The clinical and pharmacoeconomic analysis of invasive aspergillosis in adult patients with haematological diseases.

Invasive pulmonary aspergillosis (IPA) poses major management problems for clinicians caring for patients with haematological diseases. The clinical courses of patients with IPA who had been hospitalised in Hematology Unit, Bone Marrow Transplantation Unit and Infectious Diseases and Clinical Microbiology Unit between 1998 and 2005, the efficacy and adverse effects and costs of antifungal drugs (conventional amphotericin B deoxycholate, liposomal amphotericin B, amphotericin B lipid complex and caspofungin) used in the therapy of these patients were analysed in this study. Ninety-three patients with IPA were reviewed retrospectively. Mean age of the patients was 40.4 +/- 15.1 years (range 14-70 years). Fifty-eight male patients and 35 female patients were included in the study. Manageable hypopotassemia, nausea/vomiting and headache were the most commonly observed side-effects during antifungal (AF) therapy. While it was not found to be statistically significant with regard to the mean time to resolution of fever (P = 0.8), it was found to be statistically significant with regard to radiological regression at 30th day, and mean duration of therapy between patients who were dead or alive (P < 0.05, P < 0.001). Total cost of AF therapy for 93 patients was found to be US$4 461 824 (minimum US$387-maximum US$279 023). Of this amount, US$4 272 845 represents the payment for AF drugs, US$188 979 the payment for other expenditures. Mean cost of therapy for a patient with IPA was found to be US$49 336. Although it seemed to be difficult, investigations should primarily focus on providing standardisation of parameters relating to the duration of AF therapy. Despite the less-than-optimal safety profile of CAB, it often remains to be the preferred first line option for the treatment of fungal infections because of its broad spectrum, activity and low acquisition cost.

T-cell large granular lymphocytic leukaemia: successful response to 2-deoxycoformycin.

We report a 25-year-old woman with T-cell large granular lymphocytic leukaemia presenting with severe neutropenia, anaemia and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3+, TCRgamma delta+, CD4-, CD5+, CD7+, CD8+, CD57+ large granular lymphocytes. Clonality was demonstrated with T-gamma polymerase chain reaction analysis which revealed clonal rearrangement of the TCRgamma chain gene. Cyclosporine, granulocyte colony-stimulating factor, methothrexate and a combination of cyclophosphamide, vincristine and prednisolone failed to correct the neutropenia and the anaemia. Finally, treatment with 2-deoxycoformycin resulted in both clinical and haemotological complete responses, despite molecular evidence of the persistence of the abnormal T-cell clone.

Hairy cell leukaemia presenting with ascites, pleural effusion and increased CA 125 serum level.

The body cavities are rarely involved in hairy cell leukaemia. Here we report a patient who had pancytopenia, hepatosplenomegaly, massive haemorrhagic ascites, pleural effusion at the left hemithorax and increased CA 125 serum level at the time of initial diagnosis. Laparoscopy showed multiple nodular white, opaque lesions on the omentum and on the parietal peritoneum. Laparoscopic biopsy of these lesions, and a bone marrow biopsy revealed a diffuse cellular infiltrate of tartrate-resistant acid phosphatase staining mononuclear cells. These mononuclear cells with irregular cytoplasmic protrusions were also found in the peripheral blood, in the ascites fluid and in the pleural effusion. The patient was treated with cladribine 0.1 mg/kg/day with continuous infusion for seven days. Three months after the treatment, the patient achieved a complete remission with normalisation of the peripheral blood count, bone marrow findings, CA 125 serum level, with no detectable ascites and/or pleural effusion.

Development of hairy cell leukemia in a patient with antiphospholipid syndrome.

We present a young woman who was diagnosed as primary antiphospholipid syndrome (deep vein thrombosis and pulmonary embolism in 1999; moderate thrombocytopenia with high-positive anticardiolipin ELISA tests in 2002, and cerebral thrombosis in 2003), and then developed hairy cell leukemia (massive splenomegaly, neutropenia, hairy cells in blood smear and bone marrow trephine biopsy in 2004). A partial remission was achieved with interferon-alpha 2a therapy. After the initiation of 2-chloro-deoxyadenosine therapy, splenomegaly disappeared, the percentage of hairy cells on the bone marrow reduced below 1%, platelet count returned to normal levels. After complete remission was achieved for hairy cell leukemia proved by bone marrow trephine biopsy, antiphospholipid antibodies were found to be negative, and no further thromboembolic complications and thrombocytopenia were seen. In our literature search, we found only six cases that had both antiphospholipid antibodies and hairy cell leukemia. Our case is the first case of antiphospholipid syndrome before the development of hairy cell leukemia. Both hairy cell leukemia and antiphospholipid syndrome responded to lymphocytotoxic treatment with 2-chloro-deoxyadenosine.

T-cell-rich B-cell lymphoma of the spleen presenting with severe hypersplenism.

We report a 19-year-old woman who was presented with B-symptoms, massive splenomegaly, hepatomegaly and hypersplenism. She underwent diagnostic/therapeutic splenectomy. Microscopically, the spleen showed a vaguely micronodular and diffuse proliferation of lymphoid cells in the white pulp that also involved the red pulp. On immunohistochemical staining, this proliferation consisted predominantly of CD3(+), CD7(+) small T cells with the presence of a minor population of CD15(-),CD30(-), CD20(+) large atypical B cells. A liver biopsy also showed a similar morphology to that seen in the spleen. After splenectomy, only the pancytopenia improved. A combined immunochemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) was utilized, which resulted in a complete remission.

Prognostic importance of soluble CD23 in B-cell chronic lymphocytic leukemia.

Soluble CD23 (sCD23) was proposed as a marker of disease activity and as an important prognostic parameter in B-cell chronic lymphocytic leukemia (B-CLL). In this study, prognostic significance of sCD23 in B-CLL was examined according to its temporal relationship with the known clinical parameters of the disease, CD38 and ZAP-70. Serum sCD23 levels of 36 B-CLL patients, followed up in our clinic between 1999 and 2005, and 15 healthy subjects were measured with enzyme-linked immunosorbent assay. The mean serum sCD23 level of the B-CLL patients (210.72 +/- 193.67 and 6-600 U/ml) was significantly higher than the control group (18.20 +/- 14.30 and 6-50 U/ml). Seventy-eight percent of the B-CLL patients with lymphocyte doubling time (LDT) <12 months and 24% of patients with LDT >12 months had high sCD23 levels (P = 0.008). Meanwhile, 81% of the patients with diffuse bone marrow infiltration and 33% of patients with nondiffuse infiltration had high levels of serum sCD23 (P = 0.029). A significant difference was found between B-CLL patients with Binet stages A and C (P = 0.009). Peripheral blood flow cytometry of the patients revealed a significant CD38 expression in patients with high serum sCD23 levels (P = 0.002). Similarly, an increased bone marrow zeta-chain associated protein kinase-70 (ZAP-70) expression was seen in patients with high serum sCD23 levels (P = 0.009, correlation co-efficient was 0.714). Cumulative and the progression free survivals of the patients with low serum sCD23 levels were 60.1 +/- 5.7 months [95% confidence interval (CI); 49.0-71.2] and 51.1 +/- 6.6 months (95% CI; 38.0-64.1), respectively. However, they were 43.8 +/- 6.5 months (95% CI; 31.0-56.6) and 26.5 +/- 6.4 months (95% CI; 14.0-39.1) in patients with high levels. Serum sCD23 is increased in B-CLL patients and can be used in the clinical follow-up of the disease in prediction of the tumor mass and prognosis.

Myeloid antigen expression provides favorable outcome in patients with adult acute lymphoblastic leukemia: a single-center study.

Between July 1992 and July 2001, 81 patients with de novo adult acute lymphoblastic leukemia (ALL) treated according to the German Multicenter Study Group for Adult ALL (GMALL) 01/81 protocol were evaluated in order to analyze the effect of aberrant myeloid antigen expression on prognosis. We observed myeloid antigen aberrant expression in 21 of the adult ALL cases. We did not observe any effect of aberrant myeloid antigen expression on the time to achieve remission, relapse rate, and death rate. After 5 years of follow-up, cumulative disease-free survival of myeloid antigen (My) (+) and My (-) adult ALL patients was 67% and 43%, respectively. These data were not found to be statistically significant (P=0.29), but we did find a statistically significant difference in overall survivals between these two groups (85% vs 50%) (P=0.05). Twenty-nine patients died and the remaining 52 patients were followed for a median of 31 months. We could not find any special effect of the known prognostic factors on prediction of relapse in multivariate analysis. However, myeloid antigen expression was the most significant factor, which affected long-term survival in our patients (P=0.01). These data indicate that myeloid antigen expression is useful for predicting a favorable outcome of adult patients with ALL.

Clonality of acquired primary pure red cell aplasia: effectiveness of antithymocyte globulin.

Primary pure red cell aplasia (PRCA) was diagnosed in two male patients, 65 and 69 years old respectively. In both, surface markers of peripheral blood nuclear cells revealed the presence of TCR alphabeta+ phenotype. Clonality of T cells was confirmed by the polymerase chain reaction in both patients, in whom, prednisone at a dose of 1 mg/kg/day improved the anemia and lower doses caused its renewal, resulting in the reappearance of the patient's transfusion requirement. On the other hand, the anemia seems to have been treated permanently (second case) with horse antithymocyte globulin (ATG) (20 mg/kg/day 1 to 8 +) since his hemoglobin was about 15 g/dl at the time of writing. In the first patient, the hemoglobin level was 10.5 g/dl one month after the administration of ATG (15 mg/kg/d 1 to 5 +), but unfortunately, the patient died because of a massive gastrointestinal bleeding on the fortieth day following this treatment. We, therefore, suggest that, patients with acquired primary PRCA should be screened to detect the presence of a T-cell clone and recommend that, treatment should start earlier with ATG, if the PRCA is due to a T-cell clonal disorder.

Leukemia in a patient treated with growth hormone.

It is well known that growth hormone (GH) therapy is associated with increased risk of development of malignant tumors, especially leukemia. In the case presented, growth hormone treatment was initiated in a 25-year-old patient with hypopituitarism. After 4 months of therapy with thrice a week injections of rhGH, acute myelogenous leukemia developed. It was thought that no clearcut evidence existed to establish a relationship between the growth hormone treatment and development of acute leukemia.

Imaging features of thalassemia.

Thalassemia is a kind of chronic, inherited, microcytic anemia characterized by defective hemoglobin synthesis and ineffective erythropoiesis. In all thalassemias clinical features that result from anemia, transfusional, and absorptive iron overload are similar but vary in severity. The radiographic features of beta-thalassemia are due in large part to marrow hyperplasia. Markedly expanded marrow space lead to various skeletal manifestations including spine, skull, facial bones, and ribs. Extramedullary hematopoiesis (ExmH), hemosiderosis, and cholelithiasis are among the non-skeletal manifestations of thalassemia. The skeletal X-ray findings show characteristics of chronic overactivity of the marrow. In this article both skeletal and non-skeletal manifestations of thalassemia are discussed with an overview of X-ray findings, including MRI and CT findings.

[Arteriovenous fistula of the lung: a rare cause of erythrocytosis]. / Arteriovenöse Fistel der Lunge: Eine seltene Ursache einer Polyglobulie.

Various chronic pulmonary diseases can cause hypoxia mediated erythrocytosis. We report on a 46 year old male patient presenting with erythrocytosis, in whom a pulmonary arteriovenous fistula on the basis of a vascular malformation was identified as a rare cause of hypoxic erythrocytosis. Thus, congenital pulmonary vascular malformations can become clinically manifest in advanced age.

Anemia and thrombocytopenia due to parvovirus B-19 infection in a pregnant woman.

Anemia and thrombocytopenia in a patient with parvovirus B-19 and hepatitis C infection is reported. A seven month-pregnant 20 year-old patient had been first found to be anemic and thrombocytopenic 40 days before admission to our hospital and she had been given methylprednisolone and red cell transfusions. She gave birth to a healthy baby after only eight months of pregnancy. Ten days after delivery she was admitted to our hospital because of anemia and thrombocytopenia which did not respond to treatment. On admission, the blood count showed hemoglobin 8.1 g/dL, hematocrit 23.7%, white blood cells 11,200/microL, platelets 1000/microL, and reticulocytes 0.6%. Bone marrow smear and biopsy revealed erythroblastopenia and the absence of megakaryocytes. Liver enzymes were also high (alanine aminotransferase 1469 Units/L and aspartate aminotransferase 981 Units/L). In serologic studies PVB-19 IgM was found to be positive and hepatitis C virus RNA was detected. Red cell and platelet values returned to normal levels after cessation of methylprednisolone and concomitantly PVB-19 IgG was found positive in association with IgM in repeated determinations. PVB-19 was thought to be responsible for both anemia and thrombocytopenia.

Survey on haemoglobin variants, beta thalassaemia, glucose-6-phosphate dehydrogenase deficiency, and haptoglobin types in Turks from western Thrace.

A total of 102 apparently healthy and randomly selected Turks who either immigrated from Western Thrace or were still living there were studied for haemoglobin variants, high Hb A2 beta thalassaemia, G6PD deficiency, and haptoglobin types. The incidence of haemoglobins S and O Arab were 2.9 and 3.9% respectively. The incidence of high A2 beta thalassaemia was 10.8% and that of G6PD deficiency 5%. The gene frequencies of Hp1 and Hp2 were 0.326 and 0.674, respectively.

Haptoglobin and transferrin types in Eti-Turks.

Haptoglobin and transferrin types were examined in Eti-Turks. The Hp1 frequency was 0.26. With the exception of two individuals with transferrin D, only the transferrin C was observed. The gene frequencies were in the range of most of the Asiatic populations including Turks.