Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 1817  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Articlesmenu-bullet Search Instructions Online Submission Subscribe Etcetera Contact
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::  Article in PDF (241 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  References

 Article Access Statistics
    PDF Downloaded17    
    Comments [Add]    
    Cited by others 1    

Recommend this journal


  Table of Contents     
Year : 2021  |  Volume : 67  |  Issue : 4  |  Page : 196-197

Donor-type aplasia after stem cell transplantation in aplastic anaemia: Current understanding and intervention

Former Director, National Institute of Immunohematology, 13 th fl, KEM Hospital Multistorey Building, Parel, Mumbai, Maharashtra, India

Date of Submission20-Jan-2021
Date of Decision11-Mar-2021
Date of Acceptance01-Apr-2021
Date of Web Publication26-Nov-2021

Correspondence Address:
K Ghosh
Former Director, National Institute of Immunohematology, 13 th fl, KEM Hospital Multistorey Building, Parel, Mumbai, Maharashtra
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpgm.JPGM_64_21

Rights and Permissions

How to cite this article:
Ghosh K. Donor-type aplasia after stem cell transplantation in aplastic anaemia: Current understanding and intervention. J Postgrad Med 2021;67:196-7

How to cite this URL:
Ghosh K. Donor-type aplasia after stem cell transplantation in aplastic anaemia: Current understanding and intervention. J Postgrad Med [serial online] 2021 [cited 2023 Jun 7];67:196-7. Available from:

In the current issue of this journal Majumder et al.,[1] have described a case of severe aplastic anaemia who died after successful allogenic stem cell transplantation due to donor-type aplasia (DTA). Secondary marrow aplasia following full donor cell chimerism after allogeneic transplantation in aplastic anaemia is extremely rare amongst Caucasians[2] but reported frequently from southeast Asian countries in 5-18% cases.[3] Data from stem cell transplantation centers in India is meagre.[4] Therein lies the interest in this case report.

Severe aplastic anaemia can be treated preferably by allogeneic stem cell transplantation in young patients if matched sibling (family) donor (MSD) or even matched unrelated donor (MUD) is available. Following transplantation in aplastic anaemia, complications like relapse/refractoriness is an important challenge.

Initially this was described as primary and secondary and was related to immediate rejection of donor cells in primary refractoriness with dire consequences. Secondary refractoriness or relapse used to happen several months and years after transplantation and has been analyzed in great details with reference to donor cell chimerism.[5] Full donor chimerism or stable mixed chimerism was associated with best results and continuous donor cell loss, secondary relapse and refractoriness complicate other types of chimerism.

Most interesting finding in some of the series of transplantation cases in severe aplastic anaemia was DTA. This is intriguing because in these cases more than 90% of marrow cells were still of donor origin though the patient had relapsed to marrow aplasia as described in the case report. Usual techniques like increasing immunosuppression, rituximab therapy and donor lymphocyte infusion do not work in such cases, except re-transplantation with the primary donors stem cells The phenomenon of DTA occurred 1 to 6 years after transplantation and proportion of such cases increased with increased use of fludarabine-based conditioning regimens where cyclophosphamide injection was reduced by 50%. Whether it happens for Indian patients with aplastic anaemia in some frequency is not known. Even in the multicentric study reported with fludarabine-based conditioning from the country[4] at the end of 5 years 75% patients were well so what happened to other 25% patients? Ten years back, DTA was not considered as a serious challenge and hence it has not been studied. But in future it has to be considered seriously in our country.

What is the pathogenesis of DTA? This is not known with any degree of certainty but following conjectures have been made:[6]

  1. After transplantation, the donor stem cells continue to be destroyed over the years leading finally to haemopoietic stem cell deficiency but other cells of donor origin remain.
  2. A small lymphoid clone of recipient origin persists and destroys donor cells. Hence after second conditioning and transplantation this is destroyed and patient recovers.
  3. For DTA a second hit in terms of virus infection e.g., parvovirus, cytomegalovirus and Epstein-Barr virus is required. In some cases of DTA parvovirus infection has been documented.
  4. Finally a lot more is known about immune dysregulatory microenvironment in aplastic anaemia along with destruction of stem cell niche constituted by various types of mesenchymal cells in this condition.[7] Destruction of these niche can lead to DTA.

Is there some predisposition for DTA? It seems more than 40 units of prior blood product transfusion, low number of infused CD34 + ve cells (<3 × 10 6 cells/kg), elderly patient >40 years, fludarabine-based conditioning regime with reduced dose of cyclophosphamide to be more often associated with DTA.[6] There is a need to dissect each of these components operative for production of DTA through culture and co-culture experiments and see if there is loss of CD34 +ve donor cells or haemopoietic differentiation block in these cases.

In the present case DTA occurred after stoppage of cyclosporin. Probably with stoppage of cyclosporine, residual recipient anti-donor clones of lymphocytes proliferated and resulted in immune dysregulation causing DTA. There are reports of eltrombopag reversing DTA.[6] This therapy can be tried in these patients while waiting for second transplantation, or CD34 cell boost from the donor with augmented immunosuppression.

 :: References Top

Majumder A, Misra S, Kumar V. Recurrent aplastic anaemia with donor type aplasia: A rare occurrence in the Indian subcontinent. J Postgrad Med 2021;67:235-7.  Back to cited text no. 1
[PUBMED]  [Full text]  
Eapen M, Davies SM, Ramsay NK. Late graft rejection and second infusion of bone marrow in children with aplastic anaemia. Br J Haematol 1999;104:186-8.  Back to cited text no. 2
Yoshida N, Yagasaki H, Yabe H, Kikuchi A, Kobayashi R, Takahashi Y, et al. Donor type aplasia after bone marrow transplantation in children with aplastic anaemia: A nationwide retrospective study. Blood 2012;120:959.  Back to cited text no. 3
George B, Mathews V, Lakshmi KM, Melinkeri S, Sharma A, Viswabandya A, et al. The use of fludarabine-based conditioning regimen in patients with severe aplastic anemia - A retrospective analysis from three Indian centres. Clin Transplant 2013;27:923-9.  Back to cited text no. 4
Lawler M, McCann SR, Marsh JC, Ljungman P, Hows J, Vandenberghe E, et al. Serial chimerism analysis indicate that mixed haemopoietic chimerism influences the probability of graft rejection and disease recurrence following allogeneic stem cell transplantation (SCT) for severe aplastic anaemia (SAA): Indication for routine assessment of chimerism post SCT for SAA. Br J Haematol 2009;144:933-45.  Back to cited text no. 5
Shaw A, Passweg JR, De La Fuente J, Bajwa R, Stein J, Al-Zaben A, et al. Relapse of aplastic anemia with majority donor chimerism (donor-type aplasia) occurring late after bone marrow transplantation. Biol Blood Marrow Transplant 2020;26:480-5.  Back to cited text no. 6
Medinger M, Drexler B, Lengerke C, Passweg J. Pathogenesis of acquired aplastic anemia and the role of the bone marrow microenvironment. Front Oncol 2018;8:587.  Back to cited text no. 7

This article has been cited by
1 Human Cytomegalovirus Infection of Epithelial Cells Increases SARS-CoV-2 Superinfection by Upregulating the ACE2 Receptor
Marianne R Perera, Edward J D Greenwood, Thomas W M Crozier, Elizabeth G Elder, Janika Schmitt, Colin M Crump, Paul J Lehner, Mark R Wills, John H Sinclair, Stephen Baker, John Bradley, Gordon Dougan, Christoph Hess, Ian Goodfellow, Ravi Gupta, Nathalie Kingston, Paul J Lehner, Paul A Lyons, Nicholas J Matheson, Willem H Owehand, Caroline Saunders, Kenneth G C Smith, Charlotte Summers, James E D Thaventhiran, Mark Toshner, Michael P Weekes, Ashlea Bucke, Jo Calder, Laura Canna, Jason Domingo, Anne Elmer, Stewart Fuller, Julie Harris, Sarah Hewitt, Jane Kennet, Sherly Jose, Jenny Kourampa, Anne Meadows, Criona O’Brien, Jane Price, Cherry Publico, Rebecca Rastall, Carla Ribeiro, Jane Rowlands, Valentina Ruffolo, Hugo Tordesillas, Ben Bullman, Benjamin J Dunmore, Stuart Fawke, Stefan Gräf, Josh Hodgson, Christopher Huang, Kelvin Hunter, Emma Jones, Ekaterina Legchenko, Cecilia Matara, Jennifer Martin, Ciara O’Donnell, Linda Pointon, Nicole Pond, Joy Shih, Rachel Sutcliffe, Tobias Tilly, C
The Journal of Infectious Diseases. 2022;
[Pubmed] | [DOI]


Print this article  Email this article
Online since 12th February '04
© 2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow