Birte Wistinghausen

A hybrid strategy for the prevention of cytomegalovirus-related complications in pediatric liver transplantation recipients.

Background. This single center, retrospective study describes experience with a hybrid prevention strategy combining short-course antiviral prophylaxis and preemptive cytomegalovirus (CMV) polymerase chain reaction (PCR) monitoring. Methods. One hundred twenty-two pediatric liver transplantation recipients were followed up for a median of 2.3 years posttransplantation. Subjects received a minimum of 14 days of postoperative ganciclovir, followed by monthly CMV PCR monitoring. Results. Forty-three CMV seronegative recipients received seropositive grafts and were considered high risk for CMV; 79 subjects were routine risk. CMV was detected by PCR in the absence of symptoms in 34.4% of subjects and was more likely in high risk than in routine risk recipients (58.1% vs. 21.8%, P=0.0001). Twelve subjects (9.8%) developed CMV disease (8 high risk vs. 4 routine risk, P=0.03). Three subjects developed acute rejection in the 6 months after detection of CMV, but CMV was preceded by rejection in 13 subjects. There were no mortalities secondary to CMV. A total of 38.5% of subjects were spared antiviral medications beyond their initial postoperative prophylaxis. Conclusions. These results suggest that a hybrid preventative approach for CMV is a reasonable alternative to prolonged antiviral prophylaxis and may reduce unnecessary exposure to antiviral therapy. However, patients who receive intensified immunosuppression after acute rejection are at increased risk for CMV and may require extended prophylaxis and closer monitoring.

Post-Transplant Lymphoproliferative Disease in Pediatric Solid Organ Transplant Recipients

Post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients has become one of the most common forms of lymphoproliferation in childhood and is a serious complication of SOT. More than 90% of cases are of B-cell origin, Epstein Barr virus (EBV) positive and are mostly occurring in the early post-transplant period. Pathologically and clinically it is a heterogenous disease ranging from being responsive to reduced immunosuppression without further intervention to rapidly progressive fulminant PTLD requiring prompt initiation of therapy. Prognosis overall is favorable. Current treatment strategies as well new promising targeted immune-based therapies such as rituximab and EBV-specific cytotoxic T-lymphocytes are being discussed.

Autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura in pediatric solid organ transplant recipients, report of five cases and review of the literature

Miloh T, Arnon R, Roman E, Hurlet A, Kerkar N, Wistinghausen B. Autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura in pediatric solid organ transplant recipients, report of five cases and review of the literature. 
Pediatr Transplantation 2011: 15: 870–878.

Epstein-Barr virus-associated smooth muscle tumors in children following solid organ transplantation: a review.

EBV‐SMT are a rare entity following organ transplantation. Given the rarity of the tumor, there is no standard approach to diagnosis and treatment. A literature search identified 28 reported cases of EBV‐SMT in addition to our own experience with one case. The aim of this review is to summarize the existing data regarding pathogenesis, diagnosis, and treatment.

Long-term remission in a child with refractory EBV + hydroa vacciniforme-like T-cell lymphoma through sequential matched EBV + -related allogeneic hematopoietic SCT followed by donor-derived EBV-specific cytotoxic T-lymphocyte immunotherapy

Long-term remission in a child with refractory EBV + hydroa vacciniforme-like T-cell lymphoma through sequential matched EBV + -related allogeneic hematopoietic SCT followed by donor-derived EBV-specific cytotoxic T-lymphocyte immunotherapy

Identifying predictive factors for posttransplant lymphoproliferative disease in pediatric solid organ transplant recipients with Epstein-Barr virus viremia.

Epstein-Barr virus (EBV) viremia (EV) in pediatric solid organ transplant (SOT) recipients is a significant risk factor for posttransplant lymphoproliferative disease (PTLD) but not all patients with EV develop PTLD. We identify predictive factors for PTLD in patients with EV. We conducted a retrospective chart review of all pediatric SOT recipients (0 to 21 y) at a single institution between 2001 and 2009. A total of 350 pediatric patients received a SOT and 90 (25.7%) developed EV. Of EV patients, 28 (31%) developed PTLD. The median age at transplant was 11.5 months in the PTLD group and 21.5 months in the EV-only group (P=0.003). Twenty-three (37%) EV-only patients had immunosuppression increased before EV, compared with 28 (100%) of PTLD patients (P<0.001). The median peak EBV level was 3212 EBV copies/105 lymphocytes for EV-only and 8392.5 EBV copies/105 lymphocytes for PTLD (P=0.005). All patients who developed PTLD had ≥1 clinical symptoms. Younger age at transplant, increased immunosuppression before EV, higher peak EBV level, and presence of clinical symptoms have predictive value in the development of PTLD in SOT patients with EV.

Graft rejection in pediatric liver transplant patients with Epstein‐Barr viremia and post‐transplant lymphoproliferative disease

Weiner C, Weintraub L, Wistinghausen B, Tomaino J, Arnon R, Kerkar N, Miloh T. Graft rejection in pediatric liver transplant patients with Epstein‐Barr viremia and post‐transplant lymphoproliferative disease.

Fulminant Liver Failure in a Child With β-Thalassemia on Deferasirox: A Case Report.

Deferesirox (DFX), an oral chelating agent, is used to treat chronic iron overload in several hematological diseases such as β-thalassemia, sickle cell disease, and myelodysplastic anemia. DFX is generally well tolerated with the exception of gastrointestinal disturbances and rash, although cases of renal toxicity, as well as acute and chronic liver failure, have been reported in adults and children. Here we describe a 3-year-old girl with β-thalassemia undergoing treatment with DFX who presented with acute liver failure and Fanconis syndrome. It is important for pediatric gastroenterologists, hepatologists, and hematologists to be aware that the commonly used drug DFX can lead to acute liver failure in children, and liver function should be monitored closely in all patients taking DFX.

Metastatic osteosarcoma presenting as a singlepulmonary microembolus

There are only a few published reports of tumor emboli from osteosarcoma. We are reporting a 17-year-old adolescent boy with a history of localized osteosarcoma who developed a symptomatic pulmonary artery tumor embolus. He was initially diagnosed with a pulmonary thromboembolism. This is the first reported case of a single tumor embolus developing after surgical resection of a tumor with 100% necrosis after chemotherapy and no evidence of metastatic disease at the time of surgery. Pulmonary tumor embolism should be considered in the differential diagnosis in patients with cancer who present with dyspnea. The differentiation of tumor embolus from other causes of dyspnea is important for treatment plan.

Genomic characterization of pediatric B-lymphoblastic lymphoma and B-lymphoblastic leukemia using formalin-fixed tissues

Recurrent genomic changes in B‐lymphoblastic leukemia (B‐ALL) identified by genome‐wide single‐nucleotide polymorphism (SNP) microarray analysis provide important prognostic information, but gene copy number analysis of its rare lymphoma counterpart, B‐lymphoblastic lymphoma (B‐LBL), is limited by the low incidence and lack of fresh tissue for genomic testing.