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.

  • Letter to the Editor
  • Published:

Correlation between paraproteinaemia and viral reactivation after allo-SCT

Bone Marrow Transplantation volume 47, page 1262 (2012)Cite this article

Subjects

Medd et al.,1 retrospectively studied the occurrence of paraproteinaemia after allo-SCT in a cohort of 91 patients. They detected a paraproteinaemia incidence of 32%, multiple in the majority of cases, with a predominance of an IgG isotype and with equal kappa/lambda restriction. In this report, the most important risk factor for the development of post-transplant paraproteinaemia was CMV reactivation, which was more frequent when alemtuzumab was included in conditioning regimen. The authors also described a poorer OS in patients with paraproteinaemia, with relapse being the commonest cause of death in this group of patients. None of the patients with paraproteinaemia subsequently developed myeloma or a lymphoproliferative disorder and only one patient developed cryoglobulinemia. In this study, EBV reactivation was not monitored. Babel et al.2 first reported the association between the occurrence of paraproteinaemia and EBV reactivation after renal transplantation. Since then, paraproteinaemia has been largely reported in solid organ transplant recipients reactivating EBV.3, 4, 5, 6 More recently, we reported the association between EBV reactivation after SCT and the occurrence of abnormalities in γ-region at serum protein electrophoresis (SPE) in a cohort of 79 patients.7 EBV reactivation was detected in 49/79 patients (62%), 43 of them show asymptomatic EBV-DNAemia, whereas the other 6 patients progressed to EBV-related post-transplant lymphoproliferative disease. The global incidence of abnormalities in γ-region at SPE after allo-SCT in patients with EBV reactivation was 65.3% (32/49 patients), whereas it was 37.5% (9/24 evaluable) in patients who did not present viral reactivation (P=0.02). Paraproteinaemia after HSCT was identified in 23/28 evaluable patients (82%) with EBV reactivation and in 4/7 evaluable patients (57%) without viral reactivation, with a median level of 1.8 g/dL (range 0.07–3.5 g/dL). CMV reactivation was co-present in 17/49 patients, 13 of them with abnormalities in γ-region at SPE and 9/13 with also a paraproteinaemia. Considering that alemtuzumab, adopted by Medd et al.1 as GVHD prophylaxis in the series of patients with paraproteinemia, is considered as a risk factor for EBV reactivation after allogenic SCT, the role of CMV reactivation per se as a risk factor for the subsequent development of paraproteinemia should be kept with caution in the absence of EBV viral load monitoring.8, 9 In our series, pre-emptive therapy for EBV reactivation was able to modify the extent of paraproteinemia leading to complete disappearance of gammopathy in a significant number of patients and it calls for a causative effect. We propose that EBV reactivation evaluation should be carried out in patients submitted to allogeneic SCT as recommended by European Conference of Infections in Leukemia,10 particularly when recognized risk factors are present. Medd et al.1 did not perform an EBV load monitoring in patients after HSCT, and they reported that there is no evidence of progression to lymphoproliferative disorder in patients with paraproteinaemia after HSCT. In our cohort, 5/6 patients with post-transplant lymphoproliferative disease showed a paraproteinaemia and in 2 cases it persisted also after EBV clearance after Rituximab therapy. In contrast to that reported by Medd et al., in our experience no significant difference in OS of patients with EBV reactivation was seen between patients with or without paraproteinaemia.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

References

  1. Medd P, Littlewood S, Danby R, Malladi R, Clifford R, Wareham D et al. Paraproteinaemia after allo-SCT, association with alemtuzumab-based conditioning and CMV reactivation. Bone Marrow Transplant 2011; 46: 993–999.

    Article  CAS  PubMed  Google Scholar 

  2. Babel N, Schwarzmann F, Pruss A, Volk HD, Reinke P . Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased frequency of Epstein-Barr Virus (EBV) latently infected B lymphocytes in long-term renal transplant patients. Transplant Proc 2004; 36: 2679–2682.

    Article  CAS  PubMed  Google Scholar 

  3. Badley AD, Portela DF, Patel R, Kyle RA, Habermann TM, Strickler JG et al. Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder. Liver Transpl Surg 1996; 2: 375–382.

    Article  CAS  PubMed  Google Scholar 

  4. Lemoine A, Pham P, Azoulay D, Saliba F, Emile JF, Saffroy R et al. Detection of gammopathy by serum protein electrophoresis for predicting and managing therapy of lymphoproliferative disorder in 911 recipients of liver transplants. Blood 2001; 98: 1332–1338.

    Article  CAS  PubMed  Google Scholar 

  5. Tsai DE, Aqui NA, Tomaszewski JE, Olthoff KM, Ahya VN, Kotloff RM et al. Serum protein electrophoresis abnormalities in adult solid organ transplant patients with post-transplant lymphoproliferative disorder. Clin Transplant 2005; 19: 644–652.

    Article  PubMed  Google Scholar 

  6. Rosselet A, Vu DH, Meylan P, Baur Chaubert AS, Schapira M, Pascual M et al. Association of serum EBV DNA and gammopathy with post-transplant lymphoproliferative disease. Clin Transplant 2009; 23: 74–82.

    Article  PubMed  Google Scholar 

  7. Chiusolo P, Metafuni E, Cattani P, Piccirillo N, Santangelo R, Manzara S et al. Prospective evaluation of epstein-barr virus reactivation after stem cell transplantation: association with monoclonal gammopathy. J Clin Immunol 2010; 30: 894–902.

    Article  PubMed  Google Scholar 

  8. Lim ZY, Ingram W, Brand R, Akthari M, Milojkovic D, Ho AY et al. Clonal gammopathies following alemtuzumab-based reduced intensity conditioning haematopoietic stem cell transplantation: association with chronic graft-versus-host disease and improved overall survival. Bone Marrow Transplant 2007; 40: 747–752.

    Article  CAS  PubMed  Google Scholar 

  9. Sorà F, Laurenti L, Chiusolo P, De Matteis S, Leone G, Sica S . Clonal gammopathies and allogeneic stem cell transplantation. Bone Marrow Transplant 2008; 41: 317.

    Article  PubMed  Google Scholar 

  10. Styczynski J, Reusser P, Einsele H, de la Camara R, Cordonnier C, Ward KN et al. Management of HSV. VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on infectious in Leukemia. Bone Marrow Transplant 2009; 43: 757–770.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Hematology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy

    E Metafuni, S Giammarco, S Bellesi, P Chiusolo, L Laurenti, F Sorà, G Leone & S Sica

  2. Institute of Microbiology, Policlinico A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy

    P Cattani, R Santangelo & S Manzara

Authors
  1. E Metafuni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Giammarco
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Bellesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Chiusolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L Laurenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F Sorà
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P Cattani
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R Santangelo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S Manzara
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G Leone
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S Sica
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Sica.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Metafuni, E., Giammarco, S., Bellesi, S. et al. Correlation between paraproteinaemia and viral reactivation after allo-SCT. Bone Marrow Transplant 47, 1262 (2012). https://doi.org/10.1038/bmt.2012.11

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2012.11

This article is cited by

Search

Advanced search

Quick links