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Chapter 141 : Detecting Chimerism after Blood and Marrow Transplantation

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Abstract:

This chapter discusses fundamental aspects of laboratory assessment of hematopoietic chimerism after blood and marrow transplantation. Clinical indications for chimerism testing in blood and marrow transplantation include posttransplant monitoring of engraftment kinetics and stable mixed chimerism as well as detecting relapse and graft loss. Additional applications include detecting cells engrafted from a third party and distinguishing monozygotic and dizygotic twins. Chimerism testing is routinely used after allogeneic blood and marrow transplantation to monitor the status of the allograft and to detect relapse. In the early years of bone marrow transplantation, chimerism testing was primarily limited to use for monitoring donor engraftment. In 2005, the predominant methods for chimerism testing involve amplification of short tandem repeats (STR) loci. There are many situations in which there is coexistence of donor and host hematopoietic cells, and this phenomenon is referred to as mixed chimerism. In patients with mixed chimerism, the proportion (percentage) of donor cells can change, and this condition is described as increasing mixed chimerism if the percentage of donor cells is increasing or decreasing mixed chimerism if the percentage of donor cells is decreasing. For blood and marrow transplantation, chimerism analysis has become an important component of posttransplant monitoring. In addition to the clinical indications, chimerism testing can be used to test for the presence of third-party cells derived from blood transfusions, maternal cell engraftment in immunocompromised children, and maternal cell contamination of umbilical cord blood units.

Citation: Baxter-Lowe L. 2006. Detecting Chimerism after Blood and Marrow Transplantation, p 1269-1275. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch141

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Restriction Fragment Length Polymorphism
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Image of FIGURE 1
FIGURE 1

STR alleles. Two STR alleles that are distinguished by the numbers of tandem repeats of the sequence motif AAAG are depicted at the top of the figure. The solid black sections represent conserved sequences which are located in the flanking regions of the STR. Oligonucleotides labeled 5’ P and 3’ P anneal to these flanking regions to selectively prime DNA synthesis in the PCR. In this example, the 5’ P primer is labeled with a fluorescent dye molecule. The products of the PCR can be separated using slab gel electrophoresis (bottom left), and the fluorescence is often displayed as an electropherogram (bottom right).

Citation: Baxter-Lowe L. 2006. Detecting Chimerism after Blood and Marrow Transplantation, p 1269-1275. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch141
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Image of FIGURE 2
FIGURE 2

Electropherograms for a donor-recipient pair. Electropherograms for multiplex reactions for four loci are shown. For D21S11, the donor and recipient are homozygous for the same allele (223 bp). For D18S51, the recipient is homozygous for an allele with 285 bp. The donor shares this allele and has an additional informative allele (302 bp). For D16S539, the donor and recipient share the 364-bp allele, and there are informative alleles for the donor (360 bp) and recipient (352 bp). For Penta D, there are two informative recipient alleles (422 and 441 bp) and two informative donor alleles (397 and 417 bp).

Citation: Baxter-Lowe L. 2006. Detecting Chimerism after Blood and Marrow Transplantation, p 1269-1275. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch141
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Citation: Baxter-Lowe L. 2006. Detecting Chimerism after Blood and Marrow Transplantation, p 1269-1275. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch141
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Image of FIGURE 3
FIGURE 3

Admixtures of control DNA for a donor-recipient pair. The electropherogram for the homozygous recipient is shown in the top panel. The small peak to the immediate left of the main peak is a stutter peak. The panel labeled “100% Donor” shows the alleles from the control DNA from the donor. The small peak to the immediate left of the two large peaks is a stutter peak. Presumably, the stutter peak from the larger of the donor alleles comigrates with the smaller allele. The next panels show the amplification products of admixtures of donor and recipient DNA. Arrows show the host peak in the admixtures.

Citation: Baxter-Lowe L. 2006. Detecting Chimerism after Blood and Marrow Transplantation, p 1269-1275. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch141
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Image of FIGURE 4
FIGURE 4

Testing of cell subsets to increase sensitivity. The two upper left panels show the electropherograms of the host alleles and donor alleles. The host allele is undetectable in electrophero-grams for peripheral blood, CD14/15, and CD19 subsets using the standard scale and an expanded scale (right). For the CD3 subset, the host allele is barely detectable in the standard scale but is clearly evident in an expanded scale. Subset analysis not only provides increased sensitivity but also shows the lineage of the autologous cells.

Citation: Baxter-Lowe L. 2006. Detecting Chimerism after Blood and Marrow Transplantation, p 1269-1275. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch141
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References

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1. Alizadeh, M.,, M. Bernard,, B. Danic,, C. Dauriac,, B. Birebent,, C. Lapart,, T. Lamy,, P. Y. Le Prise,, A. Beauplet,, D. Bories,, G. Semana, and , E. Quelvennec. 2002. Quantitative assessment of hematopoietic chimerism after bone marrow transplantation by real-time quantitative polymerase chain reaction. Blood 99:46184625.
2. Antin, J. H.,, R. Childs,, A. H. Filipovich,, S. Giralt,, S. Mackinnon,, T. Spitzer, and , D. Weisdorf. 2001. Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem Meetings of the International Bone Marrow Transplant Registry and the American Society of Blood and Marrow Transplantation. Biol. Blood Marrow Transplant. 7:473485.
3. Bader, P.,, W. Holle,, T. Klingebiel,, R. Handgretinger,, N. Benda,, P. G. Schlegel,, D. Niethammer, and , J. Beck. 1997. Mixed hematopoietic chimerism after allogeneic bone marrow transplantation: the impact of quantitative PCR analysis for prediction of relapse and graft rejection in children. Bone Marrow Transplant. 19:697702.
4. Bader, P.,, W. Holle,, T. Klingebiel,, R. Handgretinger,, D. Niethammer, and , J. Beck. 1996. Quantitative assessment of mixed hematopoietic chimerism by polymerase chain reaction after allogeneic BMT Anticancer Res. 16:17591763.
5. Bader, P.,, H. Kreyenberg,, W. Hoelle,, G. Dueckers,, R. Handgretinger,, P. Lang,, B. Kremens,, D. Dilloo,, K. W. Sykora,, M. Schrappe,, C. Niemeyer,, A. Von Stackelberg,, B. Gruhn,, G. Henze,, J. Greil,, D. Niethammer,, K. Dietz,, J. F. Beck, and , T. Klingebiel. 2004. Increasing mixed chimerism is an important prognostic factor for unfavorable outcome in children with acute lymphoblastic leukemia after allogeneic stem-cell transplantation: possible role for pre-emptive immunotherapy? J. Clin. Oncol. 22:16961705.
6. Bader, P.,, H. Kreyenberg,, W. Hoelle,, G. Dueckers,, B. Kremens,, D. Dilloo,, K. W. Sykora,, C. Niemeyer,, D. Reinhardt,, J. Vormoor,, B. Gruhn,, P. Lang,, J. Greil,, R. Handgretinger,, D. Niethammer,, T. Klingebiel, and , J. E. Beck. 2004. Increasing mixed chimerism defines a high-risk group of childhood acute myelogenous leukemia patients after allogeneic stem cell transplantation where pre-emptive immunotherapy may be effective. Bone Marrow Transplant. 33:815821.
7. Bader, P.,, D. Niethammer,, A. Willasch,, H. Kreyenberg, and , T. Klingebiel. 2005. How and when should we monitor chimerism after allogeneic stem cell transplantation? Bone Marrow Transplant. 35:107119.
8. Bader, P.,, K. Stoll,, S. Huber,, A. Geiselhart,, R. Handgretinger,, C. Niemeyer,, H. Einsele,, P. G. Schlegel,, D. Niethammer,, J. Beck, and , T. Klingebiel. 2000. Characterization of lineage-specific chimerism in patients with acute leukemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse. Br. J. Haematol. 108:761768.
9. Baron, F.,, J. E. Baker,, R. Storb,, T. A. Gooley,, B. M. Sandmaier,, M. B. Maris,, D. G. Maloney,, S. Heimfeld,, D. Oparin,, E. Zellmer,, J. P. Radich,, F. C. Grumet,, K. G. Blume,, T. R. Chauncey, and , M. T. Little. 2004. Kinetics of engraftment in patients with hematologic malignancies given allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Blood 104:22542262.
10. Barrios, M.,, A. Jimenez-Velasco,, J. Roman-Gomez,, M. E. Madrigal,, J. A. Castillejo,, A. Torres, and , A. Heiniger. 2003. Chimerism status is a useful predictor of relapse after allogeneic stem cell transplantation for acute leukemia. Haematologica 88:801810.
11. Bianchi, D. W.,, G. K. Zickwolf,, G. J. Weil,, S. Sylvester, and , M. A. DeMaria. 1996. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc. Natl. Acad. Sci. USA 93:705708.
12. Blume, K. G.,, E. Beutler,, K. J. Bross,, G. M. Schmidt,, W. E. Spruce, and , R. L. Teplitz. 1980. Genetic markers in human bone marrow transplantation. Am. J. Hum. Genet. 32:414419.
13. Dewald, G. W.,, C. R. Schad,, E. R. Christensen,, M. E. Law,, A. R. Zinsmeister,, P. G. Stalboerger,, S. M. Jalal,, R. C. Ash, and , R. B. Jenkins. 1993. Fluorescence in situ hybridization with X and Y chromosome probes for cyto-genetic studies on bone marrow cells after opposite sex transplantation. Bone Marrow Transplant. 12:149154.
14. Drobyski, W.,, S. Thibodeau,, R. L. Truitt,, L. A. Baxter-Lowe,, J. Gorski,, R. Jenkins,, J. Gottschall, and , R. C. Ash. 1989. Third-party-mediated graft rejection and graft-versus-host disease after T-cell-depleted bone marrow transplantation, as demonstrated by hypervariable DNA probes and HLA-DR polymorphism. Blood 74:22852294.
15. Girgis, M.,, C. Hallemeier,, W. Blum,, R. Brown,, H. S. Lin,, H. Khoury,, L. T. Goodnough,, R. Vij,, S. Devine,, M. Wehde,, S. Postma,, A. Oza,, J. DiPersio, and , D. Adkins. 2004. Chimerism and clinical outcomes of 110 recipients of unrelated donor bone marrow transplants who underwent conditioning with low-dose, single-exposure total body irradiation and cyclophosphamide. Blood 105:30353041.
16. Guimond, M.,, L. Busque,, C. Baron,, Y. Bonny,, R. Belanger,, J. Mattioli,, C. Perreault, and , D. C. Roy. 2000. Relapse after bone marrow transplantation: evidence for distinct immunological mechanisms between adult and paediatric populations. Br. J. Haematol. 109:130137.
17. Hancock, J. P.,, N. J. Goulden,, A. Oakhill, and , C. G. Steward. 2003. Quantitative analysis of chimerism after allogeneic bone marrow transplantation using immunomagnetic selection and fluorescent microsatellite PCR. Leukemia 17:247251.
18. Hochberg, E. P.,, D. B. Miklos,, D. Neuberg,, D. A. Eichner,, S. F. McLaughlin,, A. Mattes-Ritz,, E. P. Alyea,, J. H. Antin,, R. J. Soiffer, and , J. Ritz. 2003. A novel rapid single nucleotide polymorphism (SNP)-based method for assessment of hematopoietic chimerism after allogeneic stem cell transplantation. Blood 101:363369.
19. Katz, F.,, S. Malcolm,, S. Strobel,, A. Finn,, G. Morgan, and , R. Levinsky. 1990. The use of locus-specific minisatellite probes to check engraftment following allogeneic bone marrow transplantation for severe combined immunodeficiency disease. Bone Marrow Transplant. 5:199204.
20. Khan, F.,, A. Agarwal, and , S. Agrawal. 2004. Significance of chimerism in hematopoietic stem cell transplantation: new variations on an old theme. Bone Marrow Transplant. 34:112.
21. Kreyenberg, H.,, W. Holle,, S. Mohrle,, D. Niethammer, and , P. Bader. 2003. Quantitative analysis of chimerism after allogeneic stem cell transplantation by PCR amplification of microsatellite markers and capillary electrophoresis with fluorescence detection: the Tuebingen experience. Leukemia 17:237240.
22. Lee, T. H.,, T. Paglieroni,, H. Ohto,, P. V. Holland, and , M. P. Busch. 1999. Survival of donor leukocyte subpopula-tions in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients. Blood 93:31273139.
23. Maas, F.,, N. Schaap,, S. Kolen,, A. Zoetbrood,, I. Buno,, H. Dolstra,, T. de Witte,, A. Schattenberg, and , E. van de Wiel-van Kemenade. 2003. Quantification of donor and recipient hemopoietic cells by real-time PCR of single nucleotide polymorphisms. Leukemia 17:621629.
24. Matsuda, K.,, K. Yamauchi,, M. Tozuka,, T. Suzuki,, M. Sugano,, E. Hidaka,, K. Sano, and , T. Katsuyama. 2004. Monitoring of hematopoietic chimerism by short tandem repeats, and the effect of CD selection on its sensitivity. Clin. Chem. 50:24112414.
25. Nollet, F.,, J. Billiet,, D. Selleslag, and , A. Criel. 2001. Standardization of multiplex fluorescent short tandem repeat analysis for chimerism testing. Bone Marrow Transplant. 28:511518.
26. Poli, F.,, S. M. Sirchia,, M. Scalamogna,, I. Garagiola,, L. Crespiatico,, L. Pedranzini,, L. Lecchi, and , G. Sirchia. 1997. Detection of maternal DNA in human cord blood stored for allotransplantation by a highly sensitive chemilu-minescent method. J. Hematother. 6:581585.
27. Scharf, S. J.,, A. G. Smith,, J. A. Hansen,, C. McFarland, and , H. A. Erlich. 1995. Quantitative determination of bone marrow transplant engraftment using fluorescent poly-merase chain reaction primers for human identity markers. Blood 85:19541963.
28. Scheffold, C.,, M. Kroeger,, M. Zuehlsdorf,, J. Tchinda,, G. Silling,, G. Bisping,, M. Stelljes,, T. Buechner,, W. E. Berdel, and , J. Kienast. 2004. Prediction of relapse of acute myeloid leukemia in allogeneic transplant recipients by marrow CD34+ donor cell chimerism analysis. Leukemia 18:20482050.
29. Schraml, E., and , T. Lion. 2003. Interference of dye-associated fluorescence signals with quantitative analysis of chimerism by capillary electrophoresis. Leukemia 17:221223.
30. Shimoni, A.,, A. Nagler,, C. Kaplinsky,, M. Reichart,, A. Avigdor,, I. Hardan,, M. Yeshurun,, M. Daniely,, Y. Zilberstein,, N. Amariglio,, F. Brok-Simoni,, G. Rechavi, and , L. Trakhtenbrot. 2002. Chimerism testing and detection of minimal residual disease after allogeneic hematopoietic transplantation using the bioView (Duet) combined morphological and cytogenetical analysis. Leukemia 16: 1413-1418, 1419-1422.
31. Starzl, T. E.,, A. J. Demetris,, M. Trucco,, H. Ramos,, A. Zeevi,, W. A. Rudert,, M. Kocova,, C. Ricordi,, S. Ildstad, and , N. Murase. 1992. Systemic chimerism in human female recipients of male livers. Lancet 340:876877.
32. Suttorp, M.,, N. Schmitz,, P. Dreger,, J. Schaub, and , H. Loftier. 1993. Monitoring of chimerism after allogeneic bone marrow transplantation with unmanipulated marrow by use of DNA polymorphisms. Leukemia 7:679687.
33. Thiede, C.,, M. Bornhauser, and , G. Ehninger. 2004. Evaluation of STR informativity for chimerism testing— comparative analysis of 27 STR systems in 203 matched related donor recipient pairs. Leukemia 18:248254.
34. Thiede, C.,, K. Lutterbeck,, U. Oelschlagel,, M. Kiehl,, C. Steudel,, U. Platzbecker,, C. Brendel,, A. A. Fauser,, A. Neubauer,, G. Ehninger, and , M. Bornhauser. 2002. Detection of relapse by sequential monitoring of chimerism in circulating CD34+ cells. Ann. Hematol. 81:S27S28.
35. Walsh, P. S.,, N. J. Fildes, and , R. Reynolds. 1996. Sequence analysis and characterization of stutter products at the tetranucleotide repeat locus vWA. Nucleic Acids Res. 24:28072812.

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