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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 1  |  Page : 84-87

Turn around time in matched unrelated donor search workup national versus international registries: Retrospective study


Gene Bandhu, New Delhi, India

Date of Submission12-Nov-2020
Date of Acceptance07-Feb-2021
Date of Web Publication31-Mar-2022

Correspondence Address:
Dr. Vikash Chandra Mishra
Gene Bandhu, South Extension Part-II, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_143_20

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  Abstract 


Background: Timeline is a key factor for hematopoietic stem cell transplant (HSCT) recipient. HSCT by matched unrelated donor (MUD) is a standard definitive therapeutic approach for many hematological disorders which are not amenable to chemotherapy and other conventional treatment. Aims and Objectives: The aim of the present study was to compare the turnaround time (TAT) involved in completion of MUD HSCT workup from an Indian registry (Genebandhu) with international registries. Materials and Methods: On receipt of pre-transplant matching request through a transplant physician, patient's human leukocyte antigen (HLA) type was entered in both Genebandhu and World Marrow Donor Association search tool for initiating a “search.” The software gave the descending order of the best possible matches by performing computational analysis. The search result was considered a “match” when potential 10/10 HLA match was found. The average TAT was calculated in the middle of search request and HLA confirmatory typing (CT) and infectious disease marker (IDM). Further, TAT was also determined between the infusion of harvested stem cell product and CT and IDM. At last, the total time engaged in completion of each MUD HSCT workup was determined and compared in national versus international registries. Results: The average TAT involved in between search request and CT and IDM was 71 days in case of global registry and 67 days in case of Genebandhu. Similarly, the average TAT involved between infusion of harvested cell product and CT and IDM testing in case of donor identified in global stem cell registry was 65 days whereas 45 days in case of Genebandhu. At last, the average time associated with the finishing of a MUD workup was 136 days in case of global registry, whereas 112 days in the case of Genebandhu at P ≤ 0.05 with a 95% confidence interval. Conclusion: To conclude, the average TAT obtained through this study clearly demonstrates the advantages in terms of donor availability for MUD HSCT through the national registry.

Keywords: Genebandhu, hematopoietic stem cell transplant, matched unrelated donor, stem cell registry


How to cite this article:
Mishra VC, Dey N, Bhardwaj AK, Chandra D, Anthwal A, Raina V. Turn around time in matched unrelated donor search workup national versus international registries: Retrospective study. Indian J Transplant 2022;16:84-7

How to cite this URL:
Mishra VC, Dey N, Bhardwaj AK, Chandra D, Anthwal A, Raina V. Turn around time in matched unrelated donor search workup national versus international registries: Retrospective study. Indian J Transplant [serial online] 2022 [cited 2022 May 25];16:84-7. Available from: https://www.ijtonline.in/text.asp?2022/16/1/84/342429




  Introduction Top


HSCT is a standard therapeutic strategy for many hematological disorders such as bone marrow failures syndromes and metabolic diseases.[1],[2] The probability to get human leukocyte antigen (HLA) identity between two siblings is only 25%.[3] Hence, remaining 75% depends upon some unrelated donor known as MUD. More than 35 million donors registered as MUD across the globe and provide stem cells to patients in case of unavailability of matched-related donor (MRD).[4],[5] Among these, India has a scarce representation of only 0.35 million donors. In 1973 the first successful MUD HSCT was performed in New York for a young boy with congenital immunodeficiency. At present, more than 5,000 MUD hematopoietic stem cell transplant (HSCT) are performed in the United States of America (USA) and more than 10,000 worldwide every year. Approximately half of all allogeneic transplants in the USA are performed from unrelated donors.[6] The number of MUD HSCT are increased in India from the last few years but still exact numbers of MUD HSCT are not available.[7] There are seven major steps involved in the MUD HSCT and the time spent during all the steps varies from one to several days depending on donor availability, comfort, and most importantly the country.[8] A report published recently suggested that the MUD search and harvest of stem cell product usually take much longer (on average 3-4 months) than that of an MRD (1 month).[9] We report here for the first time the comparison of TAT involved in MUD HSCT from the work up assisted by Genebandhu[10] and global donor data pool.


  Materials and Methods Top


We performed a retrospective comparative analysis of all the MUD HSCT workup assisted by Genebandhu for 7 years (May 2012-June 2019). We have received preliminary donor search request from different transplant center across India and foreign registry. MUD search was performed both in Genebadhu donor data pool as well as in World Marrow Donor Association (WMDA) search tool. Prometheus was used for search in Genebandhu donor data pool, a specialized information system developed by Steiner Ltd for the operational activity of stem cell donor registries and maintaining HLA database.[11] WMDA search tool was used for searching a donor in any exiting registries as all the donor data are interlinked here.[12] Once search was finished, the preliminary donor search report has been shared with respective transplant physician or foreign registry (in case search request from foreign registry). After selecting the most suitable donor by transplant physician, the procedure moved ahead with workup for hematopoietic stem cells (HSC) collection. Workup includes HLA confirmatory typing (CT) and infectious disease marker (IDM), granulocyte colony-stimulating factor (GCSF) injections, collection of hematopoietic stem cells (HSC), transportation of collected stem cell from donor center to transplant center, and finally infusion to the patient.[8] The average TAT was tallied between search request and HLA CT and IDM for each of the workup. Moreover, TAT was likewise determined between harvested stem cell prodcuct and CT and IDM. Finally, the total time engaged in the completion of each MUD HSCT workup was looked and compared in national versus international registries in Microsoft excel 2010.

Statistical analysis

The average TAT involved between infusion of harvested cell product, CT and IDM testing and entire MUD workup in case of donor identified in global vs national stem cell registry were estimated by using Microsoft excel. Z-score test was used to see the statistical significance between donors identified in global registry compared to Genebandhu (national) donor. A P < 0.05 was considered statistically significant with 95% confidence interval.

Declaration of participant consent

The consent has been taken for participation in the study and for publication. All participants were aware that the names, initials, and photographs would not be published and all standard protocols will be followed to hide their identity.

Ethics statement

It was a retrospective analysis and hence, EC clearance was not needed. The study was carried out as per the declaration of Helsinki. The procedure was carried out in accordance with the Declaration of Helsinki and International Council for Harmonization-Good Clinical Practice (ICH-GCP).


  Results Top


In the period between May 2012 and June 2019, we have assisted 25 MUD HSCT workup. Out of these 14 [Table 1] were from global donor data pool and all the patients are from different parts of India. The remaining 11 cases [Table 2] were from Genebandhu stem cell registry. Out of these 11 cases, seven were for Indian patients whereas four cases were of foreign patients. As per the observed result, the average TAT involved in between search request and CT and IDM was 71 days in case of global registry and 67 days in case of Genebandhu. Similarly, average TAT involved between infusion of harvested cell product and CT and IDM testing in case of donor identified in global donor data pool was 65 days whereas 45 days in case of Genebandhu donor (national registry). At the P ≤ 0.05 with 95% confidence interval, the average mean of total days involved in the completion of the workup was 136 (days) in cases of global registry compared to Genebandhu donor where it was 112 (days). The overall comparison of average TAT in MUD HSCT workup International registries versus National (Genebandhu) is represented in [Figure 1].
Table 1: Representing timeline involved in matched unrelated donor availability from global registry

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Table 2: Representing time line involved in matched unrelated donor availability from Genebandhu registry

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Figure 1: Comparison of average turnaround time in matched unrelated donor hematopoietic stem cell transplant workup international registries versus Genebandhu

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  Discussion Top


The average time obtained through this study clearly demonstrates the advantages in terms of donor availability and turnaround time (TAT) for MUD HSCT through the national registry. Moreover, it will also result in cost reduction because if donor is from global registry then the patient have to pay huge additional amount compared to the national donor due to currency fluctuations, transportation, etc.[13],[14] Furthermore, there are several other factors which may play a crtical role in time taken for MUD HSCT workup like patient condition, donor availability, donor physical fitness, and most importantly the cost. There were cases in the list where the patient took long time to arrange money after the preliminary donor search request and workup got delayed. Some cases among these were delayed due to the unavailability of donor at the time of request. Sometimes, it has been observed that matched unrelated donor (MUD) donor did not turned up on time, and patients may develop progressive disease or become medically unfit for HSCT while waiting for a MUD. Hence, the MUD r retention and tracing are among the list of tough task for a stem cell registry and it plays an important role in MUD HSCT workup.[15] Therefore, dedicated donor counseling and committed staff willing to understand the problem and exploring the best possible way to make MUD understand the need for the issue is required during the voluntary stem cell donor registration. Several approaches such as welcomed mail, birthday wishes, telephonic conversation after every 6 months to check availability, willingness, and current health status may be adopted for donor retention by stem cell registry Additionally monthly newsletter is also a good option and shared on a monthly basis to interact with every registered MUD.

As per observations by Pedala et al. urgent time to HSCT by 90% of physicians and 87% of co-ordinators participated in the study was within 4–6 weeks (30–42 days) of search initiation.[16] Furthermore, if there is a higher disease risk index HSCT urgency was considered more urgent by the participant observation. In our study, the urgent time/TAT was about 45 days in national registry (Genebandhu) while for international registry same was about 65 days. This showcasing the importance of retaining national registry for timely intervention of all the patients.

The present report illustrates that time is an important and vital factor for any MUD HSCT for a recipient. Here, it is also demonstrated that there is a need of a larger national voluntary stem cell donor database. Therefore to achieve this, significant efforts are required to enhance MUD recruitment camps and ultimately the numbers to reduce the TAT as well cost and thus, the chances of saving many vital lives are increased by multiple folds.

Considering the issues, benefits, and limitations of the stem cell registry, possibly the algorithm for donor retention should be in the order; welcome mail > birthday/Marriage anniversary wishes > new year greetings > telephonic conversation after every 6 months > share newsletter (monthly)


  Conclusion Top


The average TAT obtained through this study clearly demonstrates the advantages in terms of donor availability for MUD HSCT workup through the national registry. There are seven major steps which are mandatory and standard norm for MUD HSCT work up and follow all across the globe. Once MUD is identified, the first and most important thing to collect the fresh sample of matched donor to reconfirm the HLA typing knows as CT as well as IDM test. Matched MUD should be negative for IDM to move ahead with HSCT workup for hematopoietic stem cell. After the CT and IDM, donor workup gets started which includes whole body checkup and administration of GCSF injections for 4–5 days and then the collection of hematopoietic stem cell. Hence, it is important for everyone who are involved in this workup (family members and transplant team) to understand that time involved in this entire process of MUD HSCT varies from patient to patient and most importantly depends upon donor availability whether it is from national data base or from foreign registry. Though numbers of MUD workups assisted by Genebandhu are not big enough and hence, the present report opens the need for further detailed analysis with a larger number of MUD HSCT workups. Such information on a bigger size will be a deciding tool for MUD HSCT especially in the era where number of haploidentical transplants is increasing day by day.

Limitations

The study was limited by small sample size and opens the need for further detailed analysis with bigger sample size.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Riezzo I, Pascale N, La Russa R, Liso A, Salerno M, Turillazzi E. Donor selection for allogenic hemopoietic stem cell transplantation: Clinical and ethical considerations. Stem Cells Int 2017;2017:1-11.  Back to cited text no. 1
    
2.
Henig I, Zuckerman T. Hematopoietic stem cell transplantation-50 years of evolution and future perspectives. Rambam Maimonides Med J 2014;5:e0028.  Back to cited text no. 2
    
3.
Appelbaum FR. The use of bone marrow and peripheral blood stem cell transplantation in the treatment of cancer. CA-Cancer J Clic1996;46:142-64.  Back to cited text no. 3
    
4.
Hurley CK, Oudshoorn M, Setterholm M. Donor registries and search strategies. Methods Mol Biol 2012;882:531-47.  Back to cited text no. 4
    
5.
Available from: https://statistics.wmda.info. [Last accessed on 2020 Nov 11].  Back to cited text no. 5
    
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7.
Raut SS. Autologus stem cell transplantation for cancers: India: 2017. J Blood Disord Transfus 2017;8:2.  Back to cited text no. 7
    
8.
Mishra VC, Tiwari AK, Raina V, Sharma G. Timelines, an important tool for matched unrelated donor stem cell transplant: A case report and review of literature. Indian J Transplant 2018;12:205.  Back to cited text no. 8
  [Full text]  
9.
Ciurea SO, Bittencourt MCB, Milton DR, Cao K, Kongtim P, Rondon G, et al. Is a matched unrelated donor search needed for all allogeneic transplant candidates? Blood Adv 2018;2:2254-61.  Back to cited text no. 9
    
10.
Available from: http://genebandhu.in/. [Last accessed on 2020 Nov 11].  Back to cited text no. 10
    
11.
Available from: https://search.wmda.info. [Last accessed on 2020 Nov 11].  Back to cited text no. 11
    
12.
Available from: http://www.hlasoft.com/index.php/prometheus-software. [Last accessed on 2018 Nov 11].  Back to cited text no. 12
    
13.
Sharma SK, Choudhary D, Gupta N, Dhamija M, Khandelwal V, Kharya G, et al. Cost of hematopoietic stem cell transplantation in India. Mediterr J Hematol Infect Dis 2014;6:e2014046.  Back to cited text no. 13
    
14.
van Agthoven M, Groot MT, Verdonck LF, Löwenberg B, Schattenberg AV, Oudshoorn M, et al. Cost analysis of HLA-identical sibling and voluntary unrelated allogeneic bone marrow and peripheral blood stem cell transplantation in adults with acute myelocytic leukaemia or acute lymphoblastic leukaemia. Bone Marrow Transplant 2002;30:243-51.  Back to cited text no. 14
    
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Jervis S, Wood K, Logan A, Lee H, Poulton K. Unrelated haematopoietic stem cell donor attrition rate: A manchester experience. Int J Immunogen 2013;40:411-2.  Back to cited text no. 15
    
16.
Pidala J, Mupfudze TG, Payton T, Barker J, Perales MA, Shaw BE, et al. Urgent time to allogeneic hematopoietic cell transplantation: A national survey of transplant physicians and unrelated donor search coordinators facilitated by the histocompatibility advisory group to the national marrow donor program. Biol Blood Marrow Transplant 2019;25:2501-6.  Back to cited text no. 16
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2]



 

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