Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Allografting

Chimerism monitoring following allogeneic hematopoietic stem cell transplantation

Abstract

Information regarding the chimeric status of hematopoietic stem cell transplantation (HSCT) recipients is of great significance when comparing different conditioning and prophylactic therapies. In recent years, short tandem repeats/variable number tandem repeats (STRs/VNTRs) have emerged as the best tool for chimerism monitoring. However, the polymorphisms of STR/VNTR markers vary within and between ethnic groups. The issue is further complicated in a heterogeneous population such as occurs in the Indian subcontinent. In the present study, we attempted to devise a robust scheme to identify a set of polymorphic STRs/VNTRs most suitable for chimerism evaluation in north Indian HCST recipients. At first, we did genotyping of 11 STR and one VNTR in 1000 randomly chosen north Indian individuals to quantify different diversity parameters. Resulting data indicated that ApoB3′HVR, FES, VWA, D3S1358 and D16S310 were most polymorphic loci with the average heterozygosity being 0.756±0.17. Furthermore, all markers were genotyped in 77 HLA-matched donor–recipient pairs to evaluate the informativeness in differentiating donor's and recipient's cells. A panel of seven markers (ApoB3HVR-D3S1358-HUM-THO1-VWF-1-D16S310-FES-VWA) differentiated 98.70% of donor–recipient pairs. This set of markers also successfully monitored the graft status in 14 HSCT cases during multiple time points following HSCT. The results were compared to the commercially available AmpF/STR SGM Plus multiplex PCR kit (Applied Biosystems, Foster City, CA, USA). Our findings established that the panel of seven markers we identified was more cost-effective and informative.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Cavalli-Sforza LL, Feldman MW . The application of molecular genetic approaches to the study of human evolution. Nat Genet 2003; 33 (Suppl): 266–275.

    Article  CAS  Google Scholar 

  2. Fischer A, Wiebe V, Paabo S, Przeworski M . Evidence for a complex demographic history of chimpanzees. Mol Biol Evol 2004; 21: 799–808.

    Article  CAS  Google Scholar 

  3. Jorde LB, Wooding SP . Genetic variation, classification and ‘race’. Nat Genet 2004; 36: S28–S33.

    Article  CAS  Google Scholar 

  4. Khan F, Phadke S, Nityanand S, Talwar S, Agrawal S . Use of ApoB′ hyper variable region in studying mixed chimerism and maternal contamination in North Indian populations. J Clin Forensic Med 2004; 11: 183–188.

    Article  Google Scholar 

  5. Slavin S, Nagler A, Kapelushnik Y, Aker M, Cividalli G, Varadi G et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  6. Khan F, Agarwal A, Agrawal S . Significance of chimerism in hematopoietic stem cell transplantation: new variations on an old theme. Bone Marrow Transplant 2004; 34: 1–12.

    Article  CAS  Google Scholar 

  7. Schaap N, Schattenberg A, Bar B, Mensink E, de Man A, Geurts van Kessel A et al. Red blood cell phenotyping is a sensitive technique for monitoring chronic myeloid leukaemia patients after T-cell-depleted bone marrow transplantation and after donor leucocyte infusion. Br J Haematol 2000; 108: 116–125.

    Article  CAS  Google Scholar 

  8. Roy DC, Tantravahi R, Murray C, Dear K, Gorgone B, Anderson KC et al. Natural history of mixed chimerism after bone marrow transplantation with CD6-depleted allogeneic marrow: a stable equilibrium. Blood 1990; 75: 296–304.

    CAS  PubMed  Google Scholar 

  9. Seong CM, Giralt S, Kantarjian H, Xu J, Swantkowski J, Hayes K et al. Early detection of relapse by hypermetaphase fluorescence in situ hybridization after allogeneic bone marrow transplantation for chronic myeloid leukemia. J Clin Oncol 2000; 18: 1831–1836.

    Article  CAS  Google Scholar 

  10. Alizadeh M, Bernard M, Danic B, Dauriac C, Birebent B, Lapart C et al. Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood 2002; 99: 4618–4625.

    Article  CAS  Google Scholar 

  11. Sellathamby S, Balasubramanian P, Sivalingam S, Shaji RV, Mathews V, George B et al. Developing an algorithm of informative markers for evaluation of chimerism after allogeneic bone marrow transplantation. Bone Marrow Transplant 2006; 37: 751–755.

    Article  CAS  Google Scholar 

  12. Coomey CT, Koons BW, Presley KW, Smerick JB, Sobieralski CA, Stanley DM . DNA extraction strategies for amplified fragment length polymorphism analysis. J Forensic Sci 1994; 39: 1254–1269.

    Article  Google Scholar 

  13. Perez-lezaun A, Calafell F, Mateu E, Comas D, Bosch E, Bertranpetit J . Allele frequency for 20 microsatellites in a worldwide population survey. Hum Hered 1997; 47: 189–196.

    Article  CAS  Google Scholar 

  14. Childs R, Clave E, Contentin N, Jayasekera D, Hensel N, Leitman S et al. Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses. Blood 1999; 94: 3234–3241.

    CAS  PubMed  Google Scholar 

  15. Frossard PM, Lestringant GG . Analysis of an apolipoprotein B gene 3′ hypervariable region among Abhu Dhabi emirates. Ann Saudi Med 2001; 19: 490–494.

    Article  Google Scholar 

  16. Rosenberg NA, Pritchard JK, Weber JL, Cann HM, Kidd KK, Zhivotovsky LA et al. Genetic structure of human populations. Science 2002; 298: 2381–2385.

    Article  CAS  Google Scholar 

  17. Agrawal S, Muller B, Bharadwaj U, Bhatnagar S, Sharma A, Khan F et al. Microsatellite variation at 24 STR loci in three endogamous groups of Uttar Pradesh, India. Hum Biol 2003; 75: 97–104.

    Article  Google Scholar 

  18. Das B, Chauhan PS, Sheshadri MS . Genetic polymorphism study at four minisatellite loci (D1S80, D17S5, D19S20 and APOB) among five Indian population groups. Hum Biol 2002; 74: 345–361.

    Article  Google Scholar 

  19. Thiede C, Bornhauser M, Ehninger G . Evaluation of STR informativity for chimerism testing--comparative analysis of 27 STR systems in 203 matched related donor–recipient pairs. Leukemia 2004; 18: 248–254.

    Article  CAS  Google Scholar 

  20. Hassan R, Bonamino MH, Braggio E, Lobo AM, Seuanez HN, Tabak DG et al. A systematic approach to molecular quantitative determination of mixed chimerism following allogeneic bone marrow transplantation: an analysis of its applicability in a group of patients with severe aplastic anaemia. Eur J Haematol 2004; 73: 156–161.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Indian Council of Medical Research (ICMR) New Delhi and the Sanjay Gandhi Post Graduate Institute of Medical Sciences Lucknow for providing various lab facilities and for other assistance. We appreciate the assistance of Dr Catherine Ivory in carrying out the linguistic modifications of the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S Agrawal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Talwar, S., Khan, F., Nityanand, S. et al. Chimerism monitoring following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 39, 529–535 (2007). https://doi.org/10.1038/sj.bmt.1705626

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705626

Keywords

This article is cited by

Search

Quick links