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.

Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation

Abstract

Central nervous system (CNS) complications have been described in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). Cerebrospinal fluid (CSF) analysis is included in the diagnostic workup in patients with neurological symptoms after alloHCT. CSF donor–recipient chimerism analysis usually is not used to evaluate patients with neurological complications after alloHCT. To assess the potential contribution of CSF donor–recipient chimerism in patients with neurological complications, we analyzed 85 CSF samples from 50 patients with neurological complications after alloHCT. After alloHCT, 21 patients showed the presence of recipient-derived DNA. In 13 of these patients, recurrence of the underlying disease was detected in CSF. There was a moderate correlation between the recipient DNA percentage as detected by short tandem repeat (STR) amplification and the cell concentration in CSF (Spearmann r: 0.66 P=0.004). The percentage of cells with immunophenotypic abnormalities from patients relapsing in the CNS detected by flow cytometry showed a strong correlation with the percentage of recipient-derived DNA in CSF assessed by STR analysis (Spearmann r: 0.83 P=0.0008). Donor–recipient chimerism analysis in CSF in patients with neurological symptoms after alloHCT is a practical, feasible and useful complementary method to the already established methodologies included in the diagnostic workup.

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

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 2

References

  1. Siegal D, Keller A, Xu W, Bhuta S, Kim DH, Kuruvilla J et al. Central nervous system complications after allogeneic hematopoietic stem cell transplantation: incidence, manifestations and clinical significance. Biol Blood Marrow Transplant 2007; 13: 1369–1379.

    Article  Google Scholar 

  2. Hamdi A, Mawad R, Bassett R, di Stasi A, Ferro R, Afrough A et al. Central nervous system relapse in adults with acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2014; 20: 1767–1771.

    Article  Google Scholar 

  3. Glantz MJ, Cole BF, Glantz LK, Cobb J, Mills P, Lekos A et al. Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer 1998; 82: 733–739.

    Article  CAS  Google Scholar 

  4. Bromberg JE, Breems DA, Kraan J, Bikker G, van der Holt B, Smitt PS et al. CSF flow cytometry greatly improves diagnostic accuracy in CNS hematologic malignancies. Neurology 2007; 68: 1674–1679.

    Article  CAS  Google Scholar 

  5. Liu L, Cao F, Wang S, Zhou J, Yang G, Wang C . Detection of malignant B lymphocytes by PCR clonality assay using direct lysis of cerebrospinal fluid and low volume specimens. Int J Lab Hematol 2014; 37: 165–173.

    Article  Google Scholar 

  6. Baehring JM, Hochberg FH, Betensky RA, Longtine J, Sklar J . Immunoglobulin gene rearrangement analysis in cerebrospinal fluid of patients with lymphoproliferative processes. J Neurol Sci 2006; 247: 208–216.

    Article  CAS  Google Scholar 

  7. Hibi S, Tsunamoto K, Todo S, Sawada T, Ueda Y, Taniwaki M et al. Chimerism analysis on mononuclear cells in the CSF after allogeneic bone marrow transplantation. Bone Marrow Transplant 1997; 20: 503–506.

    Article  CAS  Google Scholar 

  8. Ohashi H, Kato C, Fukami S, Saito H, Hamaguchi M . Leukemic relapse in the central nervous system after allogeneic stem cell transplantation with complete remission in the bone marrow and donor-type chimerism: report of two cases. Am J Hematol 2005; 79: 142–146.

    Article  Google Scholar 

  9. Subira D, Castañon S, Roman A, Aceituno E, Jimenez-Garofano C, Jimenez A et al. Flow cytometry and the study of central nervous disease in patients with acute leucemia. Br J Haematol 2001; 112: 381–384.

    Article  CAS  Google Scholar 

  10. Roma AA, Garcia A, Avagnina A, Rescia C, Elsner B . Lymphoid and myeloid neoplasm involving cerebrospinal fluid: comparison of morphologic examination and immunophenotyping by flow cytometry. Diagn Cytopathol 2002; 27: 271–275.

    Article  Google Scholar 

  11. Marks R, Potthoff K, Hahn J, Ihorst G, Bertz H, Spyridonidis A et al. Reduced-toxicity conditioning with fludarabine, BCNU and melphalan in allogeneic cell transplantation: particular activity against advanced hematologic malignancies. Blood 2008; 112: 415–425.

    Article  CAS  Google Scholar 

  12. Spyridonidis A, Zeiser R, Wäsch R, Bertz H, Finke J . Capillary electrophoresis for chimerism monitoring by PCR amplification of microsatellite markers after allogeneic hematopoietic cell transplantation. Clin Transplant 2005; 19: 350–356.

    Article  Google Scholar 

  13. Kristt D, Klein T . Reliability of quantitative chimerism results: assessment of sample performance using novel parameters. Leukemia 2006; 20: 1169–1172.

    Article  CAS  Google Scholar 

  14. Oelschlägel U, Nowak R, Schaub A, Köppel C, Herbst R, Mohr B et al. Shift of aberrant antigen expression at relapse or at treatment failure in acute leukemia. Cytometry 2000; 42: 247–253.

    Article  Google Scholar 

  15. Crespo-Solis E, Lopez-Karpovitch X, Higuera J, Vega-Ramos B . Diagnosis of acute leukemia in cerebrospinal fluid. Curr Oncol Rep 2012; 14: 369–378.

    Article  Google Scholar 

  16. de Graaf MT, de Jongste AH, Kraan J, Boostra JG, Sillevis Smitt PA, Gratama JW . Flow cytometric characterization of cerebrospinal fluid cells. Cytometry B Clin Cytom 2011; 80: 271–281.

    Article  Google Scholar 

  17. Dissing M, Le Beau MM, Pedersen-Bjergaard J . Inversion of chromosome 16 and uncommon rearrangements of the CBFB and MYH11 genes in therapy-related acute myeloid leukemia: rare events related to DNA-topoisomerase II inhibitors? J Clin Oncol 1998; 16: 1890–1896.

    Article  CAS  Google Scholar 

  18. Waterhouse M, Kunzmann R, Torres M, Bertz H, Finke J . An internal validation approach and quality control on hematopoieitc chimerism testing after allogeneic hematopoietic cell transplantation. Clin Chem Lab Med 2013; 51: 363–369.

    Article  CAS  Google Scholar 

  19. van den Berg H, Gerritsen EJ, Haraldsson A, Vossen JM . Changes in cell and protein content of cerebrospinal fluid in children with acute lymphoblastic leukaemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1993; 12: 615–619.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to the transplantation team at Freiburg University Hospital.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Waterhouse.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Waterhouse, M., Bartsch, I., Bertz, H. et al. Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation. Bone Marrow Transplant 51, 127–131 (2016). https://doi.org/10.1038/bmt.2015.226

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2015.226

Search

Quick links