The effect of bone marrow graft composition on pediatric bone marrow transplantation outcomes.

Hematopoietic stem cell graft cellular composition has been generally accepted to impact outcomes. Recent studies question this hypothesis. We conducted a single-center retrospective study of sixty-one pediatric BMT recipients for malignant (68%) and nonmalignant diseases (32%) examining effects of graft composition on engraftment, acute GVHD, chronic GVHD, and survival at day 100 and 1 year. Grafts contained a median of 3.63 x  08 TNC/kg (range: 0.031-10.31 x 108 TNC/kg) and 4.09 x 106 CD34+ /kg (range: 0.76-24.15 x 106 CD34+ /kg) with median neutrophil and platelet engraftment times of 17 and 29 days, respectively. A univariate analysis showed a trend for increasing TNC and increasing time to neutrophil engraftment HR: 0.875; CI: 0.075-1.001). Increasing CD34+ counts shortened time to platelet engraftment (HR: 1.085; CI: 1.015-1.161). No significant relationship was found between TNC, CD34+ , or CD3+ and acute or chronic GVHD. TNC or CD34+ did not affect day 100, 1-year survival, or 2-year survival. Increasing CD3+ counts demonstrated a negative trend on day 100 survival (HR: 1.108; CI: 1.001-1.036) but not 1-year survival or 2-year survival. These results add additional data questioning the effect of graft composition on outcomes in pediatric BMT patients with important ramifications for the management of donors.

Cases of transfusion-transmitted babesiosis occurring in nonendemic areas: a diagnostic dilemma.

BACKGROUND: Transfusion-transmitted babesiosis (TTB) has been rapidly increasing in incidence since the beginning of the 21st century. Asymptomatic individuals with Babesia infection are able to donate blood in the United States because of the lack of specific blood donation testing. Blood products collected in Babesia-endemic areas are distributed nationally; thus, clinicians in nonendemic states may fail to include babesiosis in the differential diagnosis of a patient who had a recent transfusion history and a fever of unknown origin. STUDY DESIGN AND METHODS: We report the details of two cases of clinical transfusion-transmitted babesiosis and one asymptomatic infection identified in red blood cell recipients in two nonendemic states (South Carolina and Maryland), which, when combined with three recent additional cases in nonendemic states, totals six recipient infections in three nonendemic states. RESULTS: Delayed diagnosis of transfusion-transmitted babesiosis places patients at risk for increased morbidity and mortality and may result in clinical mismanagement or unnecessary treatments. A peripheral blood smear should be reviewed in any patient with a recent transfusion and a fever of unknown origin. Prompt communication of the diagnosis among physicians is key to ensuring that patients with transfusion-transmitted babesiosis are treated expeditiously, and a transfusion service investigation is necessary to identify additional recipients from the same donor. CONCLUSION: TTB is appearing in traditionally nonendemic states because of blood product distribution patterns. Clinicians should include TTB on the differential diagnosis in any patient presenting who had a recent transfusion history and a fever of unknown origin, regardless of where the transfusion took place.

Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature.

Vici syndrome is a rare congenital disorder first described in 1988. To date, 31 cases have been reported in the literature. The characteristic features of this syndrome include: agenesis of the corpus callosum, albinism, cardiomyopathy, variable immunodeficiency, cataracts, and myopathy. We report two Hispanic sisters with genetically confirmed Vici syndrome who both developed Idiopathic Thrombocytopenic Purpura. To our knowledge, this is an immunologic process that has been previously undescribed within the phenotype of Vici syndrome and should be added to the spectrum of variable immune dysregulation that can be found in these patients.

Co-occurrence of Langerhans cell histiocytosis and Rosai-Dorfman disease: possible relationship of two histiocytic disorders in rare cases.

Rosai-Dorfman disease and Langerhans cell histiocytosis are both disorders of accessory immune cells. Two cases have been previously reported of concurrent Langerhans cell histiocytosis and Rosai-Dorfman disease. In this report, we characterize the findings and selected molecular studies in nine additional cases. Histology was reviewed. Immunohistochemical stains were performed on all cases in which slides or blocks were available. A combination of CD1a, S-100, CD3, CD20, langerin, CD68, CD163, CD21, CD35 and CD123 immunohistochemical stains were performed. High-resolution array comparative genomic hybridization was performed on six samples from five cases. In these cases, seven were female and two male, with an average age of 25 years (15 months-59 years). A majority of the cases were identified in lymph node. Areas of Langerhans cell histiocytosis had a typical appearance with the existence of bland 'coffee-bean' nuclei, clear cytoplasm and associated eosinophils. The immunophenotype was typical, including expression of CD1a, S100, CD68 and langerin. In areas of Rosai-Dorfman disease, there was emperipolesis seen in all cases. Cells were intermediate-large in size with large round nuclei and ample clear or pale cytoplasm. The lesional cells were positive for S100, CD68, CD163, without expression of langerin or CD1a. Array comparative genomic hybridization showed gains and/or losses in four of the six samples. One case showed no gains or losses and one additional case showed gains and losses in the Langerhans cell histiocytosis, while no abnormalities were discovered in the Rosai-Dorfman disease component. These findings are comparable to those seen in previous studies of Langerhans cell histiocytosis. We report the clinical and pathologic findings of the combination of Langerhans cell histiocytosis and Rosai-Dorfman disease. Furthermore, we suggest on the basis of evidence from our cases that, when simultaneous, the two entities may be pathophysiologically related.

Refractory ascites as a presenting feature of extramedullary plasmacytoma in an end-stage renal disease patient with HIV infection.

Refractory ascites as the only presenting feature of an extramedullary plasmacytoma complicating end-stage renal disease and HIV infection has not been described yet. We describe a case of a 39-year-old female with HIV-associated nephropathy manifesting with ascites formation after transition from peritoneal dialysis (PD) to hemodialysis (HD). Earlier on, she received cycler-assisted PD for 5 years uneventfully. A few weeks after HD transition, a striking refractory ascites developed requiring multiple paracenteses (5 - 7 L every second week). Serum protein electrophoresis showed hypoalbuminemia with only small amount of monoclonal IgG-κ at 0.30 g/dL. Serum immunofixation electrophoresis showed polyclonal immunoglobulins with polyclonal light chains. Both κ and λ light chains were increased, at 66.86 mg/dL (reference range: 0.33 - 1.94) and 18.55 mg/dL (reference range: 0.57 - 2.63), respectively, with a ratio of 3.6 (reference range: 0.26 - 1.65). However, an ascitic fluid analysis showed a marked increase in plasma cells with a κ : λ ratio greater than 5 : 1. Omental biopsy confirmed κ-restricted plasma cells. Multiple myeloma work-up with skeletal survey showed no evidence of focal osseous lesions, while bone marrow aspiration and biopsy also remained unremarkable. Accordingly, the diagnosis of omental extramedullary plasmacytoma with malignant ascites was confirmed. Conversion from PD to HD may unmask an underlying pathology favoring ascites formation.

Bryostatin 1/ionomycin (B/I) ex vivo stimulation preferentially activates L-selectinlow tumor-sensitized lymphocytes.

We have shown that tumor vaccine-sensitized draining lymph node (vDLN) cells activated ex vivo with bryostatin and ionomycin (B/I) were capable of inducing antigen-specific regression of a murine mammary tumor, 4T07. vDLN cells not activated with B/I were ineffective. We hypothesized that B/I selectively activates tumor-sensitized (CD62Llow) lymphocytes, to account for the highly potent and tumor-specific activity. We hypothesized that CD8+ CD62Llow cells may be preferentially activated by B/I treatment, infiltrate the tumors and mediate tumor regression in mice. 4T07-IL2 tumor cells were injected into one hind footpad of BALB/c mice. Ten days later, vDLN were harvested and separated based on CD62L expression. After separation, cells were activated with B/I, expanded with IL2 (40 IU/ml) for 10 days, and adoptively transferred to 4T07 tumor bearing mice. Naive mice were also treated with different subsets of T cells and later were challenged with 4T07 tumor cells. To test in vitro responses to antigen, expanded lymphocytes were cultured either alone or with irradiated 4T07 tumor cells. Supernatants were harvested after 24 h and tested by ELISA for IFN-gamma. The importance of the host immune response was tested by AIT into 4T07-bearing nude athymic mice. Host mice were depleted in vivo of CD4 or CD8 T cells after vDLN AIT to ascertain the mediators of tumor regression. In order to track B/I activated vDLN cells, they were prestained with CFSE prior to adoptive transfer into tumor-bearing hosts. At various time points, tumors, spleens and lymph nodes of host mice were harvested, dual stained for activation marker expression and analyzed by flow cytometry. CD62Llow cells expanded 12-fold more than CD62Lhigh lymphocytes during the 10 day culture period. Supernatant from CD62Llow cells + 4T07 cultures contained 33-fold more IFN-gamma than supernatant from CD62Lhigh cells + 4T07 cultures (843.9 pg/ml +/- 135.8 vs 25.89 pg/ml +/- 0.01). Adoptive transfer of CD62Llow lymphocytes induced complete tumor regressions in all mice, while tumors regressed in only 17% of mice treated with CD62Lhigh lymphocytes. Naive mice that received B/I-activated CD62Llow cells were protected from future tumor challenges, while mice given CD62Lhigh cells did not exhibit the same resistance to tumor growth. Tumors in nude host mice regressed after AIT treatment. In vivo depletion of CD4 T cells after AIT did not inhibit tumor regression, but CD8 T cell depletion abrogated tumor regression. vDLN cells tracked preferentially to tumor draining lymph nodes and proliferated in vivo, persisting for at least 21 days, and were 95% CD44+ and 39% CD69+. Bryostatin 1 and ionomycin, by increasing PKC activity and intracellular calcium, respectively, mimic intracellular signals that result in T cell activation. CD62Llow cells are preferentially activated by B/I, leading to a highly effective anti-tumor T cell population.