Epstein-Barr virus associated post-transplantation lymphoproliferative disorder with hemophagocytosis in a child with Wiskott-Aldrich syndrome

A 23-month-old boy with Wiskott-Aldrich syndrome (WAS) received human leukocyte antigen (HLA)-one locus mismatched, unmanipulated allogeneic bone marrow graft from his mother. An Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disorder (PTLD) of donor cell origin and hemophagocytosis syndrome with fever, lymphadenopathy, hepatosplenomegaly, seizures, involuntary movements and pancytopenia developed 52 days after transplantation. It was difficult to decide on the treatment strategy because the patient presented with B-cell hyperplasia that morphologically appeared malignant but was oligoclonal by heavy-chain analyses. Despite of donor leukocyte transfusion, low dose chemotherapy, and anti-B cell monoclonal antibody immunotherapy, the patient died 107 days after transplantation.     

Epstein-Barr virus-associated posttransplant lymphoproliferative disorder after a cord blood stem cell transplantation presenting with pulmonary nodules

Sixteen months after a cord blood stem cell transplantation, a 6-year-old girl was diagnosed with Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (EBV-PTLD). A CT scan revealed nodules in both lungs, but the patient had neither lymphadenopathy nor other lesions. The diagnosis was confirmed by histopathologic evaluation and the increased level of EBV DNA in the peripheral blood. The patient was successfully treated with rituximab, and a complete regression of the tumors was achieved. This case reveals the need to include EBV-PTLD in the differential diagnosis of pulmonary nodules, as well as demonstrating that rituximab may be effective treatment of EBV-PTLD after cord blood stem cell transplantation.     

儿童EB病毒相关平滑肌肿瘤1例

7岁女性患儿,因双下肢疼痛1年余入院.腰椎MRI提示椎旁团块状软组织肿块;头颅MRI提示双侧海绵窦区结节状肿块;胸部CT示右肺下叶外基底段及左肺上叶前段高密度结节灶.腰椎病变组织病理活检示EB病毒相关平滑肌肿瘤.基因检测示ITK基因存在c.725_730delAGAGTA(p.K242_S243del)新发突变.治疗上...     

B-Cell lymphoproliferative disorder not associated with Epstein-Barr Virus in a child with relapsed acute lymphoblastic leukemia

Lymphoproliferative disorder (LPD) is described in only a few children receiving chemotherapy for cancer. In all of them, an association between LPD and EBV (Epstein-Barr Virus) was found. We report on a patient who developed LPD not associated with EBV while receiving chemotherapy for relapsed acute lymphoblastic leukemia (ALL). Despite discontinuation of chemotherapy, administration of intravenous immunoglobulins and surgery the patient died. Growing experience with this disorder may allow better treatment options in the future and will show whether LPD not associated with EBV requires different therapeutic strategies.     

Wilms tumor in a child with trisomy 13

A 4-year-old black boy with trisomy 13, a history of frequent urinary tract infections, and a horseshoe kidney with painless gross hematuria was examined. An abdominal mass was detected and surgically resected. Examination of the surgical specimen revealed a Wilms tumor. Given the concurrence of trisomy 13 and Wilms tumor and the presence of another such case in the literature, there may be just cause to suspect a locus on chromosome 13 that affects the probability of developing Wilms tumor. Given the increasingly longer survival of patients with trisomy 13, clinicians may need to be aware of the possibility of renal malignant disease in this population of patients.     

Epstein-Barr病毒相关移植后淋巴组织增生性疾病免疫治疗的最新进展

Epstein-Barr病毒相关的移植后淋巴组织增生性疾病(EBV-PTLD)是造血干细胞移植或实体器官移植后病死率极高的并发症。在过去的十年中,对于存在高危因素的患者,免疫治疗干预措施包括减少免疫抑制剂,CD20单克隆抗体(利妥昔单抗)单药治疗或与化疗相结合,输注EBV-特异性T细胞的过继免疫治疗,使得EBV-PTLD患者的存活率有了显著的提高。本文旨在对造血干细胞移植或实体器官移植后EBV-PTLD的高危因素、 临床表现及免疫治疗的最新进展进行总结。     

Epstein-Barr virus-associated lymphoproliferative disease in oral cavity in a renal transplant recipient: a case report

A 10-yr-old child on long-term cyclosporin immunosuppression for a renal transplant presented with gingival swelling enlargement, in a background of gingival hyperplasia. It is tempting to assume that it is a drug-related lesion; perhaps, an area of plaque-related inflammation. An incisional biopsy revealed a monomorphic B-cell post-transplant lymphoproliferative disease (PTLD). At this stage, high Epstein-Barrr virus (EBV) titres supported a diagnosis of EBV-driven PTLD. Despite discontinuation of cyclosporin and reduction of EBV viral load to undetectable levels, there was considerable enlargement of the tumour. The patient underwent six courses of cyclophosphamide, vincristine and prednisolone chemotherapy. This resulted in a dramatic reduction in the size of the right mandibular mass with complete mucosal healing intra-orally. Her renal transplant still has good function and there is no evidence of PTLD recurrence 23 months after initial diagnosis. This case illustrates that PTLD can manifest in unusual sites and in transplant recipients on cyclosporin immunosuppression it is easy to assume that any gingival hyperplasia is drug induced; however, the differential diagnosis of gingival hyperplasia should include PTLD.     

Epstein-Barr virus-associated lymphoma in a child undergoing an autologous stem cell rescue

Epstein-Barr virus-associated lymphoproliferative disease (EBV-LPD) is a serious disorder seen in various states of immunodeficiency, often with a fatal outcome. In this article, a patient with EBV-lymphoma after autologous stem cell rescue for treatment of a nonhematologic solid tumor is described. The child, a 4-year-old boy, had unilateral retinoblastoma with metastatic spread to the central nervous system. He had previously received both local tumor bed and craniospinal radiation therapy together with intensive myeloablative alkylator chemotherapy before autologous stem cell rescue. Histologically confirmed lymphoma with evidence of active EBV proliferation developed within cervical lymph nodes 3 weeks after his first autologous stem cell rescue. A complete clinical remission of the lymphadenopathy was obtained after infusions of rituximab (an anti-CD20 monoclonal antibody), acyclovir, and high-titer anticytomegalovirus immunoglobulin. The patient died approximately 6 months later of persistent and progressive retinoblastoma without any clinical evidence of lymphoma. It is concluded that EBV-LPD should be included in the differential diagnosis in patients in whom lymphadenopathy develops after autologous stem cell rescue.     

Emerging therapeutic strategies for Epstein-Barr virus+ post-transplant lymphoproliferative disorder

De novo malignancies represent an increasing concern in the transplant population, particularly as long-term graft and patient survival improves. EBV-associated B-cell lymphoma in the setting of PTLD is the leading malignancy in children following solid organ transplantation. Therapeutic strategies can be categorized as pharmacologic, biologic, and cell-based but the variable efficacy of these approaches and the complexity of PTLD suggest that new treatment options are warranted. Here, we review current therapeutic strategies for treatment of PTLD. We also describe the life cycle of EBV, addressing the viral mechanisms that contribute to the genesis and persistence of EBV+ B-cell lymphomas. Specifically, we focus on the oncogenic signaling pathways activated by the EBV LMP1 and LMP2a to understand the underlying mechanisms and mediators of lymphomagenesis with the goal of identifying novel, rational therapeutic targets for the treatment of EBV-associated malignancies.     

Epstein-Barr virus-associated post-transplant lymphoproliferative disease after bone marrow transplantation mimicking graft-versus-host disease

In contrast to solid organ transplantation (Tx), the incidence of post-transplant lymphoproliferative disease (PTLD) after hematopoietic stem cell Tx (HSCT) is generally low. This risk, however, is significantly elevated in patients receiving human leukocyte antigen (HLA) mis-matched or T-cell-depleted grafts, or after treatment for severe graft-versus-host disease (GvHD). An 18-yr-old patient with positive Epstein-Barr virus (EBV) serology received a fully matched, unmanipulated bone marrow graft from an unrelated EBV-positive donor for treatment of acute myeloid leukemia (AML) in second complete remission. GvHD prophylaxis was performed with cyclosporin A (CsA) and a short course of methotrexate. Four months after Tx, the patient developed ulcerative tonsillitis that was unresponsive to antibiotic treatment. Diarrhea appearing simultaneously was interpreted as gastrointestinal GvHD and steroids were added to CsA. A few days later the patient was admitted to hospital because of generalized seizure and pneumonia. Despite reduction of immunosuppression, intensification of anti-viral treatment, and subsequent mechanical ventilation, the patient died of acute respiratory distress 6 days later. Autopsy demonstrated disseminated EBV-induced, multi-nodular lymphoma infiltration of the entire colon but no signs of GvHD. Moreover, both lungs, paratracheal lymph nodes, kidneys, thyroid gland, and liver were infiltrated with large B-cell non-Hodgkin's lymphomas. This case underlines the rapid and aggressive course of EBV-induced disseminated PTLD after HSCT, initially mimicking intestinal GvHD because of massive colonic lymphoma infiltration. Tissue biopsies should be performed early for establishing correct diagnosis, thus enabling specific therapy, e.g. infusion of donor leukocytes with cytotoxic T-lymphocytes.     

Catastrophic intracerebral hemorrhage in a young infant with Wilms tumor

We present a 7-month-old male infant with stage I Wilms tumor who unexpectedly died from a catastrophic intracerebral hemorrhage, 4 months after completion of chemotherapy and complete surgical resection of the tumor. The precise etiology underlying the fatal event remains unclear as postmortem was refused, but we postulate spontaneous hemorrhage from an underlying cerebral vascular malformation as the most likely cause, which led to the child's unfortunate demise. Although extremely rare, cerebral vascular anomalies have previously been reported in children with Wilms tumor. The coexistence of the 2 uncommon disorders may be related to their congenital origin. Wilms tumor diagnosed in very young infants have clinical and morphologic attributes that do not pertain in older children and the risk of associated congenital anomalies is also much higher among those discovered in the first year of life. This raises the question whether routine magnetic resonance imaging should not be performed in infants less than a year with Wilms tumor, as part of the initial evaluation, to exclude cerebral metastases and underlying vascular malformations.