Ihsan Karadogan

Tuberculosis-associated haemophagocytic syndrome: a report of two cases and a review of the literature.

The haemophagocytic syndrome (HS) is an uncommon reactive proliferation of mature histiocytes, and is more frequently but not exclusively associated with infections in individuals with pre-existing immunologic abnormalities. As far as we know, only 13 cases of tuberculosis-associated HS have previously been reported. We present here two cases of disseminated tuberculosis-associated HS. Both of the cases recovered with antituberculosis therapy. High-dose methylprednisolone and intravenous immunoglobulin were added in one case because of the extremely severe clinical presentation. This therapy seemed to contribute to the favourable outcome of the patient. The similarities in HLA phenotypes of this patient and others reported in the literature may provide evidence for an underlying immune dysregulation in some cases of infection-associated HS.

Array comparative genomic hybridization analysis of adult acute leukemia patients.

We have performed a retrospective array-based comparative hybridization (array-CGH) study on 41 acute leukemia samples [n=17 acute lymphoblastic leukemia (ALL) patients only at diagnosis, n=3 ALL patients both at diagnosis and relapse; n=20 acute myeloid leukemia (AML) patients only at diagnosis and n=1 AML patient both at diagnosis and relapse] using an Agilent 44K array. In addition to previously detected cytogenetic aberrations, we observed cryptic aberrations in 95% of ALL and 90.5% of AML cases. ALL-specific recurrent abnormalities were RB1 (n=3), PAX5 (n=4), and CDKN2B (n=3) deletions; AML-specific recurrent abnormalities were HOXA9 and HOXA10 (n=2) deletions and NOTCH1 duplication (n=2). Recurrent duplication of the ELK1 oncogene was observed in both ALL (n=2) and AML (n=3) cases. Our results demonstrate that oligo-array CGH (oaCGH) is an effective method for defining copy number alterations and identification of novel recurring unbalanced abnormalities. At least for now, however, the use of oaCGH for routine diagnosis still has some restrictions.

Peritoneal macrophages function modulation by L-carnitine in aging rats

Background and aims: The aging process is associated with a progressive decline in physiological functions involving immune response in most species. The aim of the present study was to determine the effect of L-carnitine on impaired macrophages function in aged rats. Methods: Superoxide anion production, chemotaxis and phagocytic activity were studied in peritoneal macrophages obtained from young (2 months old) and aged (24 months old) rats. L-carnitine (50 mg/kg bw) or control vehicle was orally gavaged into young and aged rats for 30 consecutive days. Results: The peritoneal macrophages of the aged rats exhibited an increase in superoxide anion generation and a decline in chemotaxis and phagocytic index by comparison with the young rats. Superoxide anion production in aged rats was significantly reduced by L-carnitine treatment, as accompanied by a significant enhancement of chemotactic activity, which was restored to control levels observed in young rats. The age-related reduction in phagocytic index was only slightly, but not significantly, restored by L-carnitine administration, however. Conclusion: The findings suggest that L-carnitine administration may be useful in reversing some age-related changes.

Effects of l-carnitine on neutrophil functions in aged rats

Several age-related alterations occur at the cellular level in the immune system leading to a decrease in the immune response. The present study was designed to determine the effect of L-carnitine on impaired neutrophil functions of aged rats. For this reason, superoxide anion radical production, chemotaxis and phagocytic activity were studied in the neutrophils obtained from the peripheral blood of young and old rats. We orally gavaged L-carnitine (50 mg/kg b.w. per day) or control vehicle into young (2 months) and aged (24 months) rats for 30 consecutive days. The neutrophils of aged rats exhibited an increase in superoxide anion production and decline in phagocytosis and chemotaxis when compared with that in young rat neutrophils. Superoxide anion production in aged rats was significantly decreased by L-carnitine treatment which was accompanied with a significant enhancement of chemotactic and phagocytic activity being restored to control levels. These findings demonstrated that L-carnitine is capable of restoring the age-related changes of neutrophil functions.

Transferrin receptor in proliferation of T lymphocytes in infants with iron deficiency

The aim of this study was to contribute to clarify the mechanism of cellular immune insufficiency occurring during iron deficiency. We studied the expression of the transferrin receptor (TfR) which is called as CD71, on the surface of T lymphocytes in infants with iron deficiency (with and without anemia). A total of 33 infants, aged between 7 and 26 months were included in this study. These subjects were divided into three groups: (i) latent iron deficiency (LID) (group 1), (ii) iron deficiency anemia (IDA) (group 2), and (iii) healthy infants (group 3). Both CD3 levels and CD71 expression of T lymphocytes were analysed by flow cytometry before and after phytohaemagglutinin (PHA) stimulation. The percentage of CD3+ lymphocytes in infants with IDA was lower than that in controls after PHA stimulation (mean ± SD, 48.6 ±10.5%vs. 70.7 ±7.8%, P < 0.001). The TfR expression of T lymphocytes (CD3 + CD71%) increased in all three groups after PHA stimulation (P < 0.001). No significant difference was seen among the three groups with respect to CD3 + CD71%. Although there was a reduction in the proliferative capacity of T lymphocytes in infants with IDA, their ability to express transferrin receptor on T‐lymphocyte cell surface was normal.

rHuG-CSF increases the platelet-neutrophil complex formation and neutrophil adhesion molecule expression in volunteer granulocyte and stem cell apheresis donors.

Abstract:  Several reports have shown that granulocyte colony‐stimulating factor (G‐CSF) administration induces a transient, mild hypercoagulable state, which might predispose certain donors to thrombotic complications. In the present study, changes in the expression of neutrophil adhesion molecules (CD11b/CD18, CD62L) and platelet‐neutrophil complex formation following rHuG‐CSF administration were investigated in normal granulocyte and stem cell donors. For granulocyte apheresis (N = 10), rHuG‐CSF (5 µg/kg) was given subcutaneously every 12 h three times and apheresis was carried out two hours after the last dose. For stem cell apheresis (N = 8), rHuG‐CSF (10 µg/kg/day) was given subcutaneously for 5 days and apheresis was carried out when peripheral CD34+ cell counts exceeded 20 cell/µL. Expression of neutrophil adhesion molecules (CD11b/CD18, CD62L) and platelet‐neutrophil complex formation following rHuG‐CSF administration were investigated in donors by a flow cytometric method. A significant increase in neutrophil counts (P < 0.001), and decreases in platelet counts (P < 0.01) and hemoglobin levels (P < 0.01) occurred following G‐CSF administration. The expression of CD11b/CD18 significantly increased (P < 0.001) over pretreatment values with G‐CSF administration and returned to baseline 1 week after stopping the drug. In contrast, CD62L expression was decreased (P < 0.01) with G‐CSF and returned to normal after cessation of the drug. rHuG‐CSF caused more than a two‐fold increase (from 0.3 to 7.0 × 109/L) in circulating platelet‐neutrophil complexes (P < 0.01), which returned to normal after 1 week. Although clinical significance of these laboratory changes is not clear, the occurrence of neutrophil activation and increased platelet‐neutrophil complex formation might predispose certain donors or patients to thrombotic complications following G‐CSF administration.

Myelodysplastic Syndrome in a Patient with Werner’s Syndrome

Werners syndrome is a relatively rare autosomal recessive disorder characterized by several features generally associated with aging. This syndrome is classified in the group of chromosome instability syndromes and there is an increased incidence of neoplasia. Hematologic malignancies associated with this syndrome are, however, unusual. Herein we report a case of Werners syndrome with myelodysplastic syndrome, a clonal preleukemic disorder of hemopoietic stem cells. Such an association, to the best of our knowledge, has not been reported in the English literature so far.

Recommendations for Risk Categorization and Prophylaxis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Expert Opinion (TEO-4)

This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease.

Aberrations of Chromosomes 9 and 22 in Acute Lymphoblastic Leukemia Cases Detected by ES-Fluorescence In Situ Hybridization

A reciprocal translocation between chromosomes 9 and 22 creates oncogenic BCR/ABL fusion in the breakpoint region of the derivative chromosome 22. The aim of this study was to evaluate the importance of atypical fluorescence in situ hybridization (FISH) signal patterns in pediatric and adult acute lymphoblastic leukemia (ALL) cases. We evaluated t(9;22) translocation in 208 cases with ALL (294 tests), including 139 childhood and 69 adult cases by FISH technique using BCR/ABL extra signal (ES) probe. FISH signal patterns observed in pediatric ALL cases were as follows; Major-BCR/ABL (M-BCR/ABL) (1.4%), minor-BCR/ABL (m-BCR/ABL) (3.6%), trisomy 9 (4.3%), trisomy 22 (4.3%), trisomy or tetrasomy of both chromosomes 9 and 22 (2.9%), monosomy 9 (1.4%), monosomy 22 (0.7%), ABL gene amplification (1.4%), derivative chromosome 9 deletion (1.4%), and extra copies of the Philadelphia chromosome (1.4%). FISH signal patterns observed in adult ALL cases were as follows; M-BCR/ABL (5.8%), m-BCR/ABL (11.6%), two different cell clones with major and minor BCR/ABL signal pattern (2.9%), extra copies of Philadelphia chromosome (4.3%), derivative chromosome 9 deletion (1.4%), trisomy 9 (2.9%), tetraploidy (1.4%), monosomy 9 (1.4%), trisomy 22 (1.4%), and coexistence of both trisomy 22 and monosomy 9 (1.4%). Trisomy 9, trisomy 22, and polyploidy of chromosomes 9 and 22 were specific atypical FISH signal patterns for childhood B cell acute lymphoblastic leukemia (B-ALL) patients. However, monosomy 9 and ABL gene amplification were highly specific for childhood T cell acute lymphoblastic leukemia (T-ALL) patients. Our report presents the correlation between atypical FISH signal patterns and clinical findings of a large group of ALL cases.