Does hand mirror morphology a useful diagnostic tool for the treatment decision of acute undifferentiated leukemia at admission?

Abstract: It is difficult how to manage acute undifferentiated leukemia in daily practice, but generally, hand mirror morphology provides ease to treat these patients. Thirty-nine years old male patient was admitted to with the complaints of echymosis, and pain at his left buttock due to an intramuscular injection for the treatment of previously diagnosed of the lower respiratory infection. Peripheral blood smear revealed >%50 blasts cells with a moderate nuclear: cytoplasmic ratio and one or more nucleoli. The blast cells showed a hand-mirror morphology and not harboring auer rods. According to the flow cytometric analysis the blastic cells do not represent to be originated from myeloid or lymphoid origin, because the cells harboring both of two cell lineages. AML-like therapy was commenced based on the positive myeloid markers including CD117 and CD135. Even though hand mirror morphology of the blasts usually demonstrates the lymphoid origin and the patients are treated as ALL like therapy, myeloid blasts rarely represents the same morphology, as was in our patient.

Posttransplant lymphoproliferative disorders in transplant recipients.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with a reported incidence between 0.8% and 32%. The incidence of PTLD mainly depends on the transplanted organ, the immunosuppressive drugs, the viral serology, and the age of the recipient. The aim of our study was to analyze our patients diagnosed with PTLD. Among 1040 transplantations, including 931 renal, 14 heart, 55 liver and 40 allogeneic peripheral blood stem cell (PBSC), 8 patients (7 male, 1 female) were diagnosed with PTLD. Five patients had undergone renal, one cardiac, one liver, and one PBSC transplantations. Four patients were diagnosed within the first year of transplantation. Six patients presented with abdominal disease, one with convulsions, and one with peripheral lymph node involvement. According to the World Health Organization classification system, six patients were diagnosed as diffuse large B-cell lymphoma, one patient Burkitt's lymphoma, and one polymorphic PTLD. At the time of diagnosis, 7 patients showed positive Epstein-Barr virus (EBV) and cytomegalovirus (CMV) Ig G and negative Ig M; one patient, positive EBV Ig M and negative CMV Ig G and M. EBV viral load was extremely high in the plasma of two patients by polymerase chain reaction. One of these patient's pathologic tissue revealed positive EBV DNA, which was not detected in six of the other eight patients. This patient was an 8-year-old boy diagnosed with Burkitt's lymphoma at 31 months after liver transplantation. Seven patients died of disease or complications of chemotherapy. Only one patient survived after the diagnosis of PTLD. In conclusion, even with treatment the mortality rate was high among our patients with PTLD. To decrease the incidence of PTLD and related mortality, risk factors must be evaluated in multicenter studies.

Sheehan's syndrome associated with pancytopenia due to marrow aplasia; full recovery with hormone replacement therapy.

We describe a 52-year-old woman with pancytopenia associated with Sheehan's syndrome, whose presenting feature was severe malaise and syncope after a psychological stress. Hormonal replacement therapy alone (with L-thyroxine and prednisolone) produced clinical and full haematological recovery. This is a very rare case of Sheehan's syndrome because the diagnosis was delayed for 27 years after delivery, and it was associated with pancytopenia.

Successful Surgical Management of Typhlitis in a Patient with Acute Myeloblastic Leukemia.

Typhlitis (neutropenic enterocolitis) is a potentially life-threatening complication associated with neutropenia and combination chemotherapy. The incidence of this disease is increasing in both patients with hematologic malignancies and solid tumors with the advent of more aggressive chemotherapy. Here, we describe a patient with acute myeloblastic leukemia in whom typhlitis developed during induction chemotherapy and managed successfully with both medical and surgical intervention during neutropenic period. Our experience reinforces prior reports that intense medical treatment, close observation and emergent surgical intervention has been shown to be life saving.

Single automated donor plateletpheresis increases the plasma level of proinflammatory cytokine tumor necrosis factor-alpha which does not associate with endothelial release markers von Willebrand factor and fibronectin.

The effect of plateletpheresis on endothelium, which has strong effects on blood coagulation, fibrinolysis and platelet function, is not known. Activation of leukocytes and subsequent generation of proinflammatory cytokines during the extracorporeal circulation may activate the endothelium. To test this hypothesis we measured plasma levels of tumor necrosis factor (TNF)-alpha as a prototype of the proinflammatory cytokines, and von Willebrand factor (vWF) and fibronectin as endothelial release/damage markers before and after a single plateletpheresis procedure on an intermittent-flow machine Haemonetics MCS 3p in 17 healthy donors. We found a significant increase in median plasma level of TNF-alpha following plateletpheresis (3.5 vs 26.5 pg/ml, P=0.02). Such increases in vWF and fibronectin were not observed. The increase in plasma TNF-alpha indicates that a single plateletpheresis procedure causes leukocyte activation which does not seemingly impair endothelial cell function. The relation of plateletpheresis-induced proinflammatory cytokine release to some adverse effects observed in both donors and recipients, and the effect of repeated plateletpheresis on endothelium deserve further studies.

Hepatitis C virus association with non-Hodgkin's lymphoma.

Infectious etiology has been confirmed only in a few lymphoproliferative disorders such as human T-cell lymphotropic virus in adult T-cell leukemia lymphoma, Epstein-Barr virus in African-type Burkitt's lymphoma and Hodgkin's disease, and Helicobacter pylori infection in primary gastric B-cell lymphoma. In recent years, Ferri and colleagues have found hepatitis C virus (HCV) association with non-Hodgkin's lymphoma (NHL) in Italy. The aim of our study was to determine the HCV association in NHL patients in Antalya. Forty-eight patients (22 women and 26 men, with a median age of 52 years) with NHL were included in the study. The control group consisted of 28 patients with various hematological disorders (11 women and 17 men with a median age of 50 years). Anti-HCV antibodies were investigated in 48 patients, and HCV RNA was assessed in 35 of them. Anti-HCV antibodies were found to be negative in the NHL group, but HCV RNA was positive in the serum of three patients (8.6%), who were diagnosed with diffuse small cell lymphoma (19%). Anti-HCV antibodies and HCV RNA were negative in the control group. Since HCV association with NHL has previously been reported in Italy, it is likely that both genetic and environmental factors in the Mediterranean sea-region may be involved in the oncogenesis in HCV RNA-positive patients. Multicenter studies with large patient groups will disclose the true association of HCV with NHL in Turkey.

Flow cytometric analysis of circadian changes in platelet activation using anti-GMP-140 monoclonal antibody.

The hemostatic activity of blood shows a circadian variation with a higher frequency of acute coronary events in the morning. The thrombotic tendency of blood is influenced by many factors, including platelets. Diurnal changes of in vivo platelet activation were investigated by whole blood flow cytometry in 10 young healthy male volunteers using anti-GMP-140 (anti-alpha-granule membrane protein 140 kD) monoclonal antibody at 3h intervals from 06:00 to 24:00. We also studied circulating platelet aggregates to investigate whether there exists a similarity between the results of these methods. Results of flow cytometric analysis indicate that there is an increase in platelet activation during the period from 06:00 to 09:00. Platelet activation then decreases gradually during the period from noon to midnight. These changes are accompanied by a similar trend in circulating platelet aggregates. This suggests that GMP-140 expression on platelets is synchronized with or followed by platelet aggregate formation in vivo, and increased platelet activation may predispose individuals to thrombosis at this time.

Circadian variations in natural coagulation inhibitors protein C, protein S and antithrombin in healthy men: a possible association with interleukin-6.

Recent observations describe an increase in platelet aggregability and a decrease in fibrinolytic activity in the early morning hours. To determine whether anticoagulant proteins also show such a circadian variation we measured protein C (PC), protein S (PS), antithrombin (AT) and heparin cofactor-II (HC-II) levels on venous plasma samples taken from 10 healthy men at three-hour intervals throughout a 24-hour period. To investigate the possible temporal mapping of circadian periodicity, we also measured plasma levels of beta-thromboglobulin (beta-TG) as an indicator of platelet activation, and interleukin-6 (IL-6) as one of the possible regulatory factors that drive this rhythm. Blood samples were drawn at 6 a.m., 9 a.m., noon, 3 p.m., 6 p.m., 9 p.m. and midnight. PC, IL-6 and beta-TG were measured by ELISA, PS and AT by latex immune assay and HC-II by chromogenic substrate method. A significant circadian variation was found in PC, PS, AT, beta-TG and IL-6, but not in HC-II levels. PC, PS, IL-6 and beta-TG were at their peaks at 6 a.m., and nadirs at a time from noon to midnight. AT peak was at 6 p.m. and nadir at noon. The regression of PS on IL-6 was significant. Although the fluctuations of PS and AT were within the normal ranges during the day, some PC levels of two subjects were below the lower normal limit (0.70). These data indicate that PC, PS, and AT show a marked circadian periodicity as the other components of the blood coagulation and fibrinolytic system do. The similar trends in plasma concentrations of PC, PS, beta-TG and IL-6 may be coincidental, but could reflect a common regulatory mechanism or an effect on each other. The clinical implications of these physiological changes in coagulation inhibitors and the role of IL-6 in the anticoagulant response deserve further studies.

The use of recombinant human G-CSF in the treatment of propylthiouracil-induced agranulocytosis.

A 43-year-old female patient with Basedow-Graves' disease developed agranulocytosis in the eighth month of propylthiouracil therapy. After discontinuing the drug, a broad spectrum antibiotic regimen plus recombinant human granulocyte colony-stimulating factor (G-CSF), a human haematopoietic growth factor, were started. Her granulocyte count returned to normal with the second dose of G-CSF, and ulcerating pharyngitis improved rapidly. We think that in patients with propylthiouracil-induced agranulocytosis, G-CSF will reduce the risk and severity of infection, and should be accepted as a part of the standard therapy.

Increased Serum Soluble CD23 and Soluble IL-2R Levels in Haematologic Malignancies.

Serum soluble CD23 (sCD23) and soluble IL-2 receptor (sIL-2R) levels increase not only in disorders with immune system activation, but also in hematological malignancies. They have been used as markers of disease progression and/or the response to therapy in lymphoproliferative disorders (LPD). In this study, we investigated the serum sCD23 and sIL-2R levels of 21 patients with different hematological malignancies [10 LPD, 6 multiple myeloma (MM), and 5 myelodysplastic syndrome (MDS)] before treatment, and compared them with 19 age- and sex- matched healthy subjects. Median sIL-2R levels were found to be significantly elevated in both the overall patient group and each of the subgroups. Median sCD23 levels were significantly higher in the overall patient group and in patients with LPD and MM. A positive correlation was found between sIL-2R and sCD23 levels in LPD. Our preliminary findings suggest that elevated serum levels of these soluble factors are not only markers of LPD but might be also used for other hematologic malignancies, except for MDS. Further studies should be designed to find out if it might be the result of an overactive immune system or not.

Glycemic control and coagulation inhibitors in diabetic patients.

OBJECTIVE: To investigate the plasma antigenic levels and functional activities of coagulation inhibitors in poorly controlled diabetic patients and the possible effect of good glycemic control on these parameters. RESEARCH DESIGN AND METHODS: Both functional activities and plasma antigenic levels of coagulation inhibitors (antithrombin III, heparin cofactor II, protein C, and protein S) and plasma levels of C4b-binding protein were measured in 28 diabetic patients (13 males, 15 females; 2 IDDM, 26 NIDDM; median age 56.5 years; median duration of diabetes 5.5 years) with poor glycemic control (median HbA(1c) 11.8%). Twenty-three healthy subjects were enrolled as controls. Following a 3-month intensification of antihyperglycemic therapy, good glycemic control (HbA(1c) <8%) was achieved in 17 patients, and the plasma levels of the same parameters during this period were compared with baseline values. RESULTS: Functional activities and plasma antigenic levels of coagulation inhibitors were comparable in poorly controlled diabetic patients and healthy subjects. In patients achieving good control after 3 months, there was a significant reduction in plasma antigenic levels of protein S (p = 0.005) and C4b-binding protein (p = 0.03); however, no difference could be observed in other parameters. HbA(1c) did not show any correlation with plasma antigenic levels or functional activities of coagulation inhibitors either at baseline or at 3 months of good glycemic control. CONCLUSIONS: Our findings suggest that in poorly controlled diabetic patients, coagulation inhibitors are not different from healthy controls. Short-term good glycemic control may not exert a profound effect on coagulation inhibitors except protein S and its binding protein, C4b-binding protein.

Granulocyte and granulocyte-macrophage colony-stimulating factors, their receptors and interleukin-3 levels in newborns.

Serum levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and interleukin-3 (IL-3) as well as neutrophil counts were studied on the first, second and fifth days after birth, in order to elucidate the relations between neutrophil kinetics and these hematopoietic factors. The G-CSF and GM-CSF receptors on neutrophils were also investigated in 16 healthy newborns. G-CSF and GM-CSF receptor-positive neutrophil percentages were not different from those in the peripheral blood of adult controls. The receptor densities, assessed by mean fluorescence channel number, were also similar in newborn and adult neutrophils. The mean serum concentrations of G-CSF were high (191 pg/ml) on the first day of life and gradually decreased on the second (128 pg/ml) and fifth (112 pg/ml) days. A statistically significant correlation (p < 0.05) was found between G-CSF levels and absolute neutrophil counts (ANC). Furthermore, the percentage of decrease in G-CSF levels correlated significantly with the percentage of decrease in ANC (p < 0.001). GM-CSF levels were also high, though less striking, on the first day of life (9.5 pg/ml), remained at high levels on the second (10 pg/ml), and gradually decreased on the fifth (8.8 pg/ml) day. IL-3 levels were high (110 pg/ml) on the first day of life and remained at high levels on the second (138 pg/ml) and fifth (138 pg/ml) days. We found that the IL-3, GM-CSF and G-CSF levels were elevated during the first week of postnatal life. Our findings suggest that significant changes in the levels of the growth factors are likely to be the cause of significant leukocyte blood picture changes during the first week of life. We found normal GM-CSF and G-CSF receptors in uninfected newborns.

Automated plateletpheresis does not cause an increase in platelet activation in volunteer donors.

Activation of platelets during collection and storage has been implicated as a major cause of the platelet storage lesion. In this study, we investigated the effect of an automated plateletpheresis procedure on the in vivo platelet activation in 20 volunteer donors. Peripheral blood samples were collected immediately before and after plateletpheresis on the Haemonetics V50 Blood Cell Separator. Activation of platelets was determined by quantitating the amount of platelet P-selectin (CD62) expression using a whole blood method on flow cytometry. Adenosine diphosphate (ADP), collagen, and ristocetin induced platelet aggregations were also measured on a whole blood impedance aggregometer. Plateletpheresis caused a significant decrease in the CD62-positive platelet percentage and aggregation responses to 3 agonists. We concluded that the plateletpheresis procedure did not cause an increase in platelet activation in donors. Further studies are required to elucidate whether activated platelets are collected during the procedure or removed from the circulation of the donor and replaced by resting platelets, activated platelets bind to leukocytes or endothelial cells, and the plateletpheresis procedure is a powerful stimulus for platelet activation.

Bernard-Soulier syndrome: a flow cytometric analysis of membrane GP-Ib expression.

A case of Bernard-Soulier syndrome in a five-year-old female is presented. The diagnosis was confirmed by flow cytometric analysis of glycoprotein Ib (CD 42b) in addition to the patient's classic laboratory findings such as prolonged bleeding time, mild thrombocytopenia, large platelets and failure of platelet aggregation with ristocetin. Her parents and sibling had normal coagulation tests and CD 42b levels. It is emphasized that flow cytometric analysis is useful in the confirmation of congenital platelet function defects.

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.

Myelodysplastic syndrome in a patient with Werner's syndrome.

Werner's 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 Werner's 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.