Monitoring of adenovirus (ADV)-specific T cells in a boy with ADV pneumonia and disseminated disease after lung transplantation.

Human adenovirus (ADV) infections are the cause of severe morbidity and mortality in transplant recipients. Cidofovir (CDV) is the current standard antiviral treatment. We report the case of a 3-year-old boy after lung transplantation with severe ADV sepsis, who was monitored for ADV-specific T cells during his disease and recovery. A strong increase in ADV-specific T cells was accompanied by resolution of ADV in blood and bronchoalveolar lavage fluid. Antiviral treatment with CDV was individually adapted according to anti-ADV immune responses, which provides a new method for tailoring antiviral treatment in lung transplant recipients.

Normalized transcranial Doppler velocities, stroke prevention and improved pulmonary function after stem cell transplantation in children with sickle cell anemia.

BACKGROUND: Abnormal transcranial Doppler velocities (TCD) indicate an increased risk of stroke in patients with sickle cell anemia (SCA) and require regular blood transfusions. Hematopoietic stem cell transplantation (HSCT) is under discussion as an alternative to chronic transfusion in these patients. PATIENTS AND METHODS: This retrospective analysis includes 9 patients with SCA undergoing HSCT at a single center in Germany. Special focus was given to the neurologic follow-up and to the results of TCD studies. RESULTS: High risk of stroke or previous stroke was an HSCT-indication in 8 of 9 patients, although most patients had more than one indication for HSCT. TCD was normalized in all 5 patients after HSCT in whom this test was available. None of the patients developed a stroke after HSCT. No further strokes occurred even in patients that experienced recurrent strokes during chronic transfusion before HSCT. 2 of the 9 patients received a 10/10 HLA-matched unrelated donor graft, the others matched related grafts.All patients were alive, free of SCA symptoms and transfusion-independent with stable chimerism 3-11 years after HSCT. Pulmonary function tests normalized in 1 patient with severe sickle cell lung disease. CONCLUSION: HSCT is able to prevent stroke in patients with SCA. Its perspectives and limitations should be discussed early during the treatment of a patient with complicated SCA.

Molecular and clinicopathological analysis of Epstein-Barr virus-associated posttransplant smooth muscle tumors.

Epstein-Barr virus (EBV)-associated posttransplant smooth muscle tumors (PTSMT) are very rare complications. We aimed to provide a clinicopathological characterization which is based on our own case series (n = 5) as well as previously reported PTSMT cases (n = 63). Meta-analysis of PTSMT and molecular analysis of tumor cells from our cohort was performed. Most PTSMT developed in kidney-transplanted patients (n = 41/68, 60%). Liver/transplant liver was the main site of manifestation (n = 38/68, 56%). Tumors occurred after a median interval of 48 months (range 5-348) and developed earlier in children than in adults. Most tumors showed no marked cellular atypia, low mitosis rate and no tumor necrosis. Gene expression analysis of 20 EBV-related genes, including two microRNAs, revealed overexpression of MYC (p = 0.0357). Therapy was mainly based on surgical resection or reduced immunosuppression but no significant differences in overall survival were evident. Lower overall survival was associated with multiorgan involvement (n = 33/68, 48.5%) and particularly with intracranial PTSMT manifestation (n = 7/68, 10%; p < 0.02), but not transplant involvement (n = 11/68, 16%). In summary, PTSMT differ from conventional leiomyosarcomas by their lack of marked atypia, unusual sites of involvement and defining EBV association. Surgery and reduced immunosuppression show comparable clinical results and prognosis is associated with intracranial manifestation.

CXCL13 as a novel marker for diagnosis and disease monitoring in pediatric PTLD.

Posttransplant lymphoproliferative disease (PTLD) is a severe complication of immunosuppressive treatment in organ-grafted children. Early diagnosis of PTLD is hampered by both unspecific clinical symptoms and lack of easy accessible markers. The homeostatic chemokine CXCL13, which plays a crucial role in B-cell homing and lymphoid organ development, is expressed in some lymphomatous diseases. This study aims to investigate whether serum CXCL13 (sCXCL13) levels correlate with occurrence and regression of PTLD in pediatric solid-organ graft recipients. Serum samples from PTLD patients (n = 21), patients with Epstein-Barr virus (EBV) reactivation (n = 18), and healthy age-matched controls (n = 19) were tested for CXCL13 using a commercially available ELISA kit. sCXCL13 levels were significantly higher in PTLD patients than in healthy children. PTLD patients had also higher sCXCL13 values than pediatric solid-organ recipients with EBV reactivation. An increase in sCXCL13 levels was observed from EBV reactivation to PTLD diagnosis in most cases. Elevated sCXCL13 levels were detected up to 2 years prior to PTLD diagnosis and correlated well with response to cytoreductive treatment in individual patients. sCXCL13, thus, may be a readily available surrogate marker for the diagnosis of PTLD and for monitoring of response to treatment in patients with initially elevated sCXCL13 levels.

[Transplant-associated lymphoproliferation]. / Transplantations-assoziierte Lymphoproliferationen.

Transplantation of solid organs and haematopoietic stem cells requires immunosuppressive drug therapy in order to prevent rejection or graft-versus-host disease. Depending on dosage and type of drug, the risk of developing an Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is increased. The lesion spectrum ranges from hyperplastic lesions to manifest lymphomas, the latter being classified as monomorphic PTLD. Hyperplastic changes, which are not distinguishable from viral reactions, comprise early or mononucleosis-like lesions. Those with effaced lymph node architecture or extranodal manifestation without a lymphoma-like phenotype are designated polymorphic PTLD. Monomorphic PTLD are either high grade B cell lymphomas, plasma cell neoplasms or Hodgkin lymphomas and only very rarely T cell lymphomas. Low grade B cell lymphomas do not occur. In a subfraction of cases, including even monomorphic PTLD, reduction of immunosuppression alone is sufficient to induce remission of the pathological process.