Log in

Unmanipulated Stem Cell Boost for Mixed Chimerism in Transfusion Dependent Thalassemia

  • Original Article
  • Published:
Indian Journal of Hematology and Blood Transfusion Aims and scope Submit manuscript

Abstract

Early mixed chimerism (MC) can lead to secondary graft rejection post allogeneic hematopoietic stem cell transplantation in transfusion dependent thalassemia (TDT) patients. Reduction of immunosuppression and donor lymphocyte infusions is the mainstay for treating MC. We report our experience of administering unmanipulated stem cell boost (SCB) in reversing progressive early MC. There were 70 transplants done for 69 TDT patients at our center between September 2005 and January 2020. Mixed chimerism was defined by > 5% recipient cells and the severity was assigned according to the proportion of recipient cells as level 1 =  < 10%, level 2 = 10–25%, level 3 =  > 25%. For patients develo** MC level 2 and 3, we administered unmanipulated SCB and analyzed its safety and efficacy. Out of 70 transplants 7 (10%) had MC level 2 (3/7) and 3 (4/7). These patients received unmanipulated SCB at a median CD34 cell dose of 4.5 × 106/kg (range—3.5 × 106/kg–5.5 × 106/kg). Overall Response (stable MC and/or transfusion independency) to unmanipulated SCB was seen in 5 patients (71.4%). Five patients (71.4%) developed acute graft versus host disease (GVHD) of which 1 patient expired due to severe GVHD. SCB infusion was well tolerated by majority of our patients. The 3 year overall survival and thalassemia free survival was 85.7% (6/7) and 57.1% (4/7) respectively. Timely monitoring of chimerism is important for detecting early MC. Development of acute GVHD is common after administration of unmanipulated SCB and requires vigilance and prompt management. Unmanipulated SCB is a feasible modality for treating progressive MC and salvaging the graft especially in resource-constrained settings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Similar content being viewed by others

References:

  1. Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C et al (1993) Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. New Engl J Med 329:840–844

    Article  CAS  Google Scholar 

  2. Lucarelli G, Andreani M, Angelucci E (2000) The cure of thalassemia by bone marrow transplantation. Blood Rev 16:81–85

    Article  Google Scholar 

  3. Lucarelli G, Gaziev J (2008) Advances in the allogeneic transplantation for thalassemia. Blood Rev 22:53–63

    Article  Google Scholar 

  4. Nesci S, Manna M, Andreani M, Fattorini P, Graziosi G, Lucarelli G (1992) Mixed chimerism in thalassemic patients after bone marrow transplantation. Bone Marrow Transpl 10:143–146

    CAS  Google Scholar 

  5. Manna M, Nesci S, Andreani M, Tonucci P, Lucarelli G (1993) Influence of the conditioning regimens on the incidence of mixed chimerism in thalassemic transplanted patients. Bone Marrow Transpl 12:70–73

    Google Scholar 

  6. Andreani M, Manna M, Lucarelli G, Tonucci P, Agostinelli F, Ripalti M et al (1996) Persistence of mixed chimerism in patients transplanted for treatment of thalassemia. Blood 87:3494–3499

    Article  CAS  Google Scholar 

  7. Andreani M, Nesci S, Lucarelli G, Tonucci P, Rapa S, Angelucci E et al (2000) Long-term survival of ex-thalassemic patients with persistent mixed chimerism after bone marrow transplantation. Bone Marrow Transpl 25:401–404

    Article  CAS  Google Scholar 

  8. Li CK, Chik KW, Tsang KS, Pong H, Shing MM, Yuen PM (2002) Mixed chimerism after bone marrow transplantation for thalassemia major. Haematologica 87:781–782

    PubMed  Google Scholar 

  9. Hsieh MM, Wu CJ, Tisdale JF (2011) In mixed hematopoietic chimerism, the donor red cells win. Haematologica 96:13–15

    Article  Google Scholar 

  10. Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C et al (1990) Bone marrow transplantation in patients with thalassemia. New Engl J Med 322:417–421

    Article  CAS  Google Scholar 

  11. Mathews V, George B, Deotare U, Lakshmi KM, Viswabandya A, Daniel D et al (2007) A new stratification strategy that identifies a subset of class III patients with an adverse prognosis among children with beta thalassemia major undergoing a matched related allogeneic stem cell transplantation. Biol Blood Marrow Transpl 13:889–894

    Article  Google Scholar 

  12. Frugnoli I, Cappelli B, Chiesa R, Biral E, Noè A, Evangelio C et al (2010) Escalating doses of donor lymphocytes for incipient graft rejection following SCT for thalassemia. Bone Marrow Transpl 45:1047–1051

    Article  CAS  Google Scholar 

  13. Andreani M, Testi M, Battarra M, Indigeno P, Guagnano A, Polchi P et al (2008) Relationship between mixed chimerism and rejection after bone marrow transplantation in thalassaemia. Blood Transfus 6:143–149

    PubMed  PubMed Central  Google Scholar 

  14. Larocca A, Piaggio G, Podesta M, Pitto A, Bruno B, Di Grazia C et al (2006) Boost of CD34+ selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation. Haematologica 91:935–940

    PubMed  Google Scholar 

  15. Mainardi C, Ebinger M, Enkel S, Feuchtinger T, Teltschik HM, Eyrich M et al (2018) CD34+ selected stem cell boosts can improve poor graft function after paediatric allogeneic stem cell transplantation. Br J Haematol 180:90–99

    Article  CAS  Google Scholar 

  16. Klyuchnikov E, El-Cheikh J, Sputtek A, Lioznov M, Calmels B, Furst S et al (2014) CD34(+) selected stem cell boost without further conditioning for poor graft function after allogeneic stem cell transplantation in patients with hematological malignancies. Biol Blood Marrow Transpl 20:382–386

    Article  CAS  Google Scholar 

  17. Olsson R, Remberger M, Schaffer M, Berggren DM, Svahn BM, Mattsson J et al (2013) Graft failure in the modern era of allogeneic hematopoietic SCT. Bone Marrow Transpl 48:537–543

    Article  CAS  Google Scholar 

  18. Bukhari A, Dahiya S, Goloubeva O, Yip T, Rappaport A, Badros A et al (2019) Pattern of use and outcomes with donor lymphocyte infusion (DLI) and unmanipulated stem cell boost (SCB) after allogeneic hematopoietic stem cell transplant (HSCT): a single-center experience. Biol Blood Marrow Transpl 25(3):S250–S251

    Article  Google Scholar 

  19. Aker M, Kapelushnik J, Pugatsch T, Naparstek E, Ben-Neria S, Yehuda O et al (1998) Donor lymphocyte infusions to displace residual host hematopoietic cells after allogeneic bone marrow transplantation for beta-thalassemia major. J Pediatr Hematol Oncol 20:145–148

    Article  CAS  Google Scholar 

  20. Ho HK, Chiang AK, Kwong YL, Chan GC, Lau YL, Ha SY (2003) Pre-emptive treatment of early unstable mixed chimerism in Chinese thalassaemia major patient by graded peripheral blood stem cell infusions. Haematologica 88:ECR03

    PubMed  Google Scholar 

  21. Fouzia NA, Edison ES, Lakshmi KM, Korula A, Velayudhan SR, Balasubramanian P (2018) Longterm outcome of mixed chimerism after stem cell transplantation for thalassemia major conditioned with busulfan and cyclophosphamide. Bone Marrow Transpl 53(2):169–174

    Article  CAS  Google Scholar 

  22. Abraham A, Sindhuvi E, Korula A, Fouzia NA, Srivastava A, George B et al (2016) Donor lymphocyte infusion in patients with thalassemia major who have mixed chimerism following allogeneic stem cell transplant. Biol Blood Marrow Transpl 22:S138

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Akanksha Garg.

Ethics declarations

Conflict of interest

The authors have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garg, A., Shivchhand, A., Shah, S. et al. Unmanipulated Stem Cell Boost for Mixed Chimerism in Transfusion Dependent Thalassemia. Indian J Hematol Blood Transfus 37, 458–462 (2021). https://doi.org/10.1007/s12288-020-01347-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12288-020-01347-z

Keywords

Navigation