Effects of single-agent bortezomib as post-transplant consolidation therapy on multiple myeloma-related bone disease: a randomized phase II study.

This phase II study explored the effects of bortezomib consolidation versus observation on myeloma-related bone disease in patients who had a partial response or better after frontline high-dose therapy and autologous stem cell transplantation. Patients were randomized to receive four 35-day cycles of bortezomib 1·6 mg/m2 intravenously on days 1, 8, 15 and 22, or an equivalent observation period, and followed up for disease status/survival. The modified intent-to-treat population included 104 patients (51 bortezomib, 53 observation). There were no meaningful differences in the primary endpoint of change from baseline to end of treatment in bone mineral density (BMD). End-of-treatment rates (bortezomib versus observation) of complete response/stringent complete response were 22% vs. 11% (P = 0·19), very good partial response or better of 80% vs. 68% (P = 0·17), and progressive disease of 8% vs. 23% (P = 0·06); median progression-free survival was 44·9 months vs. 21·8 months (P = 0·22). Adverse events observed ≥15% more frequently with bortezomib versus observation were diarrhoea (37% vs. 0), peripheral sensory neuropathy (20% vs. 4%), nausea (18% vs. 0) and vomiting (16% vs. 0). Compared with observation, bortezomib appeared to have little impact on bone metabolism/health, but was associated with trends for improved myeloma response and survival.

The role of the nurses and technicians for stem cell mobilisation and collection.

Stem Cell Transplantation is last chance for some patients and they enter the unit highly hopeful for their life. Although the physicians, medical director of unit are the observable part of iceberg, which is on the surface, nurses and the other members of team are like the huge invisible part of iceberg. If they are not educated well increased mortality rates are inevitable. This article summarises the role of nurses well to the fore and technicians.

The effect of trans-resveratrol on platelet-neutrophil complex formation and neutrophil burst in hypercholesterolemic rats.

Transresveratrol (t-resveratrol; 3,5,4'-trihydroxy-trans-stilbene) is a polyphenolic compound found in fresh grapes, grape juice and wine, and has been found to reduce the total cholesterol level in hypercholesterolemic rats. The objective of the present study was to assess the effects of t-resveratrol on platelet-neutrophil complex formation and neutrophil reactive oxygen species (ROS) status in control and hypercholesterolemic rats using a modified flow cytometric method. Rats (n=80) were divided into five groups (control, ethanol, resveratrol, hypercholesterolemic and resveratrol-administered hypercholesterolemic groups), comprising 16 animals per group. Serum levels of lipids and H2O2 were determined using commercially available kits, while platelet-neutrophil complex formation and neutrophil ROS status were determined using a modified flow cytometric method. Serum total cholesterol and low-density lipoprotein cholesterol levels were found to be increased and the high-density lipoprotein cholesterol level was found to be decreased in the HC group compared with the control group (P<0.001). Treatment of HC rats with t-resveratrol significantly lowered total cholesterol and low-density lipoprotein cholesterol levels (P<0.001). In the hypercholesterolemic group, levels of serum H2O2 platelet-neutrophil complex formation and neutrophil ROS status were significantly increased (P<0.001). On the other hand, in the resveratrol-administered hypercholesterolemic group, serum H2O2 levels, platelet-neutrophil complex formation and neutrophil ROS status were decreased compared with the hypercholesterolemic group (P<0.001). Serum H2O2 levels, platelet-neutrophil complex and neutrophil ROS status were positively correlated with one another. The present study is the first to demonstrate the protective effect of t-resveratrol against hypercholesterolemia-induced platelet-neutrophil complex formation and neutrophil ROS burst. Further investigations on its plausible role in antihypercholesterolemic treatment are warranted.

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.

The association between inherited thrombophilias and pregnancy-related hypertension recurrence.

PURPOSE: The aim of this study was to determine the association between inherited thrombophilias and pregnancy-related hypertension recurrence. METHODS: In this case-control study, blood samples were obtained from patients who had at least two pregnancies complicated with pregnancy-related hypertension (n = 41) and healthy, normotensive pregnancies delivered without any complication (n = 38). Following the DNA extraction, samples were tested for factor V Leiden, prothrombin G20210A and homozygous methylene tetrahydrofolate reductase (MTHFR) C677T mutations using reverse hybridization method. RESULTS: Common inherited thrombophilias were present in 26.8% of women with recurrent pregnancy-related hypertension group and 23.7% of control subjects (odds ratio 1.1; 95% confidence interval, 0.6-1.9). No significant difference was observed between two groups in terms of factor V Leiden, prothrombin G20210A and MTHFR C677T mutations. CONCLUSION: Our data suggest that factor V Leiden, prothrombin G20210A and MTHFR C677T mutations are not associated with pregnancy-related hypertension recurrence.

Aspergillus alliaceus and Aspergillus flavus co-infection in an acute myeloid leukemia patient.

We report a case of a pulmonary infection caused by Aspergillus flavus and Aspergillus alliaceus in an acute myeloid leukemia patient. These isolates were identified using traditional and sequencing-based molecular methods.

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.

Microsatellite instability is a common finding in multiple myeloma.

PURPOSE: Microsatellite instability (MSI) occurs as a result of sliding in the DNA sequences from shortening or elongation of the repeat zones of DNA during replication. Such abnormalities can normally be corrected by the enzymes coded by the DNA mismatch repair (MMR) genes. Therefore, detection of MSI is considered to be a sign of disorder of the MMR genes and is interpreted as a replication error phenotype. PATIENTS AND METHODS: We evaluated the MSI in 5 different loci in the 14q32 region of immunoglobulin heavy chain IgH gene in 26 newly diagnosed patients with multiple myeloma (MM). RESULTS: Fifty-four percent of the patients disclosed MSI and at least 1 locus but no significant association of MSI was found between different clinical stages and the MM subtype. MSI was not found in 5 light-chain myeloma patients. CONCLUSION: Although our case number is small, probably the genomic instability in heavy-chain MM may be a common finding and probably plays a critical role in the MM pathogenesis.

Posttransplant lymphoma in renal and heart allograft recipients: a single center experience.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation, with a reported incidence between 0.8% to 32%. Herein we retrospectively analyzed the patients who diagnosed as PTLD in Akdeniz University. Within the 782 (773 renal and 9 heart) transplant recipients six patients were diagnosed as PTLD (diffuse large B-cell lymphoma). Five of them had renal, one had cardiac transplantation. Three patients were diagnosed within the first year of transplantation. Five patients had abdominal disease one had central nervous system involvement. All patients had positive Epstein-Barr virus (EBV) and cytomegalovirus (CMV) IgG at the time of diagnose. EBV-DNA with polymerase chain reaction (PCR) was found to be negative in five patients. Only one patient was survived after the diagnosis of PTLD. In conclusion, even with treatment the mortality rate is high in patients with PTLD. In order to decrease the incidence of PTLD and related mortality, the risk factors should be evaluated with multicenter studies.

Effect of iron deficiency anemia on the levels of hemoglobin A1c in nondiabetic patients.

The major form of glycohemoglobin is hemoglobin A1c (HbA1c). The HbA1c fraction is abnormally elevated in chronic hyperglycemic diabetic patients and correlates positively with glycemic control. Previous studies suggest that iron deficiency anemia (IDA) affects the levels of HbA1c. The aim of this study was to determine the effect of IDA on HbA1c levels in nondiabetic patients. The population studied consisted of 50 patients (30 women, 20 men, mean age 35.7 +/- 11.9 years) with IDA and 50 healthy subjects that were matched for age and sex. Patients who had glucose tolerance abnormalities (impaired glucose tolerance or diabetes mellitus), hemoglobinopathies, hemolytic anemia, chronic alcohol ingestion and chronic renal failure were excluded from the study. Hematologic investigations, fasting and postprandial glucose and HbA1c levels were measured in all subjects before iron therapy. All patients with IDA were treated with iron 100 mg/day for 3 months. We repeated the laboratory investigation after iron therapy. Before iron treatment, the mean HbA1c (7.4 +/- 0.8%) level in patients with IDA was higher than in a healthy group (5.9% +/- 0.5) (p < 0.001). In patients with IDA, HbA1c decreased significantly after iron treatment from a mean of 7.4% +/- 0.8 to 6.2% +/- 0.6 (p < 0.001). Iron deficiency must be corrected before any diagnostic or therapeutic decision is made based on HbA1c.

The effect of pentoxifylline on haemolysis in patients with double cardiac prosthetic valves.

OBJECTIVE: Intravascular haemolysis frequently occurs in patients with mechanical heart valve prostheses. In this prospective study, we investigated whether pentoxifylline (PTX) has an effect on haemolysis following prosthetic valvular replacement in 40 patients who underwent double valve (mitral and aortic) replacement. METHODS AND RESULTS: The patients were randomly assigned to two groups as control (n = 20) and PTX group (n = 20). PTX was given in a daily oral dose of 1200 mg (3 times 400 mg) for 120 days. Laboratory tests for evidence of haemolysis namely, haemoglobin (Hb), haematocrit (Hct), plasma total bilirubin, indirect bilirubin and haptoglobin levels, corrected reticulocyte percent and serum lactic dehydrogenase activity (SLDH) were performed before and after the PTX treatment. PTX treatment caused significant increases in Hb, Htc, and haptoglobin levels (P < 0.05, P < 0.05 and P < 0.01, respectively). Additionally, there were significant decreases in SLDH, total and indirect bilirubin levels, and corrected reticulocyte percent in patients receiving PTX as compared with their respective control values (P < 0.01, for all). PTX treatment caused a significant improvement, to different extents, in signs of haemolysis in 60% of the patients. On the other hand, the response rate was 5% in the placebo-treated control group (P < 0.05). CONCLUSIONS: These findings suggest that PTX may be an effective agent in the management of haemolysis in patients with prosthetic heart valves.

Iron deficiency anemia in the elderly: prevalence and endoscopic evaluation of the gastrointestinal tract in outpatients.

Iron deficiency anemia (IDA), mostly due to chronic occult bleeding from the gastrointestinal tract, is a common problem in the elderly. This study aimed to determine the prevalence of IDA in the elderly and to investigate the gastrointestinal tract in elderly patients with IDA. 1,388 patients over 65 years were prospectively evaluated for IDA in our outpatient clinic. IDA was defined if decreased hemoglobin concentrations (<13 g/dl for men and <12 g/dl for women) were associated with low serum ferritin levels (<15 ng/ml in men and <9 ng/ml in women). We evaluated the gastrointestinal system of all patients with IDA by upper gastrointestinal endoscopy and colonoscopy regardless of fecal occult blood loss. The prevalence of anemia was found to be 25% (n = 347) in our study population, and 30.5% (n = 106) of these patients with anemia had iron deficiency. Upper gastrointestinal endoscopy and colonoscopy were performed in 96 patients with IDA. Fifty-eight upper gastrointestinal system lesions (55 patients, 57.3%) and 27 colonic lesions (26 patients, 27.1%) were detected. We diagnosed gastrointestinal malignancy in 15 (15.6%) elderly patients with IDA (8 colon, 1 esophageal and 6 gastric cancers). IDA is a common problem in elderly patients; consequently, before iron replacement therapy, patients should be thoroughly investigated regarding a possible association with gastrointestinal malignancy.

Bacteremia caused by Brevibacterium species in a patient with chronic lymphocytic leukemia.

We report a case of bacteremia caused by Brevibacterium species which is one of the coryneform bacteria, in a patient with chronic lymphocytic leukemia. We conclude that, if a coryneform bacteria is isolated from sterile body sites, it must be carefully evaluated, and especially in immunocompromised patients, Brevibacterium species should be considered as potential pathogens.