TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders

Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10(9)/L. A reduction of platelets to <600 in asymptomatic or <400 x 10(9)/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.     

Serum ferritin: Physiological and methodological studies

Some aspects of normal ferritin physiology have been investigated as well as methodological problems concerning test sample handling etc. No circadian rhythm was found in 11 subjects. The day-to-day variation showed a mean of 9% in 22 subjects, but with considerable individual variation. The ferritin content in erythrocytes was about 0.045 fg/cell, and in leucocytes about 10 fg/cell. Hemolysis of test samples up to a hemoglobin concentration of 3 g/1 in the serum did not significantly change the ferritin concentration. This means that hemolysis of test samples is usually no problem in clinical practice. Serum samples could be stored at ?20°C for a year or freeze-thawed six times without change in ferritin concentration. Heparin- and sodium citrate plasma gave the same results as serum, but EDTA plasma gave 23% (mean) lower values. A moderate amount of alcohol, corresponding to 15 cl of whisky, gave no rise within 56 h in serum ferritin levels in four subjects.     

Serum erythropoietin in cross-country skiers

Serum erythropoietin concentration and hemoglobin concentration were determined during the winter season in 41 male and 31 female well-trained, cross-country skiers. The athletes both lived and trained at low altitude (below 300 m above sea level). No significant differences in serum erythropoietin concentration were seen between male skiers (13.6 +/- 5.0 mU.ml-1), female skiers, (14.9 +/- 5.6 mU.ml-1), and normal controls (12.6 +/- 3.9 mU.ml-1) (mean +/- SD). In 18 of the skiers (12 males and 6 females), a second sample was taken after 2.3 +/- 0.18 months. No significant difference in either serum erythropoietin concentration or hemoglobin concentration was detected between the two samples in this combined group of skiers. The present study indicates that normal serum erythropoietin concentration is to be expected during the winter season at sea level in cross-country skiers living and training at low altitude.     

Oral cryotherapy reduces mucositis and opioid use after myeloablative therapy—a randomized controlled trial

Introduction Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT). Aim The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT. Materials and methods Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts. Results This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids. Conclusion Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT.     

Combination therapy of hydroxycarbamide with anagrelide in patients with essential thrombocythemia in the evaluation of Xagrid? efficacy and long-term safety study

Available information is limited regarding the use of cytoreductive combination therapy in high-risk patients with essential thrombocythemia. This analysis aims to evaluate the clinical relevance and patterns of cytoreductive combination treatment in European high-risk patients with essential thrombocythemia in the Evaluation of Xagrid^® Efficacy and Long-term Safety study. Of 3643 patients, 347 (9.5%) received combination therapy. Data were recorded at each 6-month update. Of 347 patients who received combination therapy, 304 (87.6%) received hydroxycarbamide + anagrelide. Monotherapies received before this combination were hydroxycarbamide (n=167, 54.9%) and anagrelide (n=123, 40.5%). Median weekly doses of hydroxycarbamide and anagrelide were: 7000 and 10.5 mg when used as prior monotherapy; 3500 and 7.0 mg when used as add-on treatment. Overall, median platelet counts were 581×10⁹/L and 411×10⁹/L before and after starting hydroxycarbamide + anagrelide, respectively. In patients with paired data (n=153), the number of patients with platelet counts less than 400×10⁹/L increased from 33 (21.6%) to 74 (48.4%; P<0.0001), and with platelet counts less than 600×10⁹/L, from 82 (53.6%) to 132 (86.3%; P<0.0001). Hydroxycarbamide + anagrelide was discontinued in 158 patients: 76 (48.1%) stopped hydroxycarbamide, 59 (37.3%) stopped anagrelide, 19 (12.0%) stopped both and 4 (2.5%) had another therapy added. The most frequent reasons for discontinuation were intolerance/side-effects, lack of efficacy, and therapeutic strategy. Combination therapy, usually hydroxycarbamide + anagrelide, is used in approximately 10% of all high-risk patients with essential thrombocythemia and may be a useful approach in treating patients for whom monotherapy is unsatisfactory. (Clinicaltrials.gov identifier:{"type":"clinical-trial","attrs":{"text":"NCT00567502","term_id":"NCT00567502"}}NCT00567502)     

Effects of blood transfusions on some hematological variables in endurance athletes

Selected hematological variables (blood hemoglobin concentration [Hb], serum (s-) iron, s-bilirubin, s-ferritin, blood lactate, and s-erythropoietin [Epo]) were analyzed before and for 4 wk after autologous blood transfusions. A group of well-trained (8 male and 4 female) former endurance athletes was phlebotomized and 3-4 months later reinfused with the freezer-stored autologous red blood cells (RBC) from 1350 ml of blood. The [Hb] increased significantly (P less than 0.001 for both sexes) from 146.7 +/- 5.31 and 131.7 +/- 11.20 g. l-1 immediately before reinfusion to maximum values of 163.5 +/- 7.47 and 155.9 +/- 11.43 g.l-1 (mean +/- SD) in males and females, respectively, 2 d after reinfusion. S-iron increased transiently 5 h after reinfusion. S-bilirubin remained unchanged throughout the study. S-ferritin increased gradually (P less than 0.02) from 48 +/- 32.91 mmol.l-1 before reinfusion to a maximum of 80.8 +/- 39.52 mmol.l-1 2 wk after reinfusion. S-[Epo] increased transiently (P less than 0.01) from 8.83 +/- 2.51 (mean +/- SD) to 12.36 +/- 5.64 U.l-1, (mean +/- SD) 5 h after reinfusion. Subsequently, there was a significant marked decrease in s-[Epo] to 5.85 +/- 1.32 U.l-1, (mean +/- SD) 1 d after reinfusion (P less than 000.1, as compared to before reinfusion). Thereafter, s-[Epo] remained low throughout the study. Blood lactate was significantly decreased only the first 2 d after reinfusion (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)