolan in 1974 who founded a registry in England, when his own son was in a dire need of a MUD transplant.[3] Currently, in February 2022, the global WMDA database contained 38,998,026 donors and 804,125 cord blood units from 100 different registries in 55 different countries, in which the Indian donor share was approximately 0.55 million from five functional registries.[2] The probability of finding an HLA-matched donor for an Indian patient in global database is very low as they hardly get represented in international registries. Since the probability of finding matched donor depends on the ethnicity and HLA haplotype frequency of that population, establishment, and functioning of local registries with local representative donor data pool is very important.[4],[5] In a developing country like India, stem cell registries face a lot of challenges pertaining to financial resources, donor recruitment, HLA typing, and donor retention. The onset of coronavirus disease 2019 (COVID-19) has further exacerbated the pain points of these registries by halting or delaying most of its processes. In the current article, we present our 9 years (2012–2020) of experience, as well as the pain points of a resource-constrained stem cell registry and the effects of COVID-19 on its functioning.


  Materials and Methods Top


Registry and matched unrelated donor

A patient with hematological disorder going for hematopoietic stem cell transplantation needs an HLA-matched donor. If it is not found in the family, MUD is searched across the global donor data pool. A registry is “an organization responsible for the coordination for the search for hematopoietic progenitor cells (HPC) from donors (including cord blood) unrelated to the potential recipient” (WMDA International Standards 2017).[2]

A registry searches for a MUD match for a patient upon the “request” from a transplant center (TC). TC is a medical setup where the transplant of the patient takes place. A registry can recruit the donors through donor center (DC) which is normally seen in registries with large database in developed countries. A DC can be a blood bank or transfusion unit responsible for recruitment, contacting, medical examination, harvest of stem cells, follow-up from the donor, and transporting the cells to the TC. DC shares the donor information with the registry and then registry up-list the donor in the database. On the other hand, in some of countries and in several resource-constrained registries the DC activities are performed by the registry itself [Figure 1].
Figure 1: Voluntary stem cell donor registry set-up and function flow-chart. HLA: Human leukocyte antigen, WMDA: World Marrow Donors Association, DC: Donor center, TC: Transplant center, MUD: Matched unrelated donor

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Study data

The current study was performed at a voluntary stem cell donor registry from north India. The study data for 2012–2020 pertaining to donor recruitment, typed and untyped donors, number of searches received, number of matched donors, number of transplants performed, and donor attrition were collected from the registry software “Prometheus” developed by Steiner Ltd. (Czech Republic), which is an information system for stem cell donor registries used globally, covering all the registry operations such as donor and patient data management, WMDA HLA export, donor searches, finances, transplant work-up, and follow-up.[6] Descriptive statistics such as frequency and percentage was used for analysis.

Statistical analysis

Descriptive statistics such as frequency and percentage were used to compare the data reported in last 9 years. The statistical analysis was performed using Microsoft Excel 2010 (Microsoft Corporation, Redmond, Washington, United States).

Declaration of patient consent

The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names and initials would not be published, and all standard protocols will be followed to conceal their identity.

Ethics statement

Ethical approval was obtained from the Institutional Ethics Committee for Health-Related Research (ECG001). The study has been performed in accordance with ethical committee and the ethical standards as laid down in the 1964 Declaration of Helsinki as revised in 2013.


  Results and Discussion Top


Our main aim was to present the 9-year of experience of a resource-constrained registry and highlight their pain points and effect of COVID-19 pandemic. Indian registries being from a developing country have their own issues pertaining to its efficient functioning.

Lack of funds

A registry like any other medical set up requires investment for office premises, information technology infrastructure including server(s), hardware, operating systems, software, and many a time, recurring proprietary software-fee and insurance fee (for staff, MUD donors, and patients). From its establishment to its functioning, funding plays a crucial role. One of the biggest constraints comes in the form of a lack of finances when it comes to HLA typing. With no support from the government, each HLA typing is difficult. There are times when it is impossible to HLA type all the samples collected from a drive as there is a financial void, therefore the samples are archived and a financial help is waited on to type these samples. It is more appalling, as they could be a potential “match” for one of the patients searching for MUD, while the sample is “stored and not-typed.” In our registry, the total number of typed donors registered at WMDA was 7794 and remaining of the 10,351 collected samples were untyped and stored awaiting funds for typing [Table 1].
Table 1: Patients and donor data from the registry (2012–2020)

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Funding is also necessary to cover up for the donor recruitment drive in the form of travel, compensation for employees, and materials such as registration forms, pamphlets, and banners. The donor recruitment drives are held across different locations. Besides these costs, there are perpetual costs such as continuous educational training of staff and their participation in national and international conferences.

Being a medical establishment, a registry engages a number of professionals, both skilled and semi-skilled in several disciplines, medical, finance, communication, hospitality, legal, etc. to name a few. There are specific key positions of medical director, search coordinator, donor coordinators, HLA experts, etc., The coordinators should be trained in accordance with WMDA recommendations relating to their specific area of expertise related to MUD transplants.

Donor recruitment/counseling

Approximately 2 million voluntary donors are registered to WMDA by worldwide registries each year.[7] The main aim of a registry is to increase the donor database by recruiting as many donors as possible and to acquaint the donors with the whole process as it is a voluntary and altruistic act and donors can withdraw their name at any step of the donation. However, donor counseling and recruitment are one of the major challenges for a stem cell registry, especially in countries like India. Donor counseling is done at two stages; during registration of the donor and later when the donor is found to be a “match” for the patient. It has been widely observed that despite education at the time of recruitment, the donors often lack a comprehensive “view” of the whole process of HPC MUD transplant. There have been several cases, when the donor withdrew consent just before actual HPC harvest, causing demotivation to the personnel at the registry and its efforts to support patients and their physicians. In some cases, many donors think of it as equivalent to fetal chord stem cell therapy. Further, many personnel recruiting donors face issues while asking questions related to ethnicity, race, and medical history. Some donors do not put up well with such queries while some hide their medical history. This creates serious impediments in the donor recruitment drive as the quality of donors gets compromised. Moreover, it is even more difficult to convince people when there are no monetary benefits involved.

Drives are conducted at educational institutes, places of worship/spiritual centers, corporate offices, family and community drives, and nongovernment organizations. Awareness campaigns at these places help in reaching the target audience and with the help of “right aids” at right places, one can hope to garner larger number of donor registrations. Language, which is sometimes, a barrier at certain places, can be overcome by recruiting “local volunteers” speaking vernacular language. However, that also calls for better training of such local volunteers so that they can represent the registry better. The registry has recruited a total of 20,093 donors by organizing 248 camps across India during this period. The number of camps and donors has decreased significantly in the year 2020 due to the COVID-19 effect by 92.30% and 97% respectively compared to the previous year 2019 [Table 1].

The “second round” and a more detailed donor counseling is required when a donor is found a match to a patient. The donor is informed about the entire HPC harvest procedure, its benefits to the intended recipient and the risks, including possible death to the recipient, if the donor withdraws after the recipient's conditioning therapy has begun.

The medical assessment of the donor and the possible side effects of donation that are enumerated during consenting may make the donor apprehensive. Some of the donors are not willing to disclose their medical history and therefore, do not “proceed further.” Family pressure has often been a big cause in donors “backing out” during this process. In the current study, the registry has received a total of 1514 searches till December 2020 which also got decreased significantly in the year 2020 [Table 1]. A total of 114 matches were found for the hematological disorder patients, and 15 MUD transplants were performed from the registry's small database. Out of these 15 transplants, 60% of the MUDs were performed for Indian patients and rest 40% were for the patients of Germany, Canada, the United States of America (USA), and the United Kingdom during the years 2014–2020.

Donor retention

Another challenge that a voluntary stem cell registry faces is the retention of the registered donors. Considering the fact when a donor quits from the database does not only cause financial loss to the registry but also diminishes the chances of a patient for whom such donation could be a “gift of life.”

Retention of registered donor is not an easy task due to the vibrant nature of the socio-economic environment and the human factors involved. Registries face a “donor withdrawal,” sometimes immediately after the recruitment, or when the recruited donor discusses with the family and relatives and they do not agree with the idea of being a MUD donor, or because of change of address and/or contact number without updating of such information with the registries. Few of the donors quit because of some health issues. A study on USA donors revealed that psychological characteristics contribute more to donor attrition than demographic characteristics of donors and an effective counseling and regular communication is required to minimize the attrition rate.[8] Following are the ways which a registry follow-up to keep the donor active in the database.

  • Dedicated donor counseling and committed staff
  • Welcome mail upon recruitment of the donor
  • Birthday wishes
  • Telephonic conversation every 6 months and confirming their address and contact details
  • Sending the donor monthly newsletter


In the present study, the donor attrition showed an increasing trend every year from 2012 to 2020. Out of the total donors recruited, 9.7% of the donors have withdrawn their registration or did not want to be a donor for any matched patient. Moreover, 35 donors withdrew their registration after being a match to a patient [Table 1].

Lack of incentives for donor(s)

A donor apart from his valuable donation of stem cells also devotes a lot of his personal time in the process. Right from his/her medical assessment, stem cell harvest to postdonation rest, a lot of time is spent by the donor. It has been observed that many times there is a long distance between a donor and the medical center. Therefore, it takes a lot of time to get the donors at the center for which they are not even paid by their employers as stem cell donation does not get defined as “paid leaves.” Thus, the fear of loss of leaves or sometimes, even jobs, deter the donors.

No support from media

In this digital age, social media can play a huge role in donor drives. Any support cropping on social media can be well harnessed in conducting drives, encouraging people to come up and donate. Moreover, since it has a huge influence on the lives of people, a delicately devised strategy to invoke humane values in people by creating awareness through various channels can help mobilize the much-needed support to the already ailing registries in dire need of both donors and finances. Furthermore, since registries cannot afford to hire ambassadors for its publicity, social media can be used to connect to such celebrities who are willing to donate their time for such a noble cause so as to attract more and more people and garner public support. Currently, in India, no such support from media is available which makes the aim of such registries even more difficult.

Increased human leukocyte antigen diversity in data pool

HLA is the most polymorphic region of human genome with 32,897 alleles registered at The international ImMunoGeneTics information system (IMGT) database.[9] The likelihood of getting a MUD depends on the ethnicity and HLA haplotypes of the patients. The chances of getting an 8/8 match for whites (~75%) were much higher than a non-white (~16%) due to greater representation of Caucasians in global database.[10] Furthermore, Japan having a homogenous population and less polymorphic HLA types has 96% chances of getting 8/8 HLA-matched donors.[11] Furthermore, India when compared to the rest of the world possessing more than a third of novel and unique HLA types, and with a heterogeneous population, greater genetic diversity and highly polymorphic HLA genes not only require large number of stem cell donors but also greater genetic diversity especially the ethnic minority groups in the donor HLA.[12] This becomes a bigger challenge for the registries as there is no centralized database in our country and it is always unknown that how many new voluntary stem cell donors should be added to achieve adequate representation of different HLA phenotypes in the global donor data pool.

Impact of coronavirus disease 2019

COVID-19 has emerged as a threat to the voluntary stem cell donor registries and their functioning. [Figure 2] shows the month-wise impact of COVID-19 on the functioning of the registry. The registry was not able to organize any camp from March 20 to December 20. During this period with the help of social media only 12 donors were recruited. The number of searches decreased considerably especially during the full lockdown period, later there was a slight increase in the search requests but that was not optimum. Registry saw the biggest donor attrition in 2020 where total of 748 donors withdrew their name as a voluntary donor.
Figure 2: Impact of COVID-19 on registry functioning from January, 20 to December, 20

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The annual increase in the number of voluntary stem donor from 4.8 million to approximately 28 million during 1997–2016 would not have been possible, without the enlargement of the unrelated stem cell donor registries through donor recruitment camps and proper counseling.[2] Coronavirus spread has slowed down or halted the process of donor recruitment. The group swabbing is not possible and therefore not done as per the guidelines of health care authorities and COVID-19 guidelines.[2] It has become impossible to arrange big drives at a venue because of guidelines on maintaining physical distances. Everything in India was virtually shut down for almost 3 months and there after only essential activities resumed in a phase-wise manner. With the cases climbing over 42 million mark, India currently stands at second spot.[13] Since the world is running virtually now, the registries are also trying to engage donors in online drives through social media. However, little has been achieved so far. Moreover, online recruitment has its own pros and cons. Sometimes, the donor resides in a containment zone and this makes it difficult to reach out to him/her. The main issue of online recruitment is that it is limited to a certain age group and social structure. You cannot reach to rural population and people who cannot use social media but are otherwise potential donors.

The COVID-19 has not only impacted the current recruitment camps as it seems like in future when the government would permit such gatherings, people may still not be willing to participate fearing higher risk of disease transmission. At the same time, the safety and security of the registry staff will also remain an added concern in large public gatherings.

Donor selection has been impacted immensely worldwide and the guidelines issued by WMDA makes the donor selection for the donation process much more difficult. The recommendations include donor deferral for different period.[2],[14] The donor selection and then procuring the stem cells is also uncertain as the donor could get infected during the process, or if the apheresis center staff is found positive or the logistic difficulties at the last moment due to the travel restriction across the border. The stem cell registry is a part of global networking of voluntary stem cell donors. As discussed earlier the poor representation of Indians (or Asians), in the data pool makes the chances of finding a matched donor less likely for an Indian patient. With borders closing and flights being canceled, it has become more challenging to get stem cells from international donors into India. This means that patients in India are becoming more dependent on Indian donors but with a smaller Indian donor database, it is impossible to find a MUD match compared to other countries who are relying on national donors. Apart from the transportation, the safety of the stem cell product coming from and going from a country with a higher COVID-19 case-load is also a concern.

Currently, a major issue surrounds the already sick cancer patients. Corona has added to their woes as the availability of a donor has been greatly reduced. Especially in India, when even the presence of matched donor but inability to donate due to COVID-19 has exasperated the patients and registry. With the ambiguity surrounding corona, more and more people are pulling out their names from registries. The thought of donating stem cells seems risky as nobody wants to be confined to a hospital for 3–4 days (physical examination and donation) in an already alarming and inhospitable situation like today.

Limitation

Data from other such registries will further validate the results.


  Conclusion Top


We can say that local voluntary stem cell donor registries are very important to increase the chances of getting a MUD match for the patients in need, yet these resource-constrained registries are facing several issues and COVID-19 has escalated them immensely. The lack of support and ongoing crisis of pandemic can pose a threat to their existence.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Copelan EA. Hematopoietic stem-cell transplantation. N Engl J Med 2006;354:1813-26.  Back to cited text no. 1
    
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Cleaver SA. The Anthony Nolan Research Centre. Bone Marrow Transplant 1993;11 Suppl 1:38-40.  Back to cited text no. 3
    
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Tiwari AK, Bhati-Kushwaha H, Kukreja P, Mishra VC, Tyagi N, Sharma A, et al. Probability of finding marrow unrelated donor (MUD) for an Indian patient in a multi-national human leukocyte antigen (HLA) registry. Indian J Hematol Blood Transfus 2015;31:186-95.  Back to cited text no. 4
    
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Beatty PG, Mori M, Milford E. Impact of racial genetic polymorphism on the probability of finding an HLA-matched donor. Transplantation 1995;60:778-83.  Back to cited text no. 5
    
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7.
Foeken LM, Green A, Hurley CK, Marry E, Wiegand T, Oudshoorn M, et al. Monitoring the international use of unrelated donors for transplantation: The WMDA annual reports. Bone Marrow Transplant 2010;45:811-8.  Back to cited text no. 7
    
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Switzer GE, Dew MA, Stukas AA, Goycoolea JM, Hegland J, Simmons RG. Factors associated with attrition from a national bone marrow registry. Bone Marrow Transplant 1999;24:313-9.  Back to cited text no. 8
    
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Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med 2014;371:339-48.  Back to cited text no. 10
    
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Saito H, Ito M, Kato S, Kodera Y, Okamoto S, Taniguchi S, et al. The japan marrow donor program, 25 years of experience in achieving 20,000 bone marrow transplantations: Organization structure, activity, and financial basis. Bone Marrow Transplant 2018;53:609-16.  Back to cited text no. 11
    
12.
Jangi S. Problems of creating bone marrow donor registries in emerging economies. BMJ 2013;346:f2976.  Back to cited text no. 12
    
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Available from: https://covid19.who.int/. [Last accessed on 2022 Mar 02].  Back to cited text no. 13
    
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Sahu KK, Siddiqui AD, Cerny J. COVID-19 pandemic and impact on hematopoietic stem cell transplantation. Bone Marrow Transplant 2020;55:2193-5.  Back to cited text no. 14
    


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