Efficacy and safety of high-dose intravenous iron as the first-choice therapy in outpatients with severe iron deficiency anemia.

BACKGROUND: Asymptomatic severe iron deficiency anemia is a common finding in subjects admitted to the outpatient anemia clinic. Although the condition can be easily be reversed with intravenous iron (IVI) therapy and several guidelines have suggested a restrictive threshold for using transfusion in hemodynamically stable patients, transfusion is often the rule in clinical practice. This study describes clinical practice results of IVI therapy without transfusion. STUDY DESIGN AND METHODS: In this multicenter retrospective observational study, data of severely anemic outpatients treated only with high-dose IVI with ferric carboxymaltose were collected. Inclusion criteria were hemoglobin (Hb) level of less than 7.0 g/dL and ferritin level of less than 30 ng/mL or mean corpuscular volume of less than 75 fL. RESULTS: Overall, 303 patients referred to the anemia clinic mainly from primary health care centers (46.2%) or the emergency department (28.7%) met the inclusion criteria. Median (interquartile range [IQR]) age was 47 (37-62) years and 84.5% were female. The median (IQR) Hb concentration at first visit was 6.5 (6.1-6.8) g/dL, 64 patients (21.1%) presented with a Hb level of less than 6.0 g/dL at diagnosis, and 11 of them (3.6%) had extreme anemia (Hb ≤ 5 g/dL). Gynecologic and gastroenteric bleeding were the main cause. After a mean IV administration of 1500 mg of iron, the Hb increased by a median of 5.7 g/dL. Thirteen patients experienced only mild side effects. CONCLUSIONS: In chronic very severe sideropenic anemias, third-generation IVI is effective and safe for quick correction and avoidance of red blood cell transfusion. These results suggest that more specific guidelines for this clinical setting are warranted.

Intravenous ferric carboxymaltose is effective and safe in patients with inflammatory rheumatic diseases.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of ferric carboxymaltose in rheumatic patients with iron deficiency anaemia. MATERIALS AND METHODS: The study retrospectively evaluated a cohort of 34 patients with iron deficiency anaemia affected by inflammatory rheumatic diseases that are refractory or intolerant to oral iron therapy. They were treated with ferric carboxymaltose for a total of 56 cycles of treatment. The primary end point was to evaluate the increase of haemoglobin after ferric carboxymaltose treatment. The secondary end point was safety, including the occurrence of disease flare. RESULTS: Median age of the cohort was 60 years (range 31-91 years), with a male/female ratio of 4/30. Nine (26.5%) were affected by rheumatoid arthritis, 10 (29.4%) by spondyloarthritis, and 15 (44.1%) by other autoimmune connective tissue diseases. Median time from diagnosis was 7 years (IQR 2-12). At time of treatment (T0), median haemoglobin was 9.3 g/dL (IQR 8.2-10.3), transferrin saturation 6.2% (IQR 3.8-9.8), and ferritin 8.5 ng/mL (IQR 6.0-12.8). Median ferric carboxymaltose dose was 1,000 mg. At 6 weeks from T0, median haemoglobin was 12.3 g/dL (IQR 11.6-13.3), with a mean increase of 3.0 g/dL (p<0.01). Twelve (35.3%) patients needed re-treatment with ferric carboxymaltose for recurrence of iron deficiency anaemia. Four (4.3%) patients developed mild grade side effects. One suspected flare reaction has been observed. DISCUSSION: In patients affected by inflammatory rheumatic diseases, ferric carboxymaltose is safe and effective in correcting iron deficiency anaemia.

Effect of a liberal versus a restrictive pre-donation blood pressure policy on whole-blood donor adverse reactions.

BACKGROUND AND OBJECTIVES: The role of pre-donation blood pressure (BP) as independent contributor to post-donation vasovagal reactions (VVRs) is still debated. Differences between a liberal (i.e., inclusion of hypotensive donors) and a restrictive policy (i.e., not accepting hypotensive donors) should be investigated. This study aims to investigate the consequences of a liberal policy in development of VVRs after whole-blood donations. MATERIALS AND METHODS: We compared the incidence of VVRs between 2015 (restrictive policy) and 2016 (liberal policy) and the associated risk factors. We evaluated respectively 22 789 vs. 21 676 blood donations obtained from 18 001 blood donors (12 501 donated in both years). RESULTS: Comparing the results we obtained between 2015 and 2016, donations showed an overlap of the cohorts. Two hundred fifteen VVRs (incidence rate 0·48%) were observed, 104 (0·46%) of which in 2015, and 111 (0·51%) in 2016. A preliminary univariate analysis showed that donors with systolic BP <110 mm Hg had a two-fold risk of VVRs compared to normotensive donors (VVR/donation rate of 0·99% vs. 0·46%; P = 0·001). The subsequent multivariable logistic regression model showed that VVRs were highly associated with weight, site of collection, age and number of donations, excluding a role for systolic and diastolic BP. CONCLUSION: A liberal pre-donation BP policy seems to be safe for blood donors. Our analysis confirms that older donors with higher body-weight who already had donated blood are unlikely to experience VVRs.

Prognostic value of PET/CT in patients with lymphoma treated with autologous stem cell transplantation for relapsed/refractory or high risk disease.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT scan) has increasingly been used for management of lymphoma, however few and conflicting data have been provided in the setting of high dose therapy with autologous stem cell transplantation (ASCT) so far. METHODS: We retrospectively evaluated the outcome of 47 NHL patients who underwent ASCT for relapsed/refractory disease or high risk disease or partial response after first line treatment, with the aim of testing sensitivity, specificity, positive and negative prognostic value of PET/CT performed before and after ASCT. RESULTS: In our experience pre ASCT-PET/CT predicts outcome of non-Hodgkin's lymphoma patients with chemosensitive relapse, whereas post ASCT-PET showed a better prognostic value for relapsed disease. CONCLUSIONS: Results of our study, if confirmed by studies on a larger scale, could significantly contribute to design future trials and optimize the management of lymphoma patients.

Validity and reliability of serologic immunophenotyping of multiple blood group systems by ORTHO Sera with fully automated procedure.

CONCLUSIONS: The increase of immunization against blood group antigens has reinforced the need for automated extensive blood typing. The aim of this study was to assess both the validity and reliability of red blood cell (RBC) automated agglutination technology in testing for antigens of Kidd (Jk), Duffy (Fy), and MNS (Ss) blood systems. ORTHO Sera (Ortho Clinical Diagnostics, Raritan, NJ) anti-Jka, anti-Jkb, Anti-Fya, anti-Fyb, anti-S, and anti-s reagents were each tested on RBC samples previously typed. Replicates were performed on three separate testing sessions with three consecutive repetitions within each session, thus obtaining 486 test results. Accuracy was assessed by aggregate analysis of sensitivity, specificity, and area under the receiver operating characteristics curve (AUC). Reliability was estimated by a cross-classified mixed-effect logistic model. All reagents tested yielded optimal accuracy (100% for sensitivity and specificity, and 1.00 for AUC), except for anti-S, for which performance was slightly lower (98%, 100%, and 0.99, respectively), owing to misclassification of one sample in a single replicate. Anomalous automated measurements were recorded in 38 of 486 tests (7.8%), which then needed additional manual interpretation. Different sessions and samples were the major contributors to measurement failures (38% and 18%, separately). Order of repetitions and antigen specificity across replicates did not contribute to the risk of failures, although weak evidence of enhanced risk was observed with Jk testing. Automated RBC typing with ORTHO Sera reagents against antigens in the Kidd, Duffy, and MNS blood group systems displayed nearly 100 percent accuracy. However, a sizable number of replicates needed additional ad hoc interpretation, thus suggesting that the reliability could still be improved. Automated agglutination technology represents a viable option for phenotyping large volumes of samples.

Endothelin-1 receptor blockade as new possible therapeutic approach in multiple myeloma.

New effective treatments are needed to improve outcomes for multiple myeloma (MM) patients. Receptors with restricted expression on plasma cells (PCs) represent attractive new therapeutic targets. The endothelin-1 (EDN1) axis, consisting of EDN1 acting through EDN-receptor A (EDNRA) and B (EDNRB), was previously shown to be overexpressed in several tumours, including MM. However, there is incomplete understanding of how EDN1 axis regulates MM growth and response to therapy. Besides EDNRA, the majority of MM cell lines and primary malignant PCs express high levels of EDNRB and release EDN1. Similarly, bone-marrow microenvironment cells also secrete EDN1. Investigating the extent of epigenetic dysregulation of EDNRB gene in MM, we found that hypermethylation of EDNRB promoter and subsequent down-regulation of EDNRB gene was observed in PCs or B lymphocytes from healthy donors compared to EDNRB-expressing malignant PCs. Pharmacological blockade with the dual EDN1 receptor antagonist bosentan decreased cell viability and MAPK activation of U266 and RPMI-8226 cells. Interestingly, the combination of bosentan and the proteasome inhibitor bortezomib, currently approved for MM treatment, resulted in synergistic cytotoxic effects. Overall, our data has uncovered EDN1-mediated autocrine and paracrine mechanisms that regulate malignant PCs growth and drug response, and support EDN1 receptors as new therapeutic targets in MM.

Ferric carboxymaltose reduces the number of red blood cell units transfused and allows transfusion independence to be obtained in patients with iron deficiency anemia secondary to gastrointestinal chronic blood loss.

BACKGROUND: The aim of this study was to evaluate the effectiveness of ferric carboxymaltose (FCM) in patients with iron deficiency anemia (IDA) secondary to gastrointestinal chronic blood loss (CBL), who received chronic transfusion support. STUDY DESIGN AND METHODS: We retrospectively evaluated 38 patients with IDA (hemoglobin [Hb] < 10 g/dL and ferritin < 12 ng/mL or transferrin saturation [TSAT] < 16%) refractory or intolerant to oral iron therapy that necessitated transfusion support in the previous 12 months. They were treated with FCM (500-2500 mg). The primary endpoint was to evaluate the reduction of transfusion requirements (red blood cell [RBC] units) after FCM treatment. RESULTS: The median age of the cohort was 78 years, with a male:female ratio of 22:16. Before FCM treatment a median of 6 RBC units had been transfused. At the treatment (T0) the median value of Hb was 8.7 g/dL, the TSAT 6%, and ferritin 12 ng/mL. The median FCM dose was 1000 mg. At 5 weeks from T0 the median Hb level was 11 g/dL, with a median increase of 2.4 g/dL. With a median follow-up of 326 days, the median transfusion requirement was 0 RBC units, significantly lower than before T0 (p < 0.001). Overall 17 patients still necessitated transfusion support. Twenty-three patients needed retreatment with FCM for recurrence of IDA: 10 of them obtained a response again. The percentage of transfusion-independent patients at median follow-up was equal to 52%. CONCLUSION: In patients with IDA secondary to CBL, FCM significantly reduces the need of transfusions and achieves transfusion independence in half of the cases.

Single-donor platelet apheresis: observational comparison of the new Haemonetics Universal Platelet protocol with the previous Concentrated Single Donor Platelet protocol.

BACKGROUND: The Haemonetics MCS(®)+ cell separator is a device dedicated to the collection of leucoreduced single-donor platelets. The new Universal Platelet protocol has been introduced to improve the efficiency of apheresis and increase flexibility in the collection of leucoreduced platelets in combination with red blood cells and plasma. In this study we compared its performance with that of the previous Concentrated Single Donor Platelet protocol. MATERIALS AND METHODS: This observational study had a within-subject design and involved 135 donors who underwent plateletapheresis with both protocols. The primary end-point was collection efficiency; secondary end-points were other performance indices, such as procedure time and collection rate. A satisfaction questionnaire was also administered to the 135 donors to evaluate opinions on duration, comfort and side-effects of donations with the two protocols. For each parameter of interest, we tested the difference between the two protocols within donors, using a one-sample t-test or exact McNemar's test as appropriate. RESULTS: The collection efficiency of the Universal Platelet protocol was significantly higher than that of the Concentrated Single Donor Platelet protocol (58% vs 47%; p<0.0001). The Universal Platelet Protocol collected more platelets in less time, leading to a higher collection rate (6.5 vs 5.0×10(9)/min; p<0.0001). In general, donors found apheresis with the Universal Platelet protocol of equal duration or faster, of similar or greater comfort and with an equal number or fewer side effects, compared with the Concentrated Single Donor Platelet protocol. DISCUSSION: Our study endorses the use of the new Universal Platelet protocol in daily transfusion practice since it substantially improves collection efficiency in leucoreduced platelet procedures compared with the Concentrated Single Donor Platelet protocol. This technical improvement seems to be accompanied by equal or greater comfort for the donor.