Paraproteinaemia in Primary Cutaneous Marginal Zone Lymphoma.

Primary cutaneous marginal zone lymphomas (PCMZL) frequently exhibit lymphoplasmacytoid/plasmacytic differentiation, implying the capacity to produce monoclonal immunoglobulins. As these paraproteins are secreted, and thus are measurable in blood and urine, they may correlate with disease burden and serve as tumour markers reflecting therapeutic response. This study retrospectively analysed the records of 23 patients with PCMZL. During treatment and follow-up, laboratory tests, including full blood count, lactate dehydrogenase, serum protein electrophoresis and turbidimetric analyses, were conducted. Thirty-nine percent of cases showed a suspicious serum protein electrophoresis in terms of paraproteinaemia. In 44% of cases the heavy and light chain restriction in tissue samples correlated with serological findings. Altogether, 89% of the PCMZL patients with paraproteinaemia eventually experienced a relapse, in contrast to 62% of the group without paraproteinaemia. This study analysed the incidence and clinical implications of paraproteinaemia in patients with PCMZL. A clear correlation was found between paraproteinaemia, tumour relapse and therapeutic intervention.

Influence of the amount of co-infused amino acids on post-therapeutic potassium levels in peptide receptor radionuclide therapy.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is routinely used for advanced or metastasized neuroendocrine tumours (NET). To prevent nephrotoxicity, positively charged amino acids (AA) are co-infused. The aim of this study was to correlate the risk for therapy-related hyperkalaemia with the total amount of AA infused. METHODS: Twenty-two patients undergoing PRRT with standard activities of (177)Lu-DOTATATE/-TOC were monitored during two following treatment cycles with co-infusion of 75 and 50 g of AA (l-arginine and l-lysine), respectively. Mean serum levels of potassium and other parameters (glomerular filtration rate [GFR], creatinine, blood urea nitrogen [BUN], phosphate, chloride, lactate dehydrogenase) prior to, 4 h and 24 h after AA infusion were compared. RESULTS: Self-limiting hyperkalaemia (>5.0 mmol/l) resolving after 24 h occurred in 91% (20/22) of patients in both protocols. Potassium levels, BUN, creatinine, GFR, phosphate, chloride and LDH showed a similar range at 4 h after co-infusion of 75 or 50 g of AA, respectively (p?>?0.05). Only GFR and creatinine levels at 24 h varied significantly between the two co-infusion protocols (p?

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0). METHODS: In 38 patients, standard activity of (177)Lu-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated. RESULTS: At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK. Increases in K(+) were significantly correlated with decreases in phosphate (r = -0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37). Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%). CONCLUSIONS: A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying 'high-risk' patients prone to PRRT.

Force field evolution during human blood platelet activation.

Contraction at the cellular level is vital for living organisms. The most prominent type of contractile cells are heart muscle cells, a less-well-known example is blood platelets. Blood platelets activate and interlink at injured blood vessel sites, finally contracting to form a compact blood clot. They are ideal model cells to study the mechanisms of cellular contraction, as they are simple, having no nucleus, and their activation can be triggered and synchronized by the addition of thrombin. We have studied contraction using human blood platelets, employing traction force microscopy, a single-cell technique that enables time-resolved measurements of cellular forces on soft substrates with elasticities in the physiological range (∼4 kPa). We found that platelet contraction reaches a steady state after 25 min with total forces of ∼34 nN. These forces are considerably larger than what was previously reported for platelets in aggregates, demonstrating the importance of a single-cell approach for studies of platelet contraction. Compared with other contractile cells, we find that platelets are unique, because force fields are nearly isotropic, with forces pointing toward the center of the cell area.

Anticoagulation in large-volume leukapheresis: comparison between citrate- versus heparin-based anticoagulation on safety and CD34 (+) cell collection efficiency.

BACKGROUND AIMS: Little is known of the effect of anticoagulation on peripheral blood progenitor cell (PBPC) harvest during large-volume leukapheresis (LVL). Because of the interaction of heparin with stromal cell-derived factor (SDF)-1α, it has been proposed that a heparin-based anticoagulation may result in an increased PBPC collection efficiency compared with standard citrate-based anticoagulation. METHODS: We conducted a prospective randomized trial to address the effect of both anticoagulation regimes on safety, subjective comfort and CD34 (+) collection efficiency in 90 adult patients undergoing standardized LVL. Anticoagulation consisted of either citrate (group C) or a combination of heparin and low-dose citrate (group H). RESULTS: The overall incidence of adverse reactions (AR) during LVL was 17%. AR consisted only of citrate-related AR; no bleeding complications were observed. Determination of parameters of the acid-base balance revealed a higher frequency of metabolic alkalosis in group C. Analysis of serum SDF-1α revealed no differences in SDF-1α plasma levels. There were no differences in the CD34 (+) cell collection efficiency, resulting in the harvest of equal CD34 (+) cell yields independent of the anticoagulation used. CONCLUSIONS: Our data show no clinical relevant effect of a heparin containing anticoagulation in terms of an increased overall CD34 (+) cell collection during LVL, although this regime shows some benefits in terms of the incidence and subjective tolerance towards AR. Based on our results the decision between a citrate- and heparin-substituted anticoagulation for LVL should be driven by patient-related factors, and should concern potential contraindications of both methods.

Cryopreservation of cellular products in a closed-bag system with an incorporated dimethyl sulfoxide-resistant sterile filter outside of cleanroom facilities.

BACKGROUND: Manipulations, for example, cryopreservation, of cellular therapeutics carried out in an open system must be performed in a class A environment with surrounding class B environment. To avoid cleanroom facilities, a new closed-bag system with an incorporated dimethyl sulfoxide-resistant sterile filter for cryopreservation of cellular products was evaluated at two different centers. STUDY DESIGN AND METHODS: A total of 44 different products (22 buffy coats [BCs] and 22 leukapheresis [LK] products) were split and cryopreserved in parallel in cleanroom facilities (Method I) and with the closed system on the bench of a "normal" laboratory (Method II). Viability analyzed by 7-aminoactinomycin D staining and flow cytometric analysis and sterility of the products were analyzed. RESULTS: Independent of the cellular source (BC or LK), the median viability of CD45+ cells decreased significantly (p < 0.01) during cryopreservation: namely, in BCs, -15.8 percent with both methods, and in LK products, -5.4 percent with Method I and -4.8 percent with Method II, respectively. CD3+ as well as CD14+ cells exhibited a similar pattern and were also found significantly (p < 0.01) diminished after thawing independent of the handling system. For CD19+ cells, the small decrease of viability was only for the BC group significant (p = 0.027) when the cells had been processed with Method I. No bacterial contamination was detected neither in fresh products nor in products after cryopreservation. CONCLUSION: The closed system for cryopreservation of cellular products appears to be equivalent to cleanroom-based methods regarding cellular integrity and sterility when appropriate quality of sterile filters is assured.