BK-virus-associated hemorrhagic cystitis in children after hematopoietic stem cell transplantation.

BACKGROUND: BK-virus-induced hemorrhagic cystitis (BK-HC) is a serious complication in children undergoing hematopoietic stem cell transplantation (HSCT). Data of BK-HC in children undergoing HSCT are still limited. AIM OF THE STUDY: To describe the epidemiology, clinical course, and outcome of children with BK-HC after HSCT. MATERIALS AND METHODS: The medical records of all children aged 0 to 20 years, who underwent HSCT at Schneider Children's Medical Center between 2000 and 2008 and were diagnosed with BK-HC, were reviewed for demographic, clinical, and microbiological data. Patients in whom BK-HC had developed were compared with patients in whom it did not. RESULTS: Seventeen children (5.3%) acquired BK-HC at 10 to 180 days after HSCT (mean, 57 d); 9 had grade 3 to 4 disease. Bleeding lasted for 4 to 42 days (mean, 14). All patients but 1, who died of unrelated causes, recovered. Follow-up ranged from 6 to 91 months (mean, 35 months). Acute myeloid leukemia, use of cyclophosphamide in the conditioning regimen, unrelated donor, and older age were associated with the development of hemorrhagic cystitis (HC). CONCLUSIONS: The incidence of BK-HC in children after HSCT is relatively low. Its rate of successful resolution is very high. Further prospective studies are required to determine optimal therapy.

Characterization of adhesion and viability of early seeding hematopoietic cells in the host bone marrow in vivo and in situ.

OBJECTIVE: Homing and seeding are essential early events of engraftment that depend on the interaction of hematopoietic cells with the host bone marrow (BM) stroma. We used optical techniques to characterize the adhesion patterns and viability of bone marrow cells (BMC) at the level of recipient BM microenvironment. MATERIALS AND METHODS: Donor cells labeled with PKH dyes were tracked in vivo through an optical window placed over the femoral epiphysis of nonconditioned recipients. Adhesion to BM stroma was assessed with laser tweezers, and viability was assayed by fluorescence resonance energy transfer of the pair PKH67-propidium iodide (PI) in freshly excised femurs. RESULTS: Three hours after intravenous injection, an estimated 30% of the labeled cells in the femur were immobile. The percent of adherent cells increased to 74+/-3% and 97+/-2% on days +1 and +3, respectively, (p<0.001), and similar fractions of cells were viable at these times (p<0.001). The observation that all adherent cells were viable suggested a correlation between these parameters. The day +3 BM-seeded cells rescued secondary myeloablated allogeneic hosts. Seeding in the host BM was accompanied by (4.5-fold) enrichment of cells expressing SCA-1 and was 22-fold higher for lineage-negative Lin(-) cells compared to lineage-positive cells (p<0.001). Pretreatment of Lin(-) cells with anti-VLA-4 antibodies caused a 2.4-fold decrease in homing and a 4.6-fold decrease in seeding (p<0.001). CONCLUSIONS: The data indicate that adhesion is rate-limiting determinant of homing and early seeding, and a crucial event that preserves the viability of cells toward successful engraftment. The role of VLA-4 is more important for primary seeding than it is for homing to the BM.

The topologic and chronologic patterns of hematopoietic cell seeding in host femoral bone marrow after transplantation.

The early stages of homing, seeding, and engraftment of hematopoietic stem and progenitor cells are poorly characterized. We have developed an optical technique that allows in vivo tracking of transplanted, fluorescent-tagged cells in the host femurs. In this study we used fluorescence microscopy to monitor the topologic and chronologic patterns of hematopoietic cell seeding in the femoral bone marrow (BM) of mice. PKH-labeled cells homed to the femur within minutes after injection into a peripheral vein. Most cells drifted within the marrow space and gradually seeded in clusters close to the endosteal surface of the epiphyseal cortex. Three days after transplantation 85% to 94% (14%) of PKH-labeled cells in the femoral marrow were located within 100 microm of the epiphyseal bone surface (P <.001 versus the more central cells), whereas labeled cells were absent in the femoral diaphysis. Primary seeding of juxtaendosteal, epiphyseal marrow occurred independently of recipient conditioning (myeloablated and nonconditioned hosts), donor-recipient antigen disparity, or the phenotype of the injected cells (whole BM and lineage-negative cells) and was consistently observed in secondary recipients of BM-homed cells. Seeding in regions close to the epiphyseal bone was also observed in freshly excised femurs perfused ex vivo and in femurs assessed without prior placement of optical windows, indicating that the site of primary seeding was not affected by surgical placement of optical windows. Four to 5 days after transplantation, cellular clusters appeared in the more central regions of the epiphyses and in the diaphyses. Centrally located cells showed decreased PKH fluorescence, suggesting that they were progeny of the seeding cells, and brightly fluorescent cells (quiescent first-generation seeding cells) were observed close to the bone surface for as long as 24 days after transplantation. These data indicate that the periphery of the femoral marrow hosts primary seeding and that quiescent cells continue to reside in the periphery for weeks and do not divide. The site of proliferation of transplanted cells is the center of the marrow space.

Ecthyma gangrenosum caused by disseminated Exserohilum in a child with leukemia: a case report and review of the literature.

We report an 8-year-old boy with acute leukemia who developed ecthyma gangrenosum secondary to infection with Exserohilum spp., a rare cause of human disease. The skin, paranasal sinuses and lungs were involved. To the best of our knowledge, this is the first report of ecthyma gangrenosum caused by Exserohilum spp. This case emphasizes the importance of prompt skin biopsy for early diagnosis and treatment of this life-threatening infection.