Subchronic methionine load induces oxidative stress and provokes biochemical and histological changes in the rat liver tissue.

The aim of this study was to assess the effects of L-cysteine (Cys) (7 mg/kg) and N-acetyl-L-cysteine (NAC) (50 mg/kg) in the rat liver caused by subchronic i.p. application of methionine (Met) (0.8 mmol/kg) during 21 days. Malondialdehyde (MDA) concentration, glutathione content (GSH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and acetylcholinesterase (AchE) activities were determined in the liver tissue and activities of liver enzymes (AST, ALT, ALP, and GGT) and concentrations of total proteins and albumin were determinated in plasma/serum. Catalase, superoxide dismutase, and acetylcholinesterase activities were increased by Cys and NAC. Met caused periportal mononuclear infiltration and rare focal necrosis of hepatocytes. In Cys- and NAC-supplemented groups, intracellular edema and microvesicular fatty changes without necrosis were noticed. We observed decrease of AST, ALT, and ALP activity in the methionine-treated group. Our results indicate that Cys and NAC application can increase activity of antioxidative enzymes and prevent intensive histological changes in liver in condition of subchronic methionine exposure.

The effect of subchronic supplementation with folic acid and l-arginine on homocysteine-induced seizures.

The aim of the present study was to examine the effect of subchronic co-administration of folic acid (F) and l-arginine (A) on behavioural and electroencephalographic (EEG) characteristics of dl homocysteine thiolactone (H) induced seizures in adult rats. The activity of membrane ATPases in different brain regions were also investigated. Rats were treated with F, A, or vehicle for 15 days (regimen: F 5 mg/kg + A 500 mg/kg (F5A500); F 10 mg/kg + A 300 mg/kg (F10A300)). Seizures were elicited by convulsive dose of H (H, F5A500H, F10A300H) Subchronic supplementation with F and A did not affect seizure incidence, number of seizure episodes, and severity in F5A500H and F10A300H groups vs. H group. However, a tendency to increase latency and decrease the number of seizure episodes was noticed in the F10A300H group. EEG mean spectral power densities during ictal periods were significantly lower in F10A300H vs. H group. The activity of Na+/K+-ATPase and Mg2+-ATPase was significantly increased in almost all examined structures in rats treated with F and A. We can conclude that subchronic supplementation with folic acid and l-arginine has an antiepileptic effect in dl homocysteine thiolactone induced epilepsy.

Evaluation of Levothyroxine Bioavailability after Oral Administration of a Fixed Combination of Soy Isoflavones in Post-menopausal Female Volunteers.

BACKGROUND: Post-menopausal women under treatment with levothyroxine for their medical conditions may take concomitantly dietary supplements containing soy isoflavones in combination to treat their post-menopausal symptoms. The aim of this study was to investigate the effect of a fixed combination of soy isoflavones on the oral bioavailability of levothyroxine in post-menopausal female volunteers. METHODS: 12 healthy post-menopausal female, who were on stable oral levothyroxine as replacement/supplementation therapy for hypothyroidism, received a single recommended oral dose of a food supplement containing 60 mg of soy isoflavones (>19% genistin and daidzin) concomitantly with (test) and 6 h later (reference) the administration of levothyroxine in a randomized, open label, crossover fashion. Plasma concentrations of levothyroxine and soy isoflavones (daidzin, daidzein, genistin, genistein, S-equol) were determined by LC-MS/MS. Pharmacokinetic (PK) parameters were determined by non-compartmental analysis. No effect of soy isoflavones was assumed if the 90% confidence intervals (CIs) for the estimated ratio test/reference was included in the acceptance limits 0.80-1.25 for PK parameters Cmax and AUCt. RESULTS: The test/reference ratios Cmax and AUCt of levothyroxine were very close to unity (1.02 and 0.99, respectively) and the corresponding 90% CIs (0.99-1.04 and 0.88-1.12, respectively) fell entirely within the acceptance bioequivalence limits. CONCLUSION: The combination of soy isoflavones used in the present investigation does not affect the rate and extent of levothyroxine absorption when administered concomitantly in post-menopausal women.

The effect of subchronic supplementation with folic acid on homocysteine induced seizures.

Influence of folic acid on the CNS is still unclear. Folate has a neuroprotective effect, while on the other hand excess folate can exacerbate seizures in epileptics. The aim of the present study was to examine the effect of subchronic administration of folic acid on behavioural and electroencephalographic (EEG) characteristics of DL homocysteine thiolactone induced seizures in adult rats. The activity of Na⁺/K⁺-ATPase and Mg²âº-ATPase in different brain regions was investigated. Adult male Wistar rats were divided into groups: 1. Controls (C, 0.9% NaCl); 2. DL homocysteine-thiolactone 8.0 mmol/kg (H); 3. Subchronic supplementation with folic acid 5 mg/kg for 7 days (F) and 4. Subchronic supplementation with F + single dose of H (FH). Seizure behaviour was assessed by incidence, latency, number and intensity of seizure episodes. Seizure severity was described by a descriptive scale with grades 0-4. For EEG recordings, three gold-plated recording electrodes were implanted into the skull. Subchronic supplementation with folic acid did not affect seizure incidence, median number of seizure episodes and severity in FH, comparison with H (p > 0.05). The majority of seizure episodes in all groups were of grade 2. There were no significant differences in lethal outcomes at 24 h upon H injection in the FH vs. H group. The activity of Na⁺/K⁺-ATPase and Mg²âº-ATPase was significantly increased in almost all examined structures in the FH vs. H group. Subchronic folic acid administration did not exacerbate H induced seizures and completely recovered the activity of ATPases.

Electrolytes based on alkoxysilyl-functionalized ionic liquids: viscoelastic properties and conductivity.

Ionic liquids can be successfully used as electrolytes in electrochemical devices when they are in their quasi-solid state. Among several methods of solidification, a sol-gel process was chosen and a set of alkoxysilyl-functionalized iodide imidazolium-based ionic liquids were synthesized. The electrolytes were prepared by mixing these ionic liquids with a non-polymerisable ionic liquid (1-methyl-3-propylimidazolium iodide (MPIm(+)I(-))). Iodine was dissolved in an electrolyte matrix in order to form an I3(-)/I(-) redox couple. The change of the structure from sol to gel was followed by rheological tests in order to show the effect of different rheological parameters on the gelation process. The solvolysis with glacial acetic acid and condensation were followed by rheological experiments on the samples taken from a batch, and in situ on the rheometer. The formed three-dimensional sol-gel networks of various alkoxysilyl-functionalized ionic liquids differed in their microstructures and viscoelastic properties that were correlated with conductivity. The results show that the conductivity of approximately 10(-3) S cm(-1) at room temperature was achieved for the gels with relatively high values of elastic modulus and noticeable viscous contribution. It is shown that not only the viscosity but also the viscoelastic behavior and especially the relationship between viscous and elastic moduli (phase shift) together with the time of gelation are essential for the high conductivity of electrolytes.

Exercise decreases susceptibility to homocysteine seizures: the role of oxidative stress.

The aim of the study was to examine the effects of chronic exercise training on seizures induced by homocysteine thiolactone (HCT) in adult rats. Rats were assigned to: sedentary control; exercise control; sedentary+HCT; exercise+HCT group. Animals in the exercise groups ran 30 min daily on a treadmill for 30 consecutive days (belt speed 20 m/min), while sedentary rats spent the same time on the treadmill (speed 0 m/min). On the 31st day, the HCT groups received HCT (8.0 mmol/kg), while the control groups received vehicle. Afterwards, convulsive behavior and EEG activity were registered. Lipid peroxidation, superoxide dismutase (SOD) and catalase (CAT) activity were ascertained in the rat hippocampus. No signs of seizures were registered in sedentary and exercise control rats. Seizure latency was increased, while number of seizure episodes and spike-and-wave discharges (SWD) in EEG were decreased in the exercise+HCT compared to the sedentary+HCT group. Seizure incidence, the severity thereof and duration of SWDs were not significantly different between these groups. Exercise partly prevented increase of lipid peroxidation and decrease of the SOD and CAT activity after HCT administration. These results indicate beneficial effects of exercise in model of HCT-induced seizures in rats, what could be, at least in part, a consequence of improved antioxidant enzymes activity.

Primary cutaneous large B-cell non-Hodgkin lymphoma in first-degree relatives.

Primary cutaneous non-Hodgkin's lymphoma is a heterogeneous group of lymphoproliferative disorders characterized by indolent course, virtually exclusive skin involvement and the absence of systemic disease. We present two brothers, whose mother died of gastric diffuse large B-cell lymphoma, in whom in a period of 4 years primary cutaneous large B-cell non-Hodgkin lymphoma of the skin of the head was diagnosed. They were treated with immunochemotherapy according to R-CHOP protocol (rituximab and adriblastine, cyclophosphamide, oncovine and prednisone) achieving a complete remission. The possible etiological mechanism of this familial lymphoma occurrence is discussed.

Mixed phenotype acute leukemia of T/myeloid type with a prominent cellular heterogeneity and unique karyotypic aberration 45,XY, dic(11;17).

INTRODUCTION: A 26-yr-old male patient with mixed phenotype acute leukemia of T/myeloid type with prominent leukemic cell heterogeneity, and the presence of a so far unreported karyotype aberration in this type of acute leukemia 45,XY, dic(11;17)(11qter→11p11.2::17p11.2→17qter) is presented. METHODS: Flow immunocytometry was performed by direct multicolor immunofluorescent technique on bone marrow aspirates. Cytogenetic analyses were performed using G-banding method by direct preparation of unstimulated bone marrow cells and following 24 hours of culture in RPMI 1540 culture medium with 25% fetal calf serum at 37°C RESULTS: The flow immunocytometry of bone marrow nucleated cells revealed the existance of three distinct blast cell populations with overlapping immunophenotypes. Predominant blast cell population had an early myeloid phenotype and aberrant expression of CD7 antigen (HLA-DR(+), CD34(+), anti-MPO(+), CD117(+), CD33(+), CD13(+), CD7(+low), cyCD3(-), TdT(-)). The other two blast cell populations, smaller in cell diameter and less sizable in cell proportion, both shared the T-lymphoid features. The patient was treated with ADE protocol (etoposide, cytarabine and doxorubicine). A complete remission was achieved and lasted 5 months. CONCLUSION: A case of MPAL with complex biological features, 45,XY, dic(11;17)(11qter→11p11.2::17p11.2→17qter) karyotype and an aggressive, therapy-resistant clinical course, is presented.

Clinical efficacy, safety and pharmacokinetic properties of the plasma-derived factor IX concentrate Haemonine in previously treated patients with severe haemophilia B.

Plasma-derived factor IX (FIX) concentrate remains an important choice for replacement therapy in haemophilia B patients. Haemonine is a high purity double-virus inactivated human plasma-derived coagulation FIX concentrate (pdFIX). Aim was to evaluate the clinical efficacy, safety and pharmacokinetic properties of Haemonine in three prospective, open-label uncontrolled studies and a compassionate use program in previously treated patients with severe haemophilia B. Long-term efficacy and safety were investigated in 29 patients treated prophylactically and, in addition, treatment on-demand (TOD) in the case of acute haemorrhage. Pharmacokinetic properties were assessed in 14 patients at baseline and after 3 months of regular treatment. Pharmacokinetic parameters were in accordance with published data and remained nearly unchanged over time, notably recovery and half-life. Mean terminal elimination half-life was 27.6 h and 25.0 h, mean incremental recovery (IU dL(-1) /IU kg(-1)) was 1.55 and 1.60, at baseline and 3 months, respectively. Haemonine was shown to be effective in preventing and controlling bleeds. 55.2% (16/29) of patients were free of bleeds under prophylaxis. 38 haemorrhages occurred, 42% (16/38) required treatment and 87.5% (14/16) resolved after a single infusion, 12.5% after 2 infusions. All responses reported on haemorrhages were rated as 'excellent' or 'good'. Moreover, 'excellent' haemostatic efficacy was demonstrated in 12 surgeries with no complications. Few adverse events (AEs) and no thrombogenic complication, nor induction of FIX inhibitory antibodies were observed. Haemonine is effective, safe and well tolerated in long-term prophylaxis, TOD and when applied after minor and major surgeries.

Therapy-related myelodysplastic syndrome and acute myeloid leukemia in patients with chronic lymphocytic leukemia treated with fludarabine and cyclophosphamide.

We retrospectively studied four cases of t-MDS/AML among 210 (1.9%) consecutive patients with CLL treated at a single center with fludarabine and cyclophosphamide (FC) either as the first- or second-line therapy. The median follow-up of the whole cohort of patients was 46months (range: 7-60). Two of these patients (2/130, 1.7%) had been treated with FC only, and two more (2/80, 2.3%) with CHOP and CHOP+FND, respectively, prior to FC. The median age was 61.5years (range: 49-71); three were male. They developed t-MDS/AML after a median latency period of 41months (range: 7-56) from the FC completion. Chromosomal aberrations with an adverse prognostic impact were present in the karyotype of all four patients, including abnormalities of chromosome 5 in three of them, and a rare chromosomal translocation in one patient. Median survival after t-MDS/AML diagnosis was 4months (range: 2-8). Although the agents administered prior to FC make it difficult to assess the risk of t-MDS/AML attributable to FC, this report might be a valuable addition to the literature.

Mycophenolate mophetil therapy for chronic immune thrombocytopenic purpura resistant to steroids, immunosuppressants, and/or splenectomy in adults.

Treatment options are limited in patients with chronic immune thrombocytopenic purpura (ITP) which has been unresponsive to corticosteroids and/or splenectomy. Mycophenolate mophetil (MMF) is effective in many autoimmune disorders including severe and refractory ITP through its targeting of T-cell and B-cell lymphocytes. We report on the efficacy of MMF (1.5-2 g/day) in 16 adults with severe steroid-resistant ITP. MMF was administered for at least 12 weeks (median 37 weeks, range 14-64 weeks). Patients comprised of 10 females and six males, with median pre-treatment platelet counts of 8 × 10(9)/L, median age of 55 years, median ITP duration of 58 months and a median of four prior treatments (range 3-8); nine had been previously splenectomized. Eleven patients (69%) responded after 12 weeks of MMF: 6 (55%) achieving complete remission (CR) and five (45%) achieved partial remission (PR). MMF therapeutic responses were better in those patients who had had fewer prior treatments (p<0.05), and were independent of patient age, sex, disease duration, and splenectomy status (p>0.05). Five of the 11 responders (45%; 3CR/2PR) had sustained remissions; however, six responders (55%; 3CR/3PR) relapsed after median of 14 weeks (range 9-20). Three of the six relapsing patients responded to MMF reinstitution achieving stabile PRs; three were left untreated as none had further bleeding and their platelets remained at "safe" levels (median 30 × 10(9)/L). The MMF treatment was well tolerated; one heavily pretreated patient developed a bronchopneumonia and a second had an episode of diarrhea. MMF used as a second-line agent can produce a sustained response in severe ITP which has been unresponsive to steroid and/or splenectomy without major toxicity.

Specific skin lesions in hairy cell leukemia at presentation: case report and review of literature.

Skin involvement in hairy cell leukemia (HCL) at presentation is a relatively rare manifestation of the disease. A 60-year-old male patient in whom cutaneous lesions were the initial manifestation of hairy cell leukemia together with leukocytosis, monocytopenia, massive splenomegaly, and leukemic maculopapulous infiltration of the almost whole skin is described. The present case is the forth mentioned in the literature with specify of leukocytosis in peripheral blood, consisting mostly of hairy cells. The patient was treated with two courses of 2-chlorodeoxiadenosine (2-CdA, Cladribine) and splenectomy and after this cutaneous lesion disappeared and general condition is improved.

Molecular response to imatinib in patient with Ph negative p190 BCR-ABL transcript positive chronic myeloid leukemia with cyclic leukocytosis.

An atypical case of Philadelphia (Ph) negative, e1a2 BCR-ABL transcript positive chronic myeloid leukemia (CML) characterized with cyclic periodic leukocytosis and spontaneous remissions is reported. The patient was treated with imatinib and good hematology response with molecular remission was achieved. So far, only few Ph positive CML patients expressing p190 BCR-ABL protein and different clinical characteristics and treatment have been described in the literature. This is the first report of Philadelphia negative, p190 BCR-ABL positive CML with cyclic spontaneous oscillation of white blood cell count (WBC), and excellent response to imatinib treatment.

Antiribosomal-P protein antibodies in a patient with systemic lupus erythematosus and non-Hodgkin's lymphoma: more than coincidental finding?

Patients with systemic lupus erythematosus (SLE) are at an increased risk of lymphomas, but mechanisms underlying this association are obscure. Recently, it has been shown that antiribosomal-P protein (anti-P) antibodies cross-react with phospholipids and enhance the production of cytokines which may influence lymphomagenesis. We report a 46-year-old woman who suffered high grade diffuse large B-cell non-Hodgkin's lymphoma (DLBCL) 28 months after the diagnosis of SLE. Development of lymphoma was associated with occurrence of serum monoclonal IgM, and pronounced prolongation of phospholipid-dependent clotting tests. Anti-P IgG antibodies were highly positive both on HEp-2 cells and in ELISA test. Anticardiolipin, anti-beta2 glycoprotein I, and antiprothrombin IgM antibodies have also been found in high concentrations. Complete remission of DLBCL and SLE, with normalisation of clotting tests, and disappearance of M component was achieved with administration of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. The progression of SLE to DLBCL associated with presence of anti-P antibodies has not been previously reported. This association may not be coincidental, but further investigations are required to confirm this hypothesis.

Molecular characteristics and prognostic significance of Bcl-2/IgH gene rearrangement in Serbian follicular lymphoma patients.

Follicular lymphoma (FL) is characterized by the presence of a t(14;18) chromosomal translocation that results in overexpression of bcl-2 protein. Bcl-2/IgH gene rearrangement is detected in 80-90% of follicular lymphomas in Western countries. The aim of this study was to analyze the bcl-2/IgH rearrangement in FL lymphoma patients in Serbia, by PCR technique, correlate molecular findings with clinical characteristics and outcome and assess the prognostic significance of these rearrangements. One hundred-seven patients (median age, 54 years; male/female ratio:60/47) diagnosed with FL were included in the study. DNA samples were obtained from paraffin embedded lymphoid tissue of patients. Bcl-2/IgH rearrangement was assessed for the major breakpoint region (MBR), 5' MBR and the minor cluster region (mcr) breakpoints by PCR technique. We detected a t(14;18) in 81.3% (87/107) of patients. The distribution of bcl-2-IgH rearrangement was as follows: 88,5% (77/87) in MBR breakpoint, 10,35% (9/87) in 5' MBR, whereas mcr bcl-2-IgH rearrangement was observed in one patient (1.15%). No rearrangements were detected in remaining 20 patients (18.7%). This is the first analyses of the frequency of the bcl-2/IgH gene rearrangement in Serbian FL patients, as well as in Eastern European countries. There was no correlation between presence of bcl-2/IgH gene rearrangement and clinical outcome of disease. Incidence of bcl-2/IgH gene rearrangement in Serbian FL patients is relatively high, and similar to frequency in Western countries. Presence of this rearrangement in tumor tissue is not of prognostic significance.

Triple-way therapeutic approach for paraganglioma-dependent erythrocytosis: drugs and surgery plus "multi-manner" apheresis.

Paragangliomas are tumors arising from the extra-adrenal paragangliar neural crest cells. The sympathoadrenal neuroendocrine system consists of extra-adrenal paragangliar cellular layer along the paravertebral and para-aortic axis, and the adrenal medullae. Paraganglioma should be included in the differential diagnosis of secondary erythrocytosis due to its possible ectopic erythropoietin (EPO) secretion. Thus, in this report we present a 24-year-old female patient with onset of unregulated ectopic EPO secretion, and consecutive erythrocytosis followed by hypertension, secondary to paraganglioma of multifocal retroperitoneal localization. Clinical, laboratory, and radiological investigations confirmed both an elevated EPO level and the presence of multiple paraganglioma. This paraneoplastic-mediated medical condition with high risk of cellular hyperviscosity syndrome (CHVS) requires prompt diagnosis and rapid therapeutic interventions. Initially, simple phlebotomy procedures were used; following that, tumors were surgically removed. In the course of the disease, this tumor relapsed, and urgent apheresis, as a treatment of life-threatening state, was used. The therapy performed resulted in a rapid blood viscosity depletion and a significant (P < 0.01) serum EPO reduction, as well as the general clinical benefit. Therefore, we conclude that the use of our own "multi-manner" apheresis (erythrocythapheresis plus plasma exchange), for long-time interval (until further causative therapy), effectively cross-bridged the possible hazards of EPO-dependent CHVS.

Expression of VEGF and microvessel density in patients with multiple myeloma: clinical and prognostic significance.

The conflicting data are reported on the clinical significance of VEGF deregulation and intensity of angiogenesis in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of VEGF expression and microvessel density (MVD) in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of VEGF and MVD was analyzed using standard immunohistochemical method (antibodies against VEGF and CD34, respectively) on B5-fixed and routinely processed paraffin-embedded bone marrow specimens. MVD was estimated by counting the number of microvessels in three "hot spots" at 400x magnification. VEGF immunoreactivity was estimated on the basis of intensity and percentage of positive plasma cells. VEGF was expressed in 47/59 (79.7%) specimens. There was no significant correlation between VEGF overexpression and age, clinical stage, the extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, and albumins, the extent of bone marrow infiltration, histological grade, and proliferative activity index (measured with Ki-67 immunoreactivity). No significant difference was observed regarding the overall survival between VEGF-positive and VEGF-negative patients (29 vs. 34 months, P = 0.8). Median MVD was 15, ranging from 1 to 89 microvessels per three "hot spots". There was significant correlation between MVD and histological grade, the extent of bone marrow infiltration, and proliferative activity. Significant difference was observed regarding the overall survival between patients with low MVD (<15) and patients with high MVD (> or = 15) (46 vs. 22 months, P = 0.009; univariate analysis). The results of this study did not reveal clinical significance of VEGF overexpression in multiple myeloma. On the contrary, the extent of bone marrow angiogenesis is an indicator of biological potency of malignant clone and a predictor of poor survival in newly diagnosed myeloma.

Malignant histiocytosis with central nervous system involvement and hepatic mucinous cystadenoma in a single patient with review of the literature.

Malignant histiocytosis is a rare neoplasm of the reticuloendothelial system characterized by neoplastic proliferation of tissue histiocytes. We report a case of malignant histiocytosis in a 64-year-old female initially operated on for a mucinous cystadenoma of her liver. Four months after the operation, skin induration on the neck and anterior thoracic wall and systemic lymphadenopathy were noted. Histology and immunohistochemistry of the lymph node and bone marrow specimens showed extensive infiltration with atypical cells, resembling malignant histiocytes (CD45, CD45RO, CD11c, CD68, lysozyme, antitrypsin and alpha1-antichymotrypsin positive; CD1, CD35, B-cell and T-cells markers negative). She was treated with vinblastine, methotrexate and dexamethasone (3 cycles) without response. The therapy was switched to CHOP (cyclophosphamide, vincristine, doxorubicin, and prednisone) with disappearance of lymphadenopathy. Bone marrow infiltration by histiocytes was reduced to 20%. Two months after completion of 8 cycles of CHOP she experienced severe headaches, vomiting, loss of consciousness, and developed paraparesis. A CT scan of the brain was normal but the cerebrospinal fluid cytology showed presence of histiocytes. The patient was then treated with intrathecal methotrexate, prednisolone and cytosine-arabinoside and systemic chemotherapy with etoposide and cyclophosphamide. Her condition improved, she became conscious, her headache diminished, she became mobile but skin and nodal lesions reappeared along with extensive marrow histiocytic infiltration. She finally died 22 months after diagnosis.

Immunophenotypic profile and clinical characteristics in patients with advanced stage mantle cell lymphoma.

The objective of this study was to evaluate immunophenotypic profile along with clinical follow-up in patients with advanced stage mantle cell lymphoma (MCL), and their possible influence on overall survival (OS). Bone marrow (BM) cell and/or peripheral blood mononuclear cell flow cytometric analyses of the following antigens were performed: HLA-DR, CD19, CD20, CD22, CD23, CD25, CD10, SmIg, kappa, lambda, CD79b, CD38, FMC7, CD3, CD2, and CD5. There were 14 patients in IV CS, and 26 patients in CS V. All patients were treated with CHOP. Immunological markers showed a typical phenotype (CD5+ CD23-, Cyclin D1) in all cases. Pathohistological type of BM infiltration was predominantly diffuse (72.5%), and in remainder of patients, nodular. Comparison of patients with leukemic phase of MCL with CSIV (BM), has shown significantly higher expression of CD19, CD20, and CD23, followed by permanently negative expression of CD23. Patients with blastic variant of MCL had higher expression of CD23, compared to typical MCL (P < 0.001). Median OS was 20 months, and there were no significant OS-differences between CS IV and leukemic phase patients. Survival analyses showed that negative prognostic influence had high IPI (P < 0.01), presence of extranodal localization (P < 0.01), and diffuse type of BM involvement (P < 0.01). Using Cox regression according to OS, IPI had independent prognostic value (P < 0.001). Our results demonstrated that in the advanced MCL patients the most powerful prognostic factor was IPI, while extranodal localization and type of BM infiltration were of a limited value.

Systemic lupus Erythematosus and IgA multiple myeloma: a rare association?

The coexistence of systemic lupus Erythematosus (SLE) and multiple myeloma (MM) is uncommon and the pathogenetic mechanisms underlying this association remain unclear. We report the case of a woman who was diagnosed with SLE in 1993 aged 57, then developing IgA lambda type MM in the IIB clinical stage 7 years later. The SLE was treated successfully with methylprednisolone and chloroquine, and low dose maintenance steroid was continued with bisphosphonate protection until December 1994 when she suffered multiple vertebral fractures. She continued to receive 4 mg alternate day methylprednisolone and calcitonin until she decided to discontinue her own treatment 2 years later. In 2000, while still in stable SLE remission, she was diagnosed with MM. Protein electrophoresis revealed the IgA lambda paraprotein (40.5 g/l) and she had a Bence Jones (BJ) proteinuria of the lambda light chain type. Bone marrow trephine biopsy revealed a massive patchy infiltrate of abnormal plasmocytes (70%), while an extensive x-ray skeletal survey did not show any new fractures or osteolysis. The patient was treated according to the VMCP protocol without attaining a plateau phase. There was a similar poor clinical response to second and third line treatments (VAD, Thalidomide, Melphalan, and high dose dexamethasone). After 4 years of refractory disease the patient died from severe bilateral pneumonia. This case is discussed with reference to the literature.