Epstein–Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond–Blackfan anemia

Ohga, Shouichi; Kanaya, Yoshiaki; Maki, Hiromi; Takada, Hidetoshi; Ohshima, Koichi; Kanda, Motonobu; Nomura, Akihiko; Suminoe, Aiko; Matsuzaki, Akinobu; Hara, Toshiro

doi:10.1038/sj.bmt.1702138

Cited by 30 publications

(14 citation statements)

References 24 publications

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“…22 In this particular case the tumor tissue was confirmed to be of donor origin by HLA typing, and as opposed to the case reported by Ohga et al, 2 EBV DNA was identified in the cord blood using PCR. Neither of these results provides conclusive evidence of the UCB as the source of the EBV infection in this case.…”

Section: Discussionmentioning

confidence: 74%

Detection of EBV DNA in the cord blood donor for a patient developing Epstein–Barr virus-associated lymphoproliferative disorder following mismatched unrelated umbilical cord blood transplantation

Haut

Kovarik

Shaw

et al. 2001

Bone Marrow Transplant

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Summary:Epstein-Barr virus-associated post-transplant lymphoproliferative disorder (PTLD) has been well described as a complication following allogeneic stem cell transplantation but has only recently been reported following umbilical cord blood (UCB) transplant. We report the case of a child transplanted with unrelated mismatched UCB for juvenile chronic myelogenous leukemia (JCML) who developed EBV-associated PTLD, which was confirmed pathologically, 139 days following stem cell infusion. There was no clinical response to reduction of immune suppression, high-dose acyclovir, or alpha interferon. The patient died 160 days after transplantation. EBV was detected by polymerase chain reaction in the cord blood unit used for transplantation. This case demonstrates that EBV-associated PTLD can occur following mismatched unrelated UCB transplant and may be related to transmission of EBV infection by donor lymphocytes. Bone Marrow Transplantation (2001) 27, 761-765. Keywords: PTLD; umbilical cord blood; transplant; EBV Epstein-Barr virus (EBV)-associated PTLD has been well described as a complication following allogeneic stem cell transplantation but has only recently been reported following UCB transplantation. 1,2 The overall incidence of PTLD in patients who undergo hematopoietic stem cell transplant varies with donor stem cell source, degree of HLA matching, type of graft-versus-host disease (GVHD) prophylaxis, primary underlying disease, and type of graft manipulation. 1 Patients with primary immunodeficiencies transplanted with an unrelated HLA mismatched, T cell-depleted graft are at the highest risk with a probability of developing EBV-associated PTLD that may be as high as 65%. Umbilical cord blood has heretofore been considered a pristine source of EBV-uninfected stem cells. We describe the case of a child who developed EBV-associated PTLD following hematopoietic stem cell transplantation from an unrelated mismatched cord blood donor with evidence of EBV DNA in the cord blood, which was identified only after the child's death. Case reportA 29-month-old Hispanic boy with JCML at 19 months of age underwent stem cell transplantation with mismatched unrelated UCB 3 months after presentation. The UCB unit was an HLA-A and -B serologic match with a mismatch at the DR locus by high-resolution DNA testing. Viral serologic testing at the time of diagnosis of JCML revealed negative VCA-IgM and VCA-IgG EBV antibody titers, and positive IgG but negative IgM antibody titers to CMV indicating past infection. Repeat EBV serologies prior to transplantation, after blood and platelet transfusions, showed low levels of VCA-IgG, but no VCA-IgM. Serologic tests for varicella-zoster virus, hepatitis A, B, and C, and HIV were negative.The conditioning regimen included total body irradiation 150 cGy twice daily for 4 days, thiotepa 10 mg/kg on day −6, etoposide 1000 mg/m 2 by continuous infusion over 24 h on days −6 and −5 (total dose 2000 mg/m 2 ), and cyclophosphamide 60 mg/kg once daily i.v. on days −4, −3, and −2 (total dose 18...

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Section: Discussionmentioning

confidence: 74%

Detection of EBV DNA in the cord blood donor for a patient developing Epstein–Barr virus-associated lymphoproliferative disorder following mismatched unrelated umbilical cord blood transplantation

Haut

Kovarik

Shaw

et al. 2001

Bone Marrow Transplant

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“…Despite the widespread prevalence of EBV infection, EBV has been directly implicated in the development of only two malignancies observed in relatively restricted geographic areas: Burkitt's Lymphoma in East Africa and nasopharyngeal carcinoma in Southern China. It has also been closely associated to Hodgkin's Disease, thymic lymphoepithelioma, opportunistic B-cell lymphomas, pleural B-cell lymphomas or pyothorax associated B-cell lymphomas, opportunistic T-cell and NK-cell lymphomas in immunodeficiencies, primary nasal T-cell and NK-cell lymphomas, gastric carcinoma, and most recently, invasive breast carcinoma (1)(2)(3)(4)(5)(6)(7)(8)(9).…”

Section: Epstein-barr Virus (Ebv) Is a Common Humanmentioning

confidence: 99%

Detection of Epstein-Barr Virus in Rapidly Growing Fibroadenomas of the Breast in Immunosuppressed Hosts

et al. 2002

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Fibroadenomas are the most common benign tumors of the female breast and are associated with a slight increase in the risk of subsequent breast cancer. Multiple fibroadenomas have been described in patients after renal transplantation and are thought to be secondary to drug-related growth stimulation. Epstein-Barr virus (EBV) has been detected in many neoplasms, including breast cancer. We set out to investigate whether EBV plays a role in the development of rapidly growing fibroadenomas in immunocompromised patients. We studied 19 fibroadenomas and one invasive ductal carcinoma that developed after organ transplantation or treatment for lupus erythematosus. As a control group we included 11 fibroadenomas from non-immunocompromised patients. DNA was amplified using polymerase chain reaction (PCR) of the EBV-encoded small RNA (EBER-2) DNA sequence. EBV latent membrane protein 1 (LMP-1) transcripts were amplified using reverse transcription (RT) PCR. Immunohistochemical (IHC) staining for LMP-1 protein was performed. A total of 9 out of 20 tumors (45%) were concordantly positive by PCR and IHC. IHC stained exclusively the epithelial cells. All the fibroadenomas in non-immunocompromised patients were negative for LMP-1 (Fisher's exact test P ‫؍‬ .0006). These data suggest that EBV is associated with fibroadenomas in this immunosuppressed population and that the infection is specifically localized to epithelial cells. This is the first study suggesting a role for EBV in the pathogenesis of fibroadenomas.

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“…[3][4][5][6][7] More recently, Brunstein et al at the University of Minnesota investigated the incidence of EBV-related complications in 335 patients undergoing CBT and documented an overall rate of 4.5% (total 15 cases, with 5 adults) with an incidence of 3.3% in recipients of myeloablative transplantations, 7% for nonmyeloablative transplantations and up to 21% among the subset of patients who received also ATG, suggesting a significantly higher risk of EBV-related complications in recipients of a nonmyeloablative preparative regimen with ATG. 8 The lower incidence of EBV-viremia and PTLD reported in earlier series may, at least in part, be related to the recent introduction of effective and highly sensitive techniques for quantitative measurements of EBV load and sequential monitoring of EBV reactivation.…”

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confidence: 99%

“…Fifty-six of these patients had participated in registrational trials and the results of tumor response and toxicity (but not related to ALC) are included in previous publications. 4 Rituximab-refractory patients were classified as patients who did not respond or relapsed within 6 months of rituximab therapy before ibritumomab tiuxetan therapy. All patients were treated with 90 Y ibritumomab tiuxetan 0.4 mCi/kg (maximum of 32 mCi) as described previously.…”

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confidence: 99%

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Assessment of cellular origin and EBV status in a PTLD after double cord blood transplantation

Reddiconto¹,

Chiusolo²,

Fiorini³

et al. 2007

Leukemia

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Epstein–Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond–Blackfan anemia

Cited by 30 publications

References 24 publications

Detection of EBV DNA in the cord blood donor for a patient developing Epstein–Barr virus-associated lymphoproliferative disorder following mismatched unrelated umbilical cord blood transplantation

Detection of EBV DNA in the cord blood donor for a patient developing Epstein–Barr virus-associated lymphoproliferative disorder following mismatched unrelated umbilical cord blood transplantation

Detection of Epstein-Barr Virus in Rapidly Growing Fibroadenomas of the Breast in Immunosuppressed Hosts

Assessment of cellular origin and EBV status in a PTLD after double cord blood transplantation

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