Skip to main content
SpringerLink
Log in

Posttransplant Lymphoproliferative Disease (PTLD) in Hematopoietic Stem Cell Transplantation (HSCT)

  • Chapter
Book cover Post-Transplant Lymphoproliferative Disorders

Core Messages

  • Posttransplant lymphoproliferative disorders (PTLD) following hematopoietic stem cell transplantation (HSCT) is nearly 100% associated with EBV and occurs 3–6 months posttransplant.

  • T cell depletion (TCD) of the hematopoietic stem cell graft (ex vivo or in vivo) is the strongest risk factor for developing PTLD. Anything that stimulates B cell proliferation and/or delays EBV cytotoxic T cell (EBV-CTL) recovery will increase the risk for PTLD.

  • Comparisons of results in the literature for incidence of PTLD and outcomes of therapies are difficult due to differing definitions, i.e., EBV infection vs. EBV disease vs. PTLD.

  • Preemptive therapy with rituximab for high-risk patients has reduced incidence and mortality of PTLD following HSCT.

  • Adoptive EBV-specific cytotoxic T cell therapy is the most effective therapy in the prevention and treatment of PTLD post-HSCT, but it is not widely available.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Barker JN, Martin PL, Coad JE, et al. Low incidence of Epstein-Barr virus-associated posttransplantation lymphoproliferative disorders in 272 unrelated-donor umbilical cord blood transplant recipients. Biol Blood Marrow Transplant. 2001;7:395–9

    Article  PubMed  CAS  Google Scholar 

  2. Benkerrou M, Jais J-P, Leblond V, et al. Anti-B-cell monoclonal antibody treatment of severe post-transplant B-lymphocyte disorder: prognostic factors and long-term outcome. Blood. 1998; 92:3137–47

    PubMed  CAS  Google Scholar 

  3. Bhatia S, Ramsay NKC, Steinbuch M, et al. Malignant neoplasms following bone marrow transplantation. Blood. 1996;87:3633–9

    PubMed  CAS  Google Scholar 

  4. Bonini C, Ferrari G, Verzeletti S, et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science. 1997;276:1719–24

    Article  PubMed  CAS  Google Scholar 

  5. Brunstein CG, Weisdorf DJ, Defor T, et al. Marked increased risk of Epstein-Barr virus-related complications with the addition of anti-thymocyte globulin to a non-myeloablative conditioning prior to unrelated umbilical cord blood transplantation. Blood. 2006;108:2874–89

    Article  PubMed  CAS  Google Scholar 

  6. Buell JF, Gross TG, Woodle ES. Malignancy after transplantation. Transplantation. 2005;80: S254–64

    Article  PubMed  Google Scholar 

  7. Cohen J, Gandhi M, Naik P, et al. Increased incidence of EBV-related disease following paediat-ric stem cell transplantation with reduced-intensity conditioning. Br J Haemtaol. 2005;129: 229–39

    Article  Google Scholar 

  8. Cohen JM, Cooper N, Chakrabarti S, et al. EBV-related disease following hematopoietic stem cell transplantation with reduced intensity conditioning. Leuk Lymph. 2007;48:256–69

    Article  Google Scholar 

  9. Comoli P, Basso S, Zecca M, et al. Preemptive therapy of EBV-related lymphoproliferative disease after pediatric haploidentical stem cell transplantation. Am J Transplant. 2007;7:1648–55

    Article  PubMed  CAS  Google Scholar 

  10. Curtis RE, Travis LB, Rowlings PA, et al. Risk of lymphoproliferative disorders after bone marrow transplantation: a multi-institutional study. Blood. 1999;94:2208–16

    PubMed  CAS  Google Scholar 

  11. Gratama JW, Oosterveer MA, Zwaan FE, et al. Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implication for sites of viral latency. Proc Natl Acad Sci USA. 1988;85:8693–6

    Article  PubMed  CAS  Google Scholar 

  12. Gross TG, Hinrichs SH, Davis JR, et al. Effect of counterflow elutriation (CE) on Epstein-Barr virus (EBV) infected cells in donor bone marrow. Exp Hematol. 1998;26:395–9

    PubMed  CAS  Google Scholar 

  13. Gross TG, Steinbuch M, DeFor T, et al. B cell lymphoproliferative disorder following hematopoietic stem cell transplantation: Risk factors, treatment and outcome. Bone Marrow Transplant. 1999;23:251–8

    Article  PubMed  CAS  Google Scholar 

  14. Gross TG, Bucuvalas J, Park J, et al. Low dose chemotherapy for the treatment of refractory post-transplant lymphoproliferative disease in children. J Clin Oncol. 2005;23:6481–8

    Article  PubMed  CAS  Google Scholar 

  15. Gustafsson A, Levitsky V, Zou JZ, et al. Epstein-Barr virus (EBV) load in bone marrow transplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells. Blood. 2000;95:807–14

    PubMed  CAS  Google Scholar 

  16. Harris NL, Ferry JA, Swerdlow SH. Posttransplant lymphoproliferative disorders: summary of Society for Hematopathology Workshop. Semin Diagn Pathol. 1997;14:8–14

    PubMed  CAS  Google Scholar 

  17. Ho M, Jaffe R, Miller G, et al. The frequency of Epstein-Barr virus infection and associated lym-phoproliferative syndrome after transplantation and its manifestations in children. Transplantation. 1998;45:719–27

    Article  Google Scholar 

  18. Kuehnle I, Huls MH, Liu Z, et al. CD20 monoclonal antibody (rituximab) for therapy of Epstein-Barr virus lymphoma after hemopoietic stem-cell transplantation. Blood. 2000;95:1502–5

    PubMed  CAS  Google Scholar 

  19. Kuzushima K, Hoshino Y, Fujii K, et al. Rapid determination of Epstein-Barr virus-specific CD8+ T-cell frequencies by flow cytometry. Blood. 1999;94:3094–100

    PubMed  CAS  Google Scholar 

  20. Lucas KG, Burton RL, Zimmerman SE, et al. Semiquantitative Epstein-Barr virus (EBV) poly-merase chain reaction for determination of patients at risk for EBV-induced lymphoprolifera-tive disease after stem cell transplantation. Blood. 1998;91:3654–61

    PubMed  CAS  Google Scholar 

  21. Marshall NA, Howe JG, Formica R, et al. Rapid reconstitution of Epstein-Barr virus-specific T lymphocytes following allogeneic stem cell transplantation. Blood. 2000;96:2814–21

    PubMed  CAS  Google Scholar 

  22. Meij P, van Esser JWJ, niesters HGM, et al. Impaired recovery of Epstein-Barr virus (EBV)-specific CD8+ T lymphocytes after partially T-depleted allogeneic stem cell transplantation may identify patients at very high risk for progressive EBV reactivation and lymphoproliferative disease. Blood. 2003;101:4290–7

    Article  PubMed  CAS  Google Scholar 

  23. Milpied N, Vasseur B, Parquet N, et al. Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: a retrospective analysis on 32 patients. Ann Oncol. 2000;11:113–6

    Article  PubMed  Google Scholar 

  24. Ocheni S, Kroeger N, Zabelina T, et al. EBV reactivation and post transplant lymphoprolifera-tive disorders following allogeneic SCT. Bone Marrow Transplant. 2008;42:181–6

    Article  PubMed  CAS  Google Scholar 

  25. Papadopoulos EB, Ladanyi M, Emanuel D, et al. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N Engl J Med. 1994;330:1185–91

    Article  PubMed  CAS  Google Scholar 

  26. Perrine SP, Hermine O, Small T, et al. A phase » trial of arginine butyrate and ganciclovir on patients with Epstein-Barr virus-associated lymphoid malignancies. Blood. 2007;109:2571–8

    Article  PubMed  CAS  Google Scholar 

  27. Rooney CM, Smith CA, Ng CYC, et al. Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood. 1998;92:1549–55

    PubMed  CAS  Google Scholar 

  28. Rowe DT, Webber S, Shcauer EM, et al. Epstein-Barr virus load monitoring: its role in the prevention and management of post-transplant lymphoproliferative disease. Transplant Infect Dis. 2001;3:79–87

    Article  CAS  Google Scholar 

  29. Shapiro R, Nalesnik M, McCauley J, et al. Posttransplant lymphoproliferative disorders in adult and pediatric renal transplant patients receiving tacrolimus-based immunosuppression. Transplantation. 1999;68:1851–4

    Article  PubMed  CAS  Google Scholar 

  30. Swinnen LJ, Mullen GM, Carr TJ, Costanzo MR, Fisher RI. Aggressive treatment for postcar-diac lymphoproliferation. Blood. 1995;86:3333–40

    PubMed  CAS  Google Scholar 

  31. Tan LC, Gudgeon N, Annels NE, et al. A re-evaluation of the frequency of CD8+ T cells spe-cific for EBV in healthy carriers. J Immunol. 1999;162:1827–35

    PubMed  CAS  Google Scholar 

  32. Tiberghien P, Ferrand C, Lioure B, et al. Administration of herpes simplex-thymidine kinase-expressing donor T-cells with a T-cell-depleted allogeneic marrow graft. Blood. 2001;97:63–72

    Article  PubMed  CAS  Google Scholar 

  33. van Esser JWJ, van der Holt B, Meijer E, et al. Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation (SCT) and quantitatively predicts EBV-lymphoproliferative disease following T-cell-depleted SCT. Blood. 2001;98:972–8

    Article  PubMed  Google Scholar 

  34. van Esser JWJ, Niesters HGM, van der Holt B, et al. Prevention of Epstein-Barr virus-lym-phoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation. Blood. 2002;99:4364–9

    Article  PubMed  Google Scholar 

  35. Witherspoon RP, Fisher LD, Schoch G, et al. Secondary cancers after bone marrow transplantation for leukemia or aplastic anemia. N Engl J Med. 1989;321:784–9

    Article  PubMed  CAS  Google Scholar 

  36. Yang J, Lemas VM, Flinn IW, et al. Application of the ELISPOT assay to the characterization of CD8 + responses to Epstein-Barr virus antigens. Blood. 2000;95:241–8

    PubMed  CAS  Google Scholar 

  37. Yang J, Tao Q, Flinn IW, et al. Characterization of Epstein-Barr virus-infected B cells in patients with posttransplantation lymphoproliferative disease: disappearance after rituximab therapy does not predict clinical response. Blood. 2000;96:4055–63

    PubMed  CAS  Google Scholar 

  38. Zutter MM, Martin PJ, Sale GE, et al. Epstein-Barr virus lymphoproliferation after bone marrow transplantation. Blood. 1998;72:520–9

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology/BMT, Nationwide Children' Hospital, Columbus, OH, 43205, USA

    Thomas G. Gross

Authors
  1. Thomas G. Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Pediatric Kidney Transplantation, Shands Hospital at UF, University of Florida College of Medicine Medical Director, Gainesville, Florida, USA

    Vikas R. Dharnidharka (Associate Professor and Chief Fellowship Program Director Division of Pediatric Nephrology) (Associate Professor and Chief Fellowship Program Director Division of Pediatric Nephrology)

  2. Division of Infectious Diseases Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Michael Green (Professor of Pediatrics and Surgery) (Professor of Pediatrics and Surgery)

  3. Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Steven A. Webber (Professor of Pediatrics, Chief, Division of Cardiology Co-Director, Heart Center Medical Director, Pediatric Heart and Heart-Lung Transplantation) (Professor of Pediatrics, Chief, Division of Cardiology Co-Director, Heart Center Medical Director, Pediatric Heart and Heart-Lung Transplantation)

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Gross, T.G. (2010). Posttransplant Lymphoproliferative Disease (PTLD) in Hematopoietic Stem Cell Transplantation (HSCT). In: Dharnidharka, V.R., Green, M., Webber, S.A. (eds) Post-Transplant Lymphoproliferative Disorders. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-01653-0_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-01653-0_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-01652-3

  • Online ISBN: 978-3-642-01653-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation