Lexaptepid pegol (LP) is a PEGylated L-stereoisomer RNA aptamer that binds and neutralizes hepcidin. Hepcidin, a 25 amino acid peptide induced by inflammatory stimuli is a pivotal regulator of iron resorption and iron release from intracellular stores, which are severely impaired in anemia of chronic disease. Disturbances in iron metabolism resulting in functional iron deficiency are a key component of anemia of chronic disease which frequently complicates malignant disease. We evaluated the pharmacokinetics, pharmacodynamics, safety and efficacy of hepcidin blockade by LP as sole treatment of anemia of chronic disease in patients with multiple myeloma, low grade Non-, or Hodgkin lymphoma. Twelve patients with functional iron deficiency anemia with the following baseline characteristics, presented as median (range), were enrolled: age 64 years (35-77), Hb 9.6 g/dL (8.0-10.7), serum ferritin 317 µg/L (193-2805), serum iron 29 µg/dL (18-97), TSAT 12% (6-46). LP was injected i.v. at a dose of 1.2 mg/mg, TIW for 4 weeks. Blood counts, serum biochemistry, and iron status were evaluated weekly until two weeks post treatment and at week four after the end of therapy. The primary endpoint was increase in Hb by ≥1 g/dL at any time between start of therapy until 1 week after end of treatment. The study has the clinicaltrials.gov identifier NCT 01691040. Five of the 12 patients reached the target Hb increase of ≥1 g/dL, 3 patients achieved this goal within 2 weeks. Four of the 5 responding patients had hypochromic anemia (MCH 22-26 pg) and moderately increased baseline ferritin levels (200-350 µg/L). Median serum ferritin decreased from 317 to 232 µg/L (p=0.014) in the entire cohort of patients, and from 253 to 203 µg/L in responders (p=n.s). Reticulocyte hemoglobin increased from 22.0 to 25.2 pg (p=0.019) in responding patients, while in non-responders no increase was noted (30.0 to 30.1 pg). Similarly, a trend to increased reticulocyte index was observed in the responding patients (median: 0.9 to 1.3, p=n.s.) only. Soluble transferrin receptor levels (sTFR) showed a trend to decrease in responders (10.6 to 10.3 mg/L, p=n.s.), but remained unchanged in non-responders. Treatment with LP was well tolerated without major adverse reactions. In conclusion, LP induced a significant increase in Hb levels (≥1 g/dL) in 5 of 12 patients. Responding patients showed an increase in red cell and reticulocyte hemoglobin, and decrease in sTFR. These results support the concept of hepcidin inhibition for treatment of cancer associated anemia with functional iron deficiency. Patients with signs of iron deficiency as documented by hypochromic anemia, no excessive increase in ferritin and high sTFR levels showed a higher likelihood to respond to LP. Citation Format: Pencho Georgiev, Mihaela Lazaroiu, Luminita Ocroteala, Janet Grudeva-Popova, Emanuil Gheorghita, Mariana Vasilica, Sanda M Popescu, Andrei Cucuianu, Luciana Summo, Frank Schwoebel, Kai Riecke, Heinz Ludwig. The anti-hepcidin Spiegelmer® Lexaptepid Pegol (NOX-H94) as treatment of anemia of chronic disease in patients with multiple myeloma, low grade lymphoma, and CLL: A phase II pilot study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3847. doi:10.1158/1538-7445.AM2014-3847

We report a case of scleredema of Buschke associated with IgG kappa monoclonal hypergammaglobulinaemia. After myeloma polychemotherapy an improvement in skin involvement was observed and confirmed by means of noninvasive skin elasticity measurements. This suggests a relationship between the two diseases. The bioengineering method used can be useful for early detection and monitoring the skin involvement in patients with this disease association.

Malignancy arises and progresses in tight association with changes in the tumor microenvironment and deregulation of hemostatic system. Cancer induces hemostatic imbalance through production and secretion of procoagulant substances, suppression of anticoagulant mechanisms, endothelial activation, and angiogenic switch. Cancer cells are equipped with certain coagulation signaling receptors such as tissue factor TF and urokinase plasminogen activator receptor uPAR . Tissue factor as major initiator of coagulation, TF is considered the main cause for hypercoagulability in cancer. Constitutive TF expression by cancer cells is a hallmark of malignancy rendering tumors proangiogenic and prometastatic. TF fosters metastasis through coagulation-dependent pathways leading to fibrin deposition in the evolving premetastatic niche. TF has been identified as an independent predictor for metastatic development and adverse prognosis. uPAR Tissue overexpression of uPAR is demonstrated in almost all human cancers and is associated with advanced disease. Increased uPAR expression is driven by molecular events involving K-ras and SRC oncogenes. Transactivation of these receptors, mediated by binding to hemostatic proteins, activates intracellular signaling pathways, modulates gene expression and facilitates processes of tumor initiation, epithelial-to-mesenchymal transition, anoikis, and metastasis. By manipulating hemostatic processes, tumor induces tolerant host environment necessary for evasion of defense attacks, survival, and progression.

The prognostic factors identified in the present study can be easily applied in the clinical practice and may be used as a basis for creating mathematical prognostic models.

Dapsone is a drug commonly used in the treatment of leprosy. In Europe it is rarely prescribed, mostly for the treatment of skin diseases such as dermatitis herpetiformis. Poisoning with dapsone is rare and reports of such cases are of interest for toxicological practice. We describe the only acute dapsone poisoning in a caseload series of 21,000 intoxications treated in the Clinical Toxicology Clinic at St George University Hospital in Plovdiv, Bulgaria between 1999 and 2013. We report on a 36-year-old woman who attempted deliberate self-poisoning with an ingestion of approximately 4.5 g of dapsone and 0.3 g of olanzapine. On admission, the patient was in a state of severe intoxication and comatose. On admission to hospital 9 hours after the ingestion, the methemoglobin level was 51.7%. The patient recovered 8 days later. She received complex treatment including intubation, ventilation, repeated gastric lavage, hemodialysis, blood exchange transfusion and antidote treatment with methylene blue. She was discharged in good clinical condition with minimal organ damage such as mild toxic hepatitis.