Donor lymphocyte transfusion for the treatment of Epstein–Barr virus-associated lymphoproliferative disorder of the brain

Abstract

Summary:EBV-associated lymphoproliferative disorder (LPD) is a rare but serious complication in marrow transplant recipients. A 31-year-old Japanese woman in the second chronic phase of CML received an allogeneic BMT from her HLA 2-locus-incompatible 62-year-old father. Around day +200, she developed EBV-LPD of the right parieto-temporal lobe which caused slowly progressive left hemiparesis. Two courses of donor lymphocyte transfusions (DLT) of 10 6 CD3 + T cells/kg of body weight failed to suppress her central nervous system (CNS) EBV-LPD. The patient died of recurrent blastic crisis of CML. This case suggests that DLT may be ineffective for the treatment of CNS EBV-LPD. Keywords: Epstein-Barr virus-associated lymphoproliferative disorder; donor lymphocyte transfusion; central nervous system EBV-associated lymphoproliferative disorder (LPD) is a rare but serious complication in marrow transplant recipients. 1,2 Although there are reports of successful treatment of polyclonal or oligoclonal proliferations with agents such as interferon-␣ and intravenous ␥-globulin, high-dose acyclovir, and anti-B-cell MoAb, 3-5 monoclonal disease has remained refractory to treatment in marrow transplant recipients.Recently, donor lymphocyte transfusions (DLT) have been shown to be an effective treatment for EBV-LPD. 6,7 We report the case of a Japanese woman, who developed EBV-LPD of the right cerebrum following allogeneic BMT and who was then treated with DLT. Case reportA 31 year-old Japanese woman was admitted to our hospital for the treatment of myeloid blastic crisis (BC) of CML Correspondence: Dr K Nagafuji, Department of Hematology, Hara Sanshin General Hospital, 1-8 Taihaku-machi, Hakata-ku, Fukuoka 812, Japan Received 4 August 1997; accepted 22 December 1997 in July 1996. She entered the second chronic phase after treatment with vincristine and prednisolone. The patient had no HLA-identical siblings, nor were there any HLAidentical unrelated donors in the Japan Marrow Donor Program. Because of the poor prognosis in BC, we decided to perform a BMT using her HLA 2-locus-incompatible 62-year-old father as donor. The donor was seropositive for human T cell leukemia virus type 1 (HTLV-1), while the recepient was seronegative. 8 Both the recipient and the donor were seropositive for EBV (VCA IgG ×40 VCA IgM Ͻ×10 EBNA ×10, VBCA IgG ×640 VCA IgM Ͻ×10 EBNA ×10, respectively).The pre-transplant conditioning consisted of BU 4 mg/kg orally in divided doses daily on days −8 to −5, and CY 50 mg/kg i.v. daily on days −4 to −2. Because of ABO major incompatibility, bone marrow mononuclear cells isolated by density-gradient centrifugation (1.8 × 10 8 /kg of body weight) were given. Tacrolimus (FK506; Fujisawa, Osaka, Japan) in combination with MTX was used for GVHD prophylaxis. Grade II GVHD of the skin developed on day +11 but this responded well to high-dose methylprednisolone therapy. Granulocytes exceeded 0.5 × 10 9 /l on day +16, and platelets exceeded 50 × 10 9 /l on day +26. Prolonged administration of immunosuppressive agents wa...

Discrepancy in EBV-DNA load between peripheral blood and cerebrospinal fluid in a patient with isolated CNS post-transplant lymphoproliferative disorder

“…Isolated CNS PTLD is extremely rare: to the best of our knowledge, only six cases have been reported [9][10][11][12][13][14]. In two of the reported cases, both PB and CSF were examined for EBV-DNA load: one was negative in both serum and CSF [12], but the other showed positive in both [13].…”

Primary central nervous system post-transplant lymphoproliferative disorders following allogeneic hematopoietic stem cell transplantation

“…Primary CNS-PTLD following allo-HSCT presents a particular challenge as there is limited clinical experience, few reported cases and lack of prospective studies. Only a small number of cases isolated CNS-PTLD following allo-HSCT have been reported [10][11][12][13][14][15][16][17][18] (Table 1). The latency between transplantation and development of CNS-PTLD ranged from 2 to 23 months.…”

A phase 1/2 trial of arginine butyrate and ganciclovir in patients with Epstein-Barr virus–associated lymphoid malignancies

“…66 Adoptive immunotherapy, including infusion of donor leukocytes or EBVspecific donor-type T-cell lines, has been used and may be effective in some, but may be ineffective in advanced cases of PTLD, or in disease with CNS involvement. 67,68 The administration of monoclonal antibodies against B-cell epitopes such as CD20 has produced responses in some cases of PTLD but not in others. 69 Monoclonal antibodies directed against this B-cell epitope are also used in the treatment of B-cell NHL.…”