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Late onset of EBV-driven PTLD/Burkitt lymphoma/leukemia in a patient 10 years after allogeneic stem cell transplant for AML

Bone Marrow Transplantation volume 45, pages 191–194 (2010)Cite this article

Post-transplant lymphoproliferative disorder (PTLD) is a well defined, distinctive clinicopathological entity and is composed of a heterogeneous group of monoclonal or polyclonal lymphoproliferative lesions that occur exclusively in iatrogenically immunosuppressed recipients following solid organ or BMT.1 Clinically and pathologically, PTLDs represent a spectrum of diseases ranging from early Epstein Barr virus (EBV)-driven polyclonal B-cell proliferation to morphological and genetic/molecular defined malignant lymphomas.1, 2 Transplant patients have a 50–100 fold increased prevalence of B-cell lymphoma.1, 2, 3, 4 There is an overall incidence of 1–5% in solid-organ transplant recipients and of 1% in marrow transplant recipients.1, 3, 4 However, patients who receive HLA-mismatched or T-cell depleted BM and those who receive anti-CD3 MoAB therapy for GVHD after transplant are at the highest risk for development of PTLD/lymphoma.5 As such, patients typically present with widespread disease clinically and have a very poor prognosis. A higher proportion of BM transplant patients with PTLD die of their disease than do solid-organ allograft recipients.1, 3, 4, 5, 6 In a retrospective analysis of 854 allogeneic transplants over a period of 8.5 years in a single institution, an incidence of 3% EBV reactivation was noted, with a 1.3% incidence of EBV-PTLD, with a mortality rate of 82%. Over 90% of the cases occurred within the first year of transplant.6

Here we report an extremely rare, unique case of very late onset, lethal EBV-driven PTLD manifested as a typical Burkitt lymphoma/leukemia involving the BM and liver in a patient 10-year status post-allogeneic BMT for his refractory AML. The patient is a 61-year-old male with a history of primary refractory AML who underwent un-manipulated Allo-SCT from his HLA-identical brother after a myeloablative, fractionated TBI-based conditioning regimen in 1998. Post-transplant complications included extensive chronic GVHD involving the skin, oral cavity and possibly lung. The chronic GVHD was managed conservatively with tacrolimus and mycophenolate for several years, until the patient refused all immunosuppressive medication from 2005 to 2008. Approximately 1 year before the current presentation, the patient developed respiratory symptoms, which prompted an evaluation with bronchoalveolar lavage, with the isolation of both Nocardia asteroids and Aspergillus fumigatus. He was treated successfully with minocycline and voriconazole. A flare in symptoms including fatigue, weight loss and mouth discomfort, prompted a trial of re-institution of immunosuppression with low-dose prednisone and tacrolimus. After 6 weeks, the patient presented with Gram-negative bacteremia, and quickly developed pancytopenia (hemoglobin 9.3 g per 100 ml, WBC 3600/μl, plts 20 000/μl) with elevated liver enzymes, and very high serum lactate dehydrogenase level (15 041 U/l). On computed tomography scan of the chest, abdomen and pelvis, innumerable small lesions were seen throughout the liver without evidence of lymphadenopathy or splenomegaly. A BM biopsy was performed to rule out relapsed AML.

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Authors and Affiliations

  1. Department of Pathology, City of Hope, Duarte, CA, USA

    Q Huang, Y Lu & M L Slovak

  2. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, USA

    L Popplewell & S J Forman

  3. Department of Hematology, Ningbo #1 Hospital, Ningbo, PR China

    Y Lu

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Correspondence to Q Huang.

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Huang, Q., Popplewell, L., Lu, Y. et al. Late onset of EBV-driven PTLD/Burkitt lymphoma/leukemia in a patient 10 years after allogeneic stem cell transplant for AML. Bone Marrow Transplant 45, 191–194 (2010). https://doi.org/10.1038/bmt.2009.86

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