Disseminated fusariosis in immunocompromised children: a case series and review of literature.

In the era of antifungal prophylaxis for cancer patients, Fusarium genus has become the second leading cause of invasive fungal infections and mortality in this group of patients. The intrinsic resistance to antifungal agents and the patient's risk factors are the most important variables for prognosis and survival. Currently, the use of monotherapy in comparison to combined antifungal treatment information is scarce. In this report, we present a series of three cases of children with acute lymphoblastic leukemia and disseminated fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG). Furthermore, we present a current literature review focused on treatment using monotherapy or combined antifungal treatment.

CD56-Negative Aggressive NK Cell Leukemia Relapsing as Multiple Cranial Nerve Palsies: Case Report and Literature Review.

BACKGROUND: Aggressive natural killer cell leukemia (ANKL) is extremely rare and habitually manifests as a systemic disease with multiorgan failure that rapidly evolves to death. The neoplastic natural killer (NK) cells usually harbor the Epstein-Barr virus (EBV) with a latent viral infection pattern type II; they often have a cytoplasmic CD3ε+ and surface CD3-, CD2+, and CD56+ immunophenotype, and they show complex genetic abnormalities affecting multiple tumor suppressor genes and oncogenes. We present a rare case of CD56-negative ANKL and review the clinical and laboratorial criteria for the diagnosis, as well as the available therapies. CASE PRESENTATION: A European 36-year-old male presented with acute onset fever, pallor, weakness, and jaundice. He had hepatosplenomegaly, severe pancytopenia, hepatic cytolysis, and very high serum lactic dehydrogenase levels. The bone marrow studies resulted in the diagnosis of an EBV-positive, CD56-negative ANKL. The patient failed to respond to gemcitabine and cisplatin-based polychemotherapy, dying three months later with leukemic meningitis and multiple cranial nerves palsies. CONCLUSIONS: The diagnosis of ANKL is difficult and requires both clinical suspicion and an extensive laboratorial approach. Absence of CD56 expression on the neoplastic NK cells may impose difficulties in the diagnosis, which requires morphological, immunophenotypic, histopathological, immunohistochemical, cytogenetic, and molecular studies.

Comparison of Utilization and Clinical Outcomes for Belatacept- and Tacrolimus-Based Immunosuppression in Renal Transplant Recipients.

The performance of belatacept in a real clinical setting has not been reported. A retrospective cohort study was conducted using registry data comparing 1-year clinical outcomes between belatacept- and tacrolimus-treated adult kidney transplant recipients (KTRs) from January 6, 2011, through January 12, 2014. Of 50 244 total patients, 417 received belatacept plus tacrolimus, 458 received belatacept alone, and 49 369 received tacrolimus alone at discharge. In the overall study cohort, belatacept alone was associated with a higher risk of 1-year acute rejection, with the highest rates associated with non-lymphocyte-depleting induction (adjusted hazard ratio 2.65, 95% confidence interval 1.90-3.70, p < 0.0001). There was no significant difference in rejection rates between belatacept plus tacrolimus and tacrolimus alone. In KTRs who met inclusion criteria for the Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial-Extended Criteria Donors (BENEFIT-EXT), 1-year kidney function was higher with belatacept plus tacrolimus and belatacept alone versus tacrolimus alone (mean estimated GFR 65.6, 60.4 and 54.3 mL/min per 1.73 m2 , respectively; p < 0.001). The incidence of new-onset diabetes after transplantation was significantly lower with belatacept plus tacrolimus and belatacept alone versus tacrolimus alone (1.7%, 2.2%, and 3.8%, respectively; p = 0.01). Despite improved graft function and metabolic complications with belatacept alone, it may be advisable to add short-term tacrolimus in the first year after transplant and to consider lymphocyte-depleting induction in patients with high rejection risk, as the risk-benefit ratio allows.

Impact of moisture on survival of Aedes aegypti eggs and ovicidal activity of Metarhizium anisopliae under laboratory conditions.

The effect of relative humidity (43%, 75%, 86% and > 98%) on Aedes aegypti eggs treated with Metarhizium anisopliae or water only was tested for up to a six months exposure at 25 degrees C. Survival of larvae inside eggs was clearly affected by the lowest humidity (43%) tested, and eclosion diminished at all humidities after increasing periods of exposure. M. anisopliae showed to have a strong ovicidal activity only at humidity close to saturation. No difference of activity was found between conidia and hyphal bodies tested. This fungus affected larvae inside eggs and has potential as a control agent of this important vector in breeding sites with high moisture.

Impact of moisture on survival of Aedes aegypti eggs and ovicidal activity of Metarhizium anisopliae under laboratory conditions

The effect of relative humidity (43 percent, 75 percent, 86 percent and > 98 percent) on Aedes aegypti eggs treated with Metarhizium anisopliae or water only was tested for up to a six months exposure at 25ºC. Survival of larvae inside eggs was clearly affected by the lowest humidity (43 percent) tested, and eclosion diminished at all humidities after increasing periods of exposure. M. anisopliae showed to have a strong ovicidal activity only at humidity close to saturation. No difference of activity was found between conidia and hyphal bodies tested. This fungus affected larvae inside eggs and has potential as a control agent of this important vector in breeding sites with high moisture.

Ovicidal activity of entomopathogenic hyphomycetes on Aedes aegypti (Diptera: Culicidae) under laboratory conditions.

The ovicidal activity of 21 hyphomycete fungi species against Aedes aegypti (L.) (Diptera: Culicidae) was tested. Fungi with ovicidal activity developed on high numbers of eggs (> or =70%) during 25 d of exposure. A clear ovicidal activity with low values of hatch (1.3-40%) was observed after 25 d of incubation with Isaria farinosa (Holm: Fries) Fries, Paecilomyces carneus (Duché & Heim) Brown & Smith, Paecilomyces marquandii (Massee) Hughes, Isaria fumosorosea (Wize), Metarhizium anisopliae (Metschnikoff) Sorokin, Penicillium sp., Paecilomyces lilacinus (Thom) Samson, Beauveria bassiana (Balsamo) Vuillemin, and Evlachovaea kintrischica Borisov & Tarasov. More than 63% of eggs hatched after 25-d exposures to 11 other fungi species deemed as ineffective. These are the first results to show the effects of entomopathogenic fungi against eggs of Ae. aegypti, and they suggest their potential as control agents of this vector.

Reactive phenotypes after acute and chronic NK-cell activation.

Several phenotypic changes have been shown to occur after NK-cell stimulation, involving molecules that have been proved to regulate NK-cell migration into tissues and NK-cell activation and proliferation as well as target cell recognition and killing. Here, we review the reactive phenotypes observed in vivo after acute and chronic NK-cell activation.

Immunophenotypic analysis of the TCR-Vbeta repertoire in 98 persistent expansions of CD3(+)/TCR-alphabeta(+) large granular lymphocytes: utility in assessing clonality and insights into the pathogenesis of the disease.

At present, a major challenge in the initial diagnosis of leukemia of large granular lymphocytes (LGLs) is to establish the clonal nature of the expanded population. In the present study we have analyzed by flow cytometry immunophenotyping the TCR-Vbeta repertoire of 98 consecutive cases of persistent expansions of CD4(+) or CD8(+bright) CD3(+)/TCR-alphabeta(+) LGLs and compared the results with those obtained in molecular studies of TCR-beta gene rearrangements. Fifty-eight cases were considered to be monoclonal in molecular studies whereas in the remaining 40 cases there was no evidence for monoclonality (11 cases were considered oligoclonal and 29 polyclonal). The TCR-Vbeta repertoire was biased to the preferential use of one or more TCR-Vbeta families in 96% of cases, a total of 124 TCR-Vbeta expansions being diagnosed: one TCR-Vbeta expansion in 71 cases and two or more TCR-Vbeta expansions in 23 cases. The highest TCR-Vbeta expansion observed in each case was higher among monoclonal (74 +/- 19%) as compared to nonmonoclonal cases (24 +/- 14%) (P = 0.001), as did the fraction of LGLs that exhibited a TCR-Vbeta-restricted pattern (86 +/- 16% and 42 +/- 23%, respectively; P = 0.0001); by contrast, the proportion of cases displaying more than one TCR-Vbeta expansion was higher in the latter group: 7% versus 48%, respectively (P = 0.001). Results obtained in oligoclonal cases were intermediate between those obtained in polyclonal and monoclonal cases and similar results were observed for CD4(+) as for CD8(+bright) T-cell expansions. TCR-Vbeta families expressed in CD8(+bright) T-cell-LGL proliferations showed a pattern of distribution that mimics the frequency at which the individual TCR-Vbeta families are represented in normal peripheral blood T cells. Assuming that a given proliferation of LGLs is monoclonal whenever there is an expansion of a given TCR-Vbeta family of at least 40% of the total CD4(+) or CD8(+bright) T-cell compartment, we were able to predict clonality with a sensitivity of 93% and a specificity of 80%. By increasing the cut-off value to 60%, sensitivity and specificity were of 81% and 100%. In summary, our results suggest that flow cytometry immunophenotypic analysis of the TCR-Vbeta repertoire is a powerful screening tool for the assessment of T-cell clonality in persistent expansions of TCR-alphabeta(+) LGLs.

Immunophenotypic characterization of normal blood CD56+lo versus CD56+hi NK-cell subsets and its impact on the understanding of their tissue distribution and functional properties.

In the present study we have compared the immunophenotypic characteristics of the CD56+lo and CD56+hi NK-cell subsets in a group of normal healthy adults. Our results show that CD56+hi NK-cells display greater light-scatter properties than CD56+lo NK-cells at the same time they have higher levels of CD25 and CD122 IL-2 chains, together with a higher reactivity for HLA-DR and CD45RO and lower levels of CD45RA, supporting that, as opposed to the majority of the CD56+lo population, CD56+hi NK-cells might correspond to a subset of activated circulating NK-lymphocytes. Higher expression of the CD2 and CD7 costimulatory molecules found for the CD56+hi NK-cells would support their greater ability to respond to various stimuli. In addition, CD56+hi NK-cells expressed higher levels of several adhesion molecules such as CD2, CD11c, CD44, CD56, and CD62L compared to CD56+lo NK-cells, supporting a particular ability of these cells to migrate from blood to tissues and/or a potential advantage to form conjugates with target cells. Interestingly, CD56+lo and CD56+hi NK-cells showed a different pattern of expression of killer receptors that might determine different activation requirements for each of these NK-cell subsets. For instance, absence or low levels of CD16 expression might explain the lower antibody-dependent cytotoxicity activity of CD56+hi NK-cells. On the other hand, the virtual absence of expression of the CD158a and NKB1 immunoglobulin-like and the greater reactivity for the CD94 lectin-like killer receptors on CD56+hi in comparison to CD56+lo NK-cells might determine different MHC-class I specificities for both NK-cell subsets, a possibility that deserves further studies to be confirmed.

Association of CD4+/CD56+/CD57+/CD8+(dim) large granular lymphocytic leukemia, splenic B-cell lymphoma with circulating villous lymphocytes, and idiopathic erythrocytosis.

In this paper we report a rare association of a splenic marginal zone B-cell lymphoma with villous lymphocytes and a T-cell large granular lymphocytic leukemia coexpressing CD4 and CD8 as well as CD56 and CD57 natural killer-associated markers in an asymptomatic patient investigated because of an occasional finding of erythrocytosis and leukocytosis in routine blood analysis. We also discuss the possible reasons for this particular association.

Aggressive natural-killer cell lymphoma presenting with skin lesions, breast nodule, suprarenal masses and life-threatening pericardial and pleural effusions.

We report the clinical and laboratory findings of a patient with an aggressive Epstein-Barr virus positive CD2+/CD56+ natural killer-cell lymphoma with a high mitotic activity and complex chromosomal abnormalities presenting with life-threatening pericardial and pleural effusions, disseminated skin lesions, breast nodule and large suprarenal masses. The clinical course was characterized by resistance to chemotherapy and relapsing pericardial and pleural effusions with respiratory and haemodynamic failure. Death occurred 4 months after the first manifestations of the disease as a consequence of cardiac tamponade.

Immunophenotypic aberrations, DNA content, and cell cycle analysis of plasma cells in patients with myeloma and monoclonal gammopathies.

We describe the immunophenotypic and gross DNA defects in 55 patients with myeloma and 50 patients with monoclonal gammopathy and review the literature on this subject (MedLine, 1994-2000). Our data confirmed previous reports indicating that in myeloma nearly all marrow plasma cells are abnormal (98.7 +/- 8.1%). In monoclonal gammopathy the fraction of abnormal plasma cells was 35.0 +/- 32.8%. In both myeloma and monoclonal gammopathy, the most frequent aberrant phenotypic features consisted of absence of expression of CD19, strong expression of CD56, and decreased intensity of expression of CD38; aberrant expression of CD10, CD20, CD22, or CD28 was observed in less than one-third of myeloma cases. The vast majority of cases had two or more phenotypic aberrations. In the DNA studies, 7% of myeloma cases were biclonal and 93% of cases were monoclonal. In those studies with only one plasma cell mitotic cycle, 37% had normal DNA content and 63% were aneuploid (hyperploid, 61%; hypoploid, 2%). The mean percentages of plasma cells in S- and G2M phases were 4.9 +/- 8.5 and 4.4 +/- 6.9%, respectively. Thirty-eight percent of cases had more than 3% of plasma cells in S phase. In monoclonal gammopathy, the DNA index of abnormal plasma cells ranged from 0.89 to 1.30 and the percentage of diploid (31%) and aneuploid (69%) cases was not different from the results found in myeloma. The differences in percentage of abnormal plasma cells in S- (7.4 +/- 8.6%) and G2M-phases (2.4 +/- 1.7%) in patients with monoclonal gammopathy were not statistically significant.

BCL-2 oncoprotein (p26) in splenic lymphoma with villous lymphocytes: a comparative study with other chronic B-cell disorders.

We compared the expression of the BCL-2 oncoprotein (p26) on B cells from 24 patients with splenic lymphoma with circulating villous lymphocytes (SLVL) with that observed on normal, mature B lymphocytes and on neoplastic B cells from 91 patients with other chronic B-cell malignancies. SLVL B cells showed levels of p26 intermediate between those found on normal B lymphocytes and on neoplastic B cells from patients with other chronic B-cell lymphoproliferative disorders.

Decreased expression of bcl-2 (p26) in CD8(+) lymphocytes of patients with T-cell lymphoproliferative disorders of large granular lymphocytes.

The bcl-2 oncogene has been involved in the genesis of various B-cell neoplasms by means of encoding for p26, an apoptosis suppressor oncoprotein. The expression of p26 in lymphoproliferative disorders of large granular lymphocytes (LDLGL), a group of diseases whose mechanism leading to lymphocyte expansion is not yet clear, was not previously characterized. In order to further understand the biology of LDLGL, we compared the expression of p26 in CD8(+) lymphocytes of patients with CD3(+) LDLGL with that observed in normal individuals, patients with viral infection and patients with CD4(+) lymphoid neoplasms. We observed that upregulation of bcl-2 expression is not involved in the genesis of lymphocyte expansion in CD3(+) LDLGL. By contrast, when compared to normal peripheral blood counterparts, CD8(+, bright) lymphocytes of patients with LDLGL express low levels of p26 whereas CD8(+, dim) lymphocytes express normal or only slightly reduced levels of this oncoprotein. A similar pattern of expression of p26 was found in situations in which CD8(+) lymphocytes represent reactive activated cells.

[A comparative study between natural and artificial xenodiagnosis in chronic Chagas' disease patients]. / Estudo comparativo entre o xenodiagnóstico natural e o artificial, em chagásicos crônicos.

In order to study the sensitivity of the xenodiagnosis technique a comparison between natural and artificial xenodiagnosis methods was performed in 57 chronic phase chagasic patients (31 female), with ages ranging from 26 to 83 years. All patients had demonstrable antibodies against Trypanosoma cruzi. Forty first instar nymphs of Dipetalogaster maximus were used for each of both methods and for each patient. The positivity of xenodiagnosis artificial was significantly higher than the routine test method. These results did show that a single application of 40 bugs by the artificial method yielded a similar result than 3 applications of 40 bugs each, by the natural method. The positivity of xenodiagnosis was significantly higher in patients between 56-65 and 66-83 years old than at other ages. Males were predominant in this age group. These results showed the viability of artificial xenodiagnosis and its use in routine laboratory testing.