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:

EBV-positive lymphoproliferative disease with medullary, splenic and hepatic infiltration after imatinib mesylate therapy for chronic myeloid leukemia

Leukemia volume 21, pages 2208–2210 (2007)Cite this article

Imatinib mesylate has considerably changed the management of chronic myeloid leukemia (CML) in the chronic phase and has increased the rates of complete cytogenetic remission (CCR)1 and major molecular remission.2 Although it has few toxic effects, unusual side effects have been observed such as the appearance of gray hair during treatment.3 In 2003, the first case of Epstein–Barr Virus (EBV)-positive cutaneous B-cell lymphoproliferative disease after imatinib mesylate therapy was reported.4 We report a case of disseminated EBV-positive lymphoproliferative disease with no correction when imatinib was discontinued, multiple relapses and resistance to rituximab.

A 59-year-old woman was treated with imatinib mesylate (400 mg/day) for chronic phase CML in April 2003. Complete hematological response was achieved after 1 month, CCR after 6 months and complete molecular response (CMR) after 2 years. After 30 months of imatinib mesylate treatment, the patient was still in CMR but suddenly exhibited a decrease in performance status with fever, night sweats, pancytopenia and disseminated intravascular coagulation. She was receiving her usual medication including inhaled beta-2 agonist and inhaled cortisone, since she had a history of asthma. Clinical examination revealed no adenomegaly but there was a huge hepatomegaly (26 cm) and splenomegaly (19.5 cm) confirmed by CT scan. Bone marrow biopsy revealed EBV-positive lymphoproliferative disease characterized by a granulomatous infiltrate containing large immunoblastic cells with pro-eminent nucleoli. Immunostaining showed that these neoplastic cells were positive for CD30, CD20, CD79a and EBV/LMP1, but negative for CD15. In situ hybridization for Epstein-Barr Virus PNA probe/fluoresceine (EBER) DAKO Y 5200 Denmark (EBV-EBER) sequences was positive on these cells. A liver biopsy confirmed hepatic infiltration by the neoplastic cells. Serum EBV quantification by polymerase chain reaction (PCR) was highly positive with 92.140 DNA copies/mm3. Viral serologies were negative for HIV but positive for cytomegalovirus (CMV) and EBV. Lymphocyte count was 1520/mm3 with normal CD4+ (1300/mm3) and a low CD8+ subpopulation (122/mm3). Since discontinuation of imatinib for 17 days did not improve the patient's performance status or cytopenia, intravenous rituximab 375 mg/m2 was given weekly for 4 weeks. After two rituximab injections, clinical remission was observed and EBV quantification was negative (<500 copies of EBV/mm3). One month after the rituximab therapy, a complete response persisted with negative EBV quantification, so imatinib mesylate was reintroduced.

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

Figure 1
Figure 2
Figure 3

References

  1. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2003; 348: 994–1004.

    Article  CAS  Google Scholar 

  2. Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML et al. Frequency of major molecular responses to imatinib or interferon alpha plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med. 2003; 349: 1423–1432.

    Article  CAS  Google Scholar 

  3. Etienne G, Cony-Makhoul P, Mahon FX . Imatinib mesylate and gray hair. N Engl J Med. 2002; 347: 446.

    Article  Google Scholar 

  4. Bekkenk MW, Vermeer MH, Meijer C, Jansen P, Middeldorp J, Stevens S et al. EBV-positive cutaneous B-cell lymphoproliferative disease after imatinib mesylate. Blood 2003; 102: 4243.

    Article  CAS  Google Scholar 

  5. Gross TG, Steinbuch M, DeFor T, Shapiro RS, McGlave P, Ramsay NKC et al. B cell lymphoproliferative disorders following hematopoietic stem cell transplantation: risk factors, treatment and outcome. Bone Marrow Transplant. 1999; 23: 251–258.

    Article  CAS  Google Scholar 

  6. Seggewiss R, Lore K, Greiner E, Magnusson MK, Price DA, Douek DC et al. Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner. Blood 2005; 105: 2473–2479.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Service des maladies du sang, Hôpital du Haut-Lévèque, Pessac, France

    T Leguay, C Foucaud, K Bouabdallah, R Tabrizi, G Marit, A Pigneux & N Milpied

  2. Laboratoire d'Anatomo-pathologie, Hôpital du Haut-Lévèque, Pessac, France

    M Parrens & M A Belaud-Rotureau

  3. Service d'Oncologie, Clinique Bordeaux-Nord, Bordeaux, France

    O Fitoussi

Authors
  1. T Leguay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Foucaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Parrens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O Fitoussi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Bouabdallah
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M A Belaud-Rotureau
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R Tabrizi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G Marit
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Pigneux
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. N Milpied
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Milpied.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leguay, T., Foucaud, C., Parrens, M. et al. EBV-positive lymphoproliferative disease with medullary, splenic and hepatic infiltration after imatinib mesylate therapy for chronic myeloid leukemia. Leukemia 21, 2208–2210 (2007). https://doi.org/10.1038/sj.leu.2404758

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404758

This article is cited by

Search

Advanced search

Quick links