Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG)

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real-world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma.     

Biosimilar filgrastim (leucostim®) have similar efficacy in steady-state hematopoietic progenitor cell mobilization compared to original filgrastim (neupogen®) and lenograstim (granocyte®): A retrospective multicenter study

Biosimilar filgrastim (Leucostim^®) was shown to be similar in terms of efficacy and safety in hematopoietic progenitor cell mobilization (HPCM) compared to originator filgrastim (Neupogen^®) and lenograstim (Granocyte^®) in healthy donors and chemomobilization settings. Here we report our retrospective experience with Leucostim^® (n: 43) compared to Neupogen^® (n: 71) and Granocyte^® (n: 32) in steady-state mobilization of patients presenting with Hodgkin lymphoma, non-Hodgkin lymphoma and multiple myeloma. The median age of patients on Leucostim^® (56) arm was significantly higher compared to patients who received Neupogen^® (50) and Granocyte^® (49) (p: 0.039). Patients who underwent HPCM with Leucostim^® received less chemotherapy lines (p: 0.026) and courses (p: 0.046) compared to others. Otherwise the study cohort was homogenous in terms of gender, primary diagnosis and various risk factors for mobilization failure. Mobilization failure was defined as failure to achieve a minimum threshold (10/μL) for peripheral blood CD34⁺ cell concentration to initiate leukapheresis or 0.5 × 10⁶/kg, 0.8 × 10⁶/kg and 2 × 10⁶/kg CD34⁺ cells in first, second and fourth days of apheresis, respectively. The study groups were similar in terms of median number of CD34⁺ progenitor cell yield ( × 10⁶/kg) (Neupogen^®: 6.18, Granocyte^®: 6.2 and Leucostim^®: 6.2) (p: 0.959) and median number of leukapheresis sessions (p: 0.615). The treatment arms were also similar in terms of mobilization failure (Neupogen^® 11.3% ? Granocyte^® 21.9% ? Leucostim^® 16.3%; p: 0.366). No patient experienced any severe adverse effect during HPCM. Leucostim^® is equally effective and safe in HPCM compared to originator G-CSF (Neupogen^®) and lenograstim (Granocyte^®) in steady-state HPCM setting.     

Overexpression of cyclooxygenase-2 in multiple myeloma: association with reduced survival

Cyclooxygenases (COX) are key enzymes in the conversion of arachidonic acid to prostaglandins. Several studies have shown a relation between angiogenesis and COX-2 expression. Elevated expression of cyclooxygenase-2 (COX-2), however, has not been reported in multiple myeloma (MM) in the literature. The aim of this study is to investigate COX-2 expression in MM as well as its correlation with prognostic factors and estimated survival rates. Immunohistochemical staining of the paraffin-embedded bone marrow biopsy tissues (n = 51) was performed using isoform-specific COX-2 polyclonal antisera (Santa Cruz Biotechnology, Santa Cruz, CA). Results were correlated with recognized clinical parameters, which were retrospectively obtained from patients' files. There were 15, 19, and 17 bone marrow biopsy specimens with negative, weak-moderate, and strong COX-2 immunostaining, respectively. According to univariate analysis, beta2-microglobulin, age, stage, COX-2 expression, and serum lactate dehydrogenase levels were significant prognostic factors for survival in patients with multiple myeloma. COX-2 expression, age, and serum lactate dehydrogenase levels (greater than 1x normal level) were significant prognostic factors by multivariate analysis. Kaplan-Meier overall survival estimate of those patients with negative or weak-moderate COX-2 immunoreactivity in myeloma cells was significantly better than that of patients with strong COX-2 immunoreactivity (log-rank chi(2) = 21,43, P < 0.001). COX-2 overexpression was associated with reduced estimated survival. Poor prognostic factors such as LDH, age, and beta2-microglobulin were also correlated with COX-2 expression. Potent, specific COX-2 inhibitors showing evident antiangiogenic and antitumor effects on cancers could provide new therapeutic strategies in the treatment of MM.     

Intravenous gamma globulin is effective as an urgent treatment in Brucella-induced severe thrombocytopenic purpura

Severe thrombocytopenia is a rare hematologic manifestation of brucellosis, which can occasionally be associated with bleeding into the skin and from mucosal sites. Prompt recognition of this brucellosis complication and aggressive therapy is vital because the mortality rate associated with bleeding into the central nervous system is high. We report a case of a patient infected with Brucella melitensis who was admitted with a severe case of thrombocytopenic purpura. The patient responded well to intravenous gamma globulin (IVIg) treatment with platelet recovery within 2-3 days. For cases of Brucella-induced thrombocytopenic purpura, IVIg may be administered as an urgent therapy until the microbial therapy takes effect.     

Replacement of the Ascending Aorta for Severe Atherosclerosis During Coronary Artery Bypass Surgery

Abstract Background and Aim : In the present study, we investigated the benefit of ascending aorta replacement in patients with severe aortic atherosclerosis who undergo coronary artery bypass surgery (CABG). Methods : From January 2001 to April 2011, 3842 patients underwent CABG and in 36 of these patients (31 male, 5 female) the ascending aorta was replaced due to severe atherosclerosis. Total circulatory arrest was used in 22 patients (61%). The patients were followed for 69 ± 36 months (1–133 months) and compared to a control group of patients. The control group consisted of patients who underwent CABG with or without a concomitant procedure (n = 3806). Results : For the study group, the mean additive and logistic Euroscores of the patients were nine and 20, respectively. One stroke (2.8%) was observed and this patient died in the early postoperative period. There were a total of four confirmed deaths (12%) at any time point over the length of the follow‐up among the patients who were discharged from the hospital. Two of them died of malignancy (lung and gastric tumors) and the other two from cardiac reasons. No patients had a stroke during follow‐up. For the control group the mean age was 61 ± 1, the stroke rate was 0.6%, and the mortality rate was 0.96%, and the mean logistic and additive Euroscores were 3.7 ± 4.4, and 3.5 ± 2.5, respectively. Conclusions : Replacement of highly calcified ascending aortas during CABG can be safely performed in selected patients with good long‐term outcomes. (J Card Surg 2012;27:538‐542)     

Therapeutic plasma exchange in patients with neurological diseases: Multicenter retrospective analysis

Therapeutic plasma exchange (TPE), is a procedure, changing pathologic substances in the plasma of patients with replacement fluid. TPE has an increasing list of indications in recent years such as neurological, connective tissue, hematological, nephrological, endocrinological and metabolic disorders. We report our multicenter data about therapeutic plasma exchange in patients with neurological diseases. Six University Hospitals’ aphaeresis units medical records about neurologic diseases were reviewed retrospectively. Hundred and fifteen patients and 771 TPE sessions from six aphaeresis units’ were included to this study. Of the 115 patients, 53 (46%) were men and 62 (54%) were women. The median age was 50 (range: 5–85) years. Of these patients 58.3% were Guillain–Barre syndrome (GBS), 17.4% were acute disseminated encephalomyelitis (ADEM), 10.4% were chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 7% were multiple sclerosis, 6.1% were myasthenia gravis (MG) and 0.9% were Wilson disease (WD). The median number of TPE sessions per patient was 5 (range 1–72). Human albumin was used as a replacement fluid in 66% and fresh frozen plasma was used in 34% of cases. TPE was done through central venous catheters in 66%, and peripheral venous access in 34% of patients. Some complications were seen in patients (18.3%) during TPE sessions. These complications were, complications related to catheter placement procedure (8.7%), hypotension (3.5%), hypocalcaemia (3.5%) and allergic reactions (1.7%). The complication ratios were 2.7% in total 771 TPE procedures. TPE procedure was terminated in 6% of sessions depending on these complications. Overall responses to TPE were noted in 89.5% of patients.In conclusion; Therapeutic plasma exchange is an effective treatment option in several neurologic diseases.     

Effects of single aortic clamping versus partial aortic clamping techniques on post-operative stroke during coronary artery bypass surgery

Background

The aim of this study was to compare the effects of single-clamping and partial-clamping techniques on postoperative stroke during coronary artery bypass surgery.

Methods

Between December 2008 and December 2012, 2 000 patients who underwent coronary artery bypass grafting in two hospitals were analysed. Post-operative neurological complications were analysed retrospectively in these patients. The cases were divided into two groups: in group 1, 1 500 patients were analysed, in whom proximal anastomosis was performed with partial clamping in a beating heart (n = 1 500, 846 male, 654 female; mean age 63.25 ± 5.72 years; range 43–78 years). In group 2, 500 patients were analysed, in whom proximal anastomosis had been performed by other surgical teams in another hospital, with cross clamping in a resting heart with cardioplegia (n = 500, 296 male, 214 female; mean age 64.83 ± 8.12 years; range 41–81 years). During 30 days post-operatively, neurological deficits, stroke incidence and the relationship of the clinical situation to mortality were analysed.

Results

For both groups, patients were similar in terms of patient characteristics. In group 2, cross-clamp duration and perfusion time were longer; however, time of hospital stay was similar in the two groups. Post-operative stroke was seen in 26 patients in group 1 (1.73%) and in nine in group 2 (1.8%). The difference between the two groups was not statistically significant (p = 0.92). All stroke patients were over the age of 55 years. Seven of the stroke patients died (21.1%). In total, 31 patients died because of multiple organ failure in the postoperative 30 days (group 1: 1.6%; group 2: 1.4%) (p = 0.91). Smoking, diabetes mellitus, hypertension, atrial fibrillation, peripheral vascular disease and hypercholesterolaemia were found to be factors that affected stroke development. Mean duration of hospital stay was 5.1 ± 2.8 days in group 1 and 4.9 ± 3.6 days in group 2 and the difference between the two groups was not statistically significant (p = 0.46).

Conclusion

In patients without plaques in the aorta, performing partial clamping did not increase stroke incidence.     

Particulate air pollution and respiratory disease in Anchorage, Alaska.

This paper examines the associations between average daily particulate matter less than 10 microns in diameter (PM10) and temperature with daily outpatient visits for respiratory disease including asthma, bronchitis, and upper respiratory illness in Anchorage, Alaska, where there are few industrial sources of air pollution. In Anchorage, PM10 is composed primarily of earth crustal material and volcanic ash. Carbon monoxide is measured only during the winter months. The number of outpatients visits for respiratory diagnoses during the period 1 May 1992 to 1 March 1994 were derived from medical insurance claims for state and municipal employees and their dependents covered by Aetna insurance. The data were filtered to reduce seasonal trends and serial autocorrelation and adjusted for day of the week. The results show that an increase of 10 micrograms/m3 in PM10 resulted in a 3-6% increase in visits for asthma and a 1-3% increase in visits for upper respiratory diseases. Winter CO concentrations were significantly associated with bronchitis and upper respiratory illness, but not with asthma. Winter CO was highly correlated with automobile exhaust emissions. These findings are consistent with the results of previous studies of particulate pollution in other urban areas and provide evidence that the coarse fraction of PM10 may affect the health of working people.     

Bone mineral density and its correlation with clinical and laboratory factors in chronic peritoneal dialysis patients

The aim of this study was to assess the clinical and laboratory correlations of bone mineral density (BMD) measurements among a large population of patients on chronic peritoneal dialysis (PD). This cross-sectional, multicenter study was carried out in 292 PD patients with a mean age of 56 ± 16 years and mean duration of PD 3.1 ± 2.1 years. Altogether, 129 female and 163 male patients from 24 centers in Canada, Greece, and Turkey were included in the study. BMD findings, obtained by dual-energy X-ray absorptiometry (DEXA) and some other major clinical and laboratory indices of bone mineral deposition as well as uremic osteodystrophy were investigated. In the 292 patients included in the study, the mean lumbar spine T-score was −1.04 ± 1.68, the lumbar spine Z-score was −0.31 ± 1.68, the femoral neck T-score was −1.38 ± 1.39, and the femoral neck Z score was −0.66 ± 1.23. According to the WHO criteria based on lumbar spine T-scores, 19.2% of 292 patients were osteoporotic, 36.3% had osteopenia, and 44.4% had lumbar spine T-scores within the normal range. In the femoral neck area, the prevalence of osteoporosis was slightly higher (26%). The prevalence of osteoporosis was 23.3% in female patients and 16.6% in male patients with no statistically significant difference between the sexes. Agreements of lumbar spine and femoral neck T-scores for the diagnosis of osteoporosis were 66.7% and 27.3% and 83.3% for osteopenia and normal BMD values, respectively. Among the clinical and laboratory parameters we investigated in this study, the body mass index (BMI) (P < 0.001), daily urine output, and urea clearance time × dialysis time/volume (Kt/V) (P < 0.05) were statistically significantly positive and Ca × PO₄ had a negative correlation (P < 0.05) with the lumbar spine T scores. Femoral neck T scores were also positively correlated with BMI, daily urine output, and KT/V; and they were negatively correlated with age. Intact parathyroid hormone levels did not correlate with any of the BMD parameters. Femoral neck Z scores were correlated with BMI (P < 0.001), and ionized calcium (P < 0.05) positively and negatively with age, total alkaline phosphatase (P < 0.05), and Ca × P (P < 0.01). The overall prevalence of fractures since the initiation of PD was 10%. Our results indicated that, considering their DEXA-based BMD values, 55% of chronic PD patients have subnormal bone mass—19% within the osteoporotic range and 36% within the osteopenic range. Our findings also indicate that low body weight is the most important risk factor for osteoporosis in chronic PD patients. An insufficient dialysis dose (expressed as KT/V) and older age may also be important risk factors for osteoporosis of PD patients.