Is elevation of the serum β-d-glucan level a paradoxical sign for Trichosporon fungemia in patients with hematologic disorders?

SummaryThe detection of serum 1,3-β-d-glucan (BDG) has been reported to be useful for the diagnosis and therapeutic monitoring of various invasive fungal infections. Although Trichosporon fungemia is increasingly recognized as a fatal mycosis in immunocompromised patients, the utility of this assay for Trichosporon fungemia is still unknown. In our experience (28 cases), the level of BDG rose in about half of the patients with hematologic disorders who developed Trichosporon fungemia. Among them, early death from this infection was more frequently seen in BDG-negative patients than in BDG-positive patients. In addition, overall survival was also significantly worse in BDG-negative patients than in BDG-positive patients. There were no significant differences between these two patient groups in terms of clinical background. Unlike for other invasive fungal infections, elevation of BDG level may indicate a paradoxical sign for Trichosporon fungemia in patients with hematologic disorders

Prognostic Relevance of Cytokine Receptor Expression in Acute Myeloid Leukemia: Interleukin-2 Receptor α-Chain (CD25) Expression Predicts a Poor Prognosis.

A variety of cytokine/cytokine receptor systems affect the biological behavior of acute leukemia cells. However, little is known about the clinical relevance of cytokine receptor expression in acute myeloid leukemia (AML). We quantitatively examined the expression of interleukin-2 receptor α-chain (IL-2Rα, also known as CD25), IL-2Rβ, IL-3Rα, IL-4Rα, IL-5Rα, IL-6Rα, IL-7Rα, the common β-chain (βc), γc, granulocyte-macrophage colony-stimulating factor (GM-CSF)Rα, G-CSFR, c-fms, c-mpl, c-kit, FLT3, and GP130 in leukemia cells from 767 adult patients with AML by flow cytometry and determined their prevalence and clinical significance. All cytokine receptors examined were expressed at varying levels, whereas the levels of IL-3Rα, GM-CSFRα, IL-2Rα, γc, c-kit, and G-CSFR exhibited a wide spectrum of ≥10,000 sites/cell. In terms of their French-American-British classification types, GM-CSFRα and c-fms were preferentially expressed in M4/M5 patients, G-CSF in M3 patients, and IL-2Rα in non-M3 patients. Elevated levels of IL-3Rα, GM-CSFRα, and IL-2Rα correlated with leukocytosis. In patients ≤60 years old, higher levels of these 3 receptors correlated with poor responses to conventional chemotherapy, but only IL-2Rα was associated with a shorter overall survival. By incorporating IL-2Rα status into cytogenetic risk stratification, we could sort out a significantly adverse-risk cohort from the cytogenetically intermediate-risk group. Analyses with various phenotypical risk markers revealed the expression of IL-2Rα as an independent prognostic indicator in patients with intermediate-risk cytogenetics. These findings were not observed in patients >60 years old. Our results indicate that several cytokine receptors were associated with certain cellular and clinical features, but IL-2Rα alone had prognostic value that provides an additional marker to improve current risk evaluation in AML patients ≤60 years old

Relationship between IL-2Rα expression levels and OS.

<p>Kaplan—Meier estimates of OS for non-M3 patients ≤60 years old are shown according to the expression levels of IL-2Rα (sites/cell).</p

Double immunostaining of leukemia cells using anti-IL-2Rα and anti-CD13 antibodies in a representative patient with IL-2Rα⁺CD4⁺AML.

<p>The horizontal axis indicates the logarithmic scale of FITC-conjugated anti- IL-2Rα binding, and the vertical axis PE-conjugated anti-CD13 binding. IL-2Rα and CD13 dual-positive cells are shown in the right upper quadrant (B).</p

Correlation of cytokine receptor level with clinicalclinical and cellular features in patients with AML.

<p>Data are given as the mean levels of cytokine receptor expression (sites/cell) ± standard error (number of patients analyzed).</p><p>* <i>p</i> < 0.05.</p><p>**<i>p</i> < 0.01.</p><p>Correlation of cytokine receptor level with clinicalclinical and cellular features in patients with AML.</p

Effect of IL-2Rα expression on cytogenetic-risk classification.

<p>Kaplan—Meier estimates of OS for AML patients ≤60 years old are shown based on the 3 distinct cytogenetic-risk groups. (A) The intermediate-risk group was clearly divided into IL-2Rα⁺ patients and IL-2Rα⁻ patients. (B) Revised survival curves show that the original favorable-risk group, the intermediate-risk group in which IL-2Rα⁺ patients were excluded, and the adverse-risk group in which IL-2Rα⁺ patients in the intermediate-risk group were included.</p