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.

Impaired brachial endothelial function in patients with primary anti-phospholipid syndrome.

Although the precise pathophysiology of thrombosis is unknown in primary anti-phospholipid syndrome (PAPS), it is assumed that autoantibodies developed against endothelial cells and platelets might be one of the primary mechanisms. However, whether interaction between autoantibodies and endothelium leads to an impaired vasodilator response has not been investigated yet. In this study, we aimed to investigate the endothelial functions in patients with PAPS. Thirty-one patients with PAPS (22 female, nine male, mean age: 34.6+/-8.9 years) and 27 age- and sex-matched, healthy controls were included in the study. Brachial artery responses to reactive hyperaemia (endothelium-dependent dilatation) [EDD] and sublingual nitroglycerine (endothelium-independent dilatation) [EID] were measured by using high-resolution vascular ultrasound both in patients with PAPS and in the controls. The results were expressed as percentage of change in baseline values. Regarding cardiovascular risk factors, there was no significant difference between the two groups. EDD in patients with PAPS was significantly lower than those of controls (6.9+/-4.9 vs. 14.8+/-4.1%; p<0.0001). EID measurements were not significantly different between the groups. In the PAPS group, EDD in patients with arterial involvement (17 patients) was significantly lower than those of patients with venous involvement (12 patients) (4.6+/-3.9 vs. 7.4+/-4.1%; p = 0.02). This study showed that endothelial functions determined by using brachial artery ultrasound were impaired in patients with PAPS, and this was more prominent in the subgroup of patients with arterial involvement compared to patients with venous involvement.

Factor XIII Val34Leu polymorphism does not contribute to the prevention of thrombotic complications in patients with antiphospholipid syndrome.

The effect of thrombophilic mutations in the development of thrombosis in patients with antiphospholipid syndrome (APS) has been extensively investigated. Factor XIII (FXIII) Val34Leu polymorphism is a newly described polymorphism which is located in the three amino acids away from the thrombin activation site of the FXIII-A subunit. It has been reported that the Leu allele decreases the risk of both arterial and venous thrombosis. In the present study, we examined the association between the FXIII Val34Leu polymorphism and the development of thrombosis in patients with APS. Sixty APS patients with arterial and venous thrombosis, 22 antiphospholipid antibody (aPLA) positive patients with first trimester abortus and/or thrombocytopenia, 126 healthy controls, and 60 healthy subjects who were age- and sex-matched with thrombotic APS group were included into the study. FXIII Leu allele frequencies in the APS patients with thrombosis, aPLA-positive patients without thrombosis, healthy controls, and matched controls were 13.3, 16, 19.5, and 18.3%, respectively. When we compared Leu allele frequencies between APS patients with thrombosis and aPLA-positive patients without thrombosis, healthy controls or matched controls, we could not find any difference (chi2, p = 0.43, and P = 0.09, P = 0.67, respectively). Our results showed that the FXIII Leu allele has no protective effect in the development of thrombosis in APS.

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.

Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study.

The pathogenetic role and the clinical importance of the presence of antiphospholipid antibodies (APAs) in patients with immune thrombocytopenic purpura (ITP) are not clear. In this study, the prevalence and clinical significance of APAs were investigated in patients with ITP. Eighty-two newly diagnosed ITP patients were prospectively studied. They were evaluated for the presence of lupus anticoagulant (LA) and immunoglobulin G/M anticardiolipin antibodies (ACAs). Thirty-one patients (37.8%) were APA positive at diagnosis. No statistically significant differences were found between the APA-positive and APA-negative groups regarding gender, initial platelet counts, or response to methylprednisolone therapy. After 5 years of follow-up, cumulative thrombosis-free survival of APA-positive (n = 31) and APA-negative (n = 51) ITP patients was 39% and 97.7%, respectively. A significant difference was found between these groups by log-rank test (P =.0004). In addition, LA was an important risk marker for the development of thrombosis in ITP patients. After a median follow-up of 38 months, 14 ITP patients (45%) who had APA positivity developed clinical features (thrombosis or fetal losses) of antiphospholipid syndrome (APS). There were no differences between the APA-positive patients with and without APS regarding the initial platelet counts, response to the therapy, or ACA positivity. The positivity rate for LA was significantly higher in those patients with ITP who developed APS (chi(2): P =.0036; relative risk 7.15; 95% confidence interval, 1.7-47). In conclusion, this study indicates that a significant proportion of patients initially presenting with ITP and APA positivity developed APS. In patients with ITP, the persistent presence of APAs is an important risk factor for the development of APS.

Human polymorphism of P-selectin glycoprotein ligand 1 attributable to variable numbers of tandem decameric repeats in the mucinlike region.

Platelet GP Ibalpha and leukocyte P-selectin glycoprotein ligand 1 (PSGL-1) are membrane mucins with a number of structural and functional similarities. It was investigated whether, like GP Ibalpha, PSGL-1 is affected by a variable number of tandem repeat polymorphism in its mucin-like region. By polymerase chain reaction amplification of the genomic region encoding the PSGL-1 repeats, 3 allelic variants were identified in the human population. The 3 alleles-A, B, and C-from largest to smallest, contained 16, 15, and 14 decameric repeats, respectively, with the B variant lacking repeat 2 and the C variant retaining repeat 2 but lacking repeats 9 and 10. Allele frequencies were highest for the A variant and lowest for the C variant in the 2 populations studied (frequencies of 0.81, 0.17, and 0.02 in white persons and 0.65, 0.35, and 0.00 in Japanese). Thus, PSGL-1 is highly polymorphic and contains a structural polymorphism that potentially indicates functional variation in the human population.

The combined occurrence of macular amyloidosis and prurigo nodularis.

The association of prurigo nodularis (PN) and macular amyloidosis (MA) has not been reported before. Although pruritus related frictional trauma is a well-known cause of PN, its role in the development of MA has always been questioned. We herein report two cases with chronic liver disease and iron deficiency who concomitantly developed MA and PN lesions. Pruritus was the preceding factor and both lesions were confined to scratched areas. The association of two otherwise uncommon dermatoses in pruritic patients and their characteristic distribution might indicate an important role for pruritus-induced scratching in the pathogenesis of MA, too.

Ocular involvement in primary antiphospholipid syndrome. Ocular involvement in primary APS.

UNLABELLED: The purpose of this study is to evaluate the ocular findings in patients with the primary antiphospholipid syndrome (APS). PATIENTS AND METHODS: Twenty-two patients (44 eyes) with primary APS (17 women, 5 men) were examined. All patients were younger than 50 years (median age; 37.5 years). In 18 patients, fundus flourescein angiography was performed in addition to the ophthalmologic examination. RESULTS: Sixteen patients (72.7%) described visual symptoms. Anterior segment was normal in 19 patients (86.4%). Posterior segment abnormalities were observed in 15 patients (68.2%). Venous dilatation and tortuosity were the most common ocular findings. Retinal vascular occlusive disease was detected in 5 patients (22.7%). Flourescein angiography abnormalities were noted in 14 of the 18 patients (77.8%). The most common angiographic finding was pigment epithelial window defects. CONCLUSIONS: Our results indicate that posterior eye segment involvement is relatively common in the primary APS. It also seems that the screening for APS is important in young patients with retinal vascular occlusion, especially in those without conventional risk factors.