Prevalence and treatment of anemia and secondary iron overload in patients with a myelodysplastic syndrome: Real-world data from a multicenter cohort study.

BACKGROUND: anemia is the most common finding in patients with a myelodysplastic syndrome (MDS). Repetitive red blood cell (RBC) transfusions and disease-related low hepcidin levels induce secondary iron overload. Real-world data on the prevalence and treatment strategies of anemia and secondary iron overload in MDS patients, is limited. METHODS: three years of data on MDS diagnosis, anemia and ferritin management was collected in 230 MDS patients from seven non-academic hospitals in the Netherlands. Descriptive statistics and linear mixed models were used to analyze the data. RESULTS: transfusion dependent (TD) patients (n = 49) needed 1-3 RBC transfusions per month. Serum hemoglobin remained stable in both TD and transfusion-independent (TI) patients over 3 years. In the TD patients, serum ferritin increased 63 pmol/L/month. Overall, 19 (39%) were diagnosed with secondary hemochromatosis, of which 13 (68%) received chelation therapy with a heterogeneous response. CONCLUSIONS: mean hemoglobin remains stable over time in both TD and TI MDS patients. Approximately 40% of TD patients develop secondary hemochromatosis. Treatment and monitoring of secondary hemochromatosis as well as the response on chelation therapy vary substantially.

Clinical and in vitro evaluation of red blood cells collected and stored in a non-DEHP plasticized bag system.

BACKGROUND AND OBJECTIVES: Di-ethyl-hexyl-phthalate (DEHP) is currently the main plasticizer used for whole blood collection systems. However, in Europe, after May 2025, DEHP may no longer be used above 0.1% (w/w) in medical devices. DEHP stabilizes red cell membranes, thereby suppressing haemolysis during storage. Here we compared in vitro quality parameters of red cell concentrates (RCCs) collected and stored in DEHP-, DINCH- or DINCH/BTHC-PVC hybrid blood bags with saline-adenine-glucose-mannitol (SAGM) or phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) storage solution. Last, we performed haemovigilance surveillance for RCC collected in DINCH-PVC and stored in PAGGSM/BTHC-PVC. MATERIALS AND METHODS: In vitro quality parameters of RCC were determined during 42 days of storage. Haemovigilance surveillance was conducted to compare the frequency and type of transfusion reaction. RESULTS: Haemolysis levels were increased in SAGM/BTHC-PVC as compared to SAGM/DEHP-PVC (0.66% ± 0.18% vs. 0.36% ± 0.17%). PAGGSM storage solution was able to adequately suppress haemolysis to levels observed during storage in SAGM/DEHP-PVC, both in BTHC-PVC (0.38% ± 0.12%), and to a slightly lesser extent in DINCH-PVC (0.48% ± 0.17%). A total of 1650 PAGGSM/BTHC-PVC and 5662 SAGM/DEHP-PVC RCC were transfused yielding a transfusion reaction frequency of 0.24% (95% CI 0.0000-0.0048) and 0.44% (95% CI 0.0027-0.0061) respectively. CONCLUSION: The in vitro quality of RCC stored in PAGGSM/BTHC-PVC and SAGM/DEHP-PVC is comparable. There is no indication that transfusion of erythrocytes stored in PAGGSM/BTHC-PVC results in increased transfusion reaction frequency. These initial results provide a basis for further clinical evaluation to narrow down the confidence interval of transfusion reaction frequency.

Risk of thrombosis with thrombopoietin receptor agonists for ITP patients: A systematic review and meta-analysis.

One possible side effect of thrombopoietin receptor agonists in immune thrombocytopenia is thrombosis. Our aim is to systematically review whether patients with ITP that were treated with a TPO-RA have an increased risk for thrombosis as compared to ITP patients without TPO-RA. Patients in the intervention group were required to receive TPO-RA therapy. The primary outcome was the incidence of thromboembolic events. Eleven studies were included in the pooled analysis. More thromboembolic events were noted in the TPO-RA group than in the control group: 25 compared to 4. Ten out of 11 studies showed a relative risk greater than 1. However, none of these individual risk ratios was statistically significant. The meta-analysis showed a RR of 1.82 [95 % CI 0.78-4.24]. Our findings indicate there is a non-significant higher chance of thrombosis in ITP patients with TPO-RA treatments versus ITP patients without TPO-RA treatment.

Prevalence of iron deficiency and red blood cell transfusions in surgical patients.

BACKGROUND AND OBJECTIVES: While iron deficiency (ID) is the most common cause of anaemia, little is known about the prevalence and type of ID in preoperative surgical patients. The aims of the present study were to investigate the prevalence and types of ID in a large cohort of surgical patients, and how these are related to perioperative blood use after correction for confounders such as haemoglobin level. MATERIALS AND METHODS: Data were retrospectively extracted from electronic case records of all patients who underwent elective surgery between September 2016 and November 2017 (n = 2711). Iron parameters, haemoglobin and details of perioperative red cell transfusions were collected. RESULTS: Of 2711 patients, 618 (22.8%) were iron deficient (= transferrin saturation [TSAT] < 16%) preoperatively, 173 (6.4% of the cohort) had an absolute iron deficiency (AID; TSAT < 16% and ferritin < 30 µg/L) and 445 (16.4%) had functional/mixed ID (TSAT < 16% and ferritin ≥ 30 µg/L). Corrected for Hb level, iron-deficient patients received significantly more red cell units than patients without ID (p = 0.026). AID was not associated with a significantly higher incidence of transfusions (7.5% of patients transfused; p = 0.12 after correction for Hb) than patients without ID, whereas patients with functional/mixed deficiency did receive significantly more transfusions (6.1%; p = 0.021) as compared to patients without ID (1.7%). CONCLUSION: Preoperative ID, in particular the functional/mixed type, was associated with a higher risk of receiving perioperative red cell transfusions as compared to patients without ID. Adequately treating ID might, therefore, reduce the need for perioperative red cell transfusions.

Platelets in ITP: Victims in Charge of Their Own Fate?

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The pathophysiological mechanisms leading to low platelet levels in ITP have not been resolved, but at least involve autoantibody-dependent and/or cytotoxic T cell mediated platelet clearance and impaired megakaryopoiesis. In addition, T cell imbalances involving T regulatory cells (Tregs) also appear to play an important role. Intriguingly, over the past years it has become evident that platelets not only mediate hemostasis, but are able to modulate inflammatory and immunological processes upon activation. Platelets, therefore, might play an immuno-modulatory role in the pathogenesis and pathophysiology of ITP. In this respect, we propose several possible pathways in which platelets themselves may participate in the immune response in ITP. First, we will elaborate on how platelets might directly promote inflammation or stimulate immune responses in ITP. Second, we will discuss two ways in which platelet microparticles (PMPs) might contribute to the disrupted immune balance and impaired thrombopoiesis by megakaryocytes in ITP. Importantly, from these insights, new starting points for further research and for the design of potential future therapies for ITP can be envisioned.

Guideline development for prevention of transfusion-associated graft-versus-host disease: reduction of indications for irradiated blood components after prestorage leukodepletion of blood components.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, commonly fatal complication of transfusion preventable by irradiation of blood units. The revision of the Dutch transfusion guideline addressed the question whether irradiation is still necessary if blood components are prestorage leukodepleted. We searched for published cases of TA-GVHD following transfusion of prestorage leukodepleted blood and through contacting haemovigilance systems. Six presumed cases were found, dating from 1998 to 2013. Four out of six patients had received one or more non-irradiated units despite recognised indications for irradiated blood components. In the countries providing information, over 50 million prestorage leukodepleted, non-irradiated, non-pathogen-reduced cellular components were transfused in a 10-year period. Potential benefits of lifting indications for irradiation were considered. These include reduced irradiation costs (€ 1.5 million annually in the Netherlands) and less donor exposure for neonates. Findings were presented in an invitational expert meeting. Recommendations linked to human leukocyte antigen similarity between donor and recipient or intra-uterine transfusion were left unchanged. Indications linked to long-lasting deep T-cell suppression were defined with durations of 6 or 12 months after end of treatment (e.g. autologous or allogeneic stem cell transplantation). Need for continued alertness to TA-GVHD and haemovigilance reporting of erroneous non-irradiated transfusions was emphasised.

Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia: a non-inferiority, multicentre, randomised trial.

BACKGROUND: Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin. METHODS: We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 109 cells per L before major surgery or less than 50 × 109 cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 109 cells per L before major surgery or 45 × 109 cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of -10%. This trial is registered with ClinicalTrials.gov, NCT01621204. FINDINGS: Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49-55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; pnon-inferiority=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI -2·1%; pnon-inferiority=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred. INTERPRETATION: Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles. FUNDING: GlaxoSmithKline and Novartis.

Remote Patient Monitoring in Adults Receiving Transfusion or Infusion for Hematological Disorders Using the VitalPatch and accelerateIQ Monitoring System: Quantitative Feasibility Study.

BACKGROUND: Frequent vital sign monitoring during and after transfusion of blood products and certain chemotherapies or immunotherapies is critical for detecting infusion reactions and treatment management in patients. Currently, patients return home with instructions to contact the clinic if they feel unwell. Continuous monitoring of vital signs for hematological patients treated with immunotherapy or chemotherapy or receiving blood transfusions using wearable electronic biosensors during and post treatment may improve the safety of these treatments and make remote data collection in an outpatient care setting possible. OBJECTIVE: This study aimed to evaluate patient experiences with the VitalPatch wearable sensor (VitalConnect) and to evaluate the usability of data generated by the physIQ accelerateIQ monitoring system for the investigator and nurse. METHODS: A total of 12 patients with hematological disorders receiving red blood cell transfusions, an intravenous (IV) proteasome inhibitor, or an IV immunotherapy agent were included in the study and wore the VitalPatch for 12 days. Patients completed questionnaires focusing on wearability and nurses completed questionnaires focusing on the usability of the VitalPatch. RESULTS: A total of 12 patients were enrolled over 9 months, with 4 receiving red blood cell transfusions, 4 receiving IV proteasome inhibitors, and 4 receiving IV immunotherapy. These patients were treated for diseases such as multiple myeloma, myelodysplastic syndrome, and non-Hodgkin lymphoma. Of these patients, 83% (10/12) were aged 60 years and older. A total of 4 patients (4/12, 33%) withdrew from the study (3 because of skin irritation and 1 because of patch connection issues). Patients wore biosensor patches at baseline and for 1-week post administration. Patient-reported outcomes (PROs) were collected at baseline, day 1, day 5, and day 8. No difference in the PRO was observed when nurses or patients applied the patch. PRO data indicated minimal impact on the patient's life. Ease of use, influence on sleep, impact on follow-up of health, or discomfort with continuous monitoring did not change between baseline and day 8. Changes in PRO were observed on day 5, where a 20% (2/10) increase in skin irritation was reported. Withdrawals because of skin irritation were reported in all cases when wearing the second patch. Nurses reported the placement of the VitalPatch to be easy and felt measurements to be reliable. CONCLUSIONS: Generally, the VitalPatch was well tolerated and shown to be an attractive device because of its wearability and low impact on daily activities in patients, therefore making it suitable for implementation in future studies.

Treatment strategies for polycythemia vera: Observations in a Dutch "real-world" cohort study.

OBJECTIVES: Assessment of "real-world" treatment strategies and outcome in Dutch polycythemia vera (PV) patients. METHODS: Retrospective chart review in 150 patients with PV (WHO 2008 diagnostic criteria) from 10 major non-academic hospitals in the Netherlands. RESULTS: Patients (median age 64 years, 49% male) frequently had cardiovascular risk factors (56%) and prior vascular events (31%). About 70% of patients were high-risk, based on ELN criteria. However, the majority of patients were treated with phlebotomies alone (55%). Cytoreduction with hydroxyurea (HU) was received by 44% as part of their initial therapy, with or without phlebotomies. The time to achieve the 45% hematocrit target was shortest in patients treated with phlebotomies with or without HU (125 ± 99 and 197 ± 249 days, respectively) compared to patients treated with only HU (232 ± 216 days). Leukocyte and platelet levels were lower in HU-treated patients, and ELN response targets were more often reached. During the median follow-up period of 4.1 years, 14 patients (9%) suffered a thrombotic vascular event. CONCLUSIONS: In Dutch clinical practice, there is major clinical variation in treatment strategies for PV. Phlebotomizing patients shorten the time to achieve hematocrit control, while HU better controls platelet and leukocyte levels. The thrombotic vascular event rate remains clinically significant.

Peri-Operative Eltrombopag or Immune Globulin for Patients with Immune Thrombocytopaenia (The Bridging ITP Trial): Methods and Rationale.

BACKGROUND: The Bridging ITP Trial is an open-label randomized trial designed to compare the oral thrombopoietin receptor agonist eltrombopag and intravenous immune globulin (IVIG) for patients with immune thrombocytopaenia (ITP) who require an increase in platelet count before elective surgery. Here, we report the study methods and rationale. METHODS: We designed a multi-centre, non-inferiority randomized trial comparing daily oral eltrombopag starting 3 weeks pre-operatively, and IVIG administered 1 week pre-operatively for patients with ITP requiring a platelet count increase prior to surgery. Starting dose of eltrombopag is 50 mg daily with a weekly pre-operative dose titration schedule, and treatment is continued for 1 week after surgical haemostasis is achieved. IVIG is administered at a dose of 1 to 2 g/kg 1 week pre-operatively with the allowance for a second dose within 1 week after surgical haemostasis. The objective of the study is to demonstrate non-inferiority of eltrombopag for the primary endpoint of achieving the pre-operative platelet count threshold (50 × 109/L for minor surgery; or 100 × 109/L for major surgery) and sustaining platelet count levels above the threshold for 1 week after surgical haemostasis is achieved, without the use of rescue treatment. Secondary endpoints include thrombosis, bleeding and patient satisfaction. CONCLUSION: The Bridging ITP Trial will evaluate the efficacy and safety of eltrombopag as an alternative to IVIG in the peri-operative setting for patients with ITP. The protocol was designed to provide a management strategy that can be applied in clinical practice. CLINICALTRIALS. GOV IDENTIFIER: NCT01621204.

Assessment of Self-Administration of Romiplostim in Patients with Immune Thrombocytopenic Purpura after Receipt of Home Administration Training Materials: a Cross-Sectional Study.

INTRODUCTION: Romiplostim is a subcutaneously administered thrombopoietin-receptor agonist approved in the European Union for self-administration (or administration by a caregiver) in selected adult patients with chronic primary immune thrombocytopenia refractory to other treatments. To mitigate the risk of medication errors due to self-administration, the manufacturer has implemented additional risk minimisation measures (RMM) in the form of a Home Administration Training (HAT) pack to support the training of both healthcare professionals (HCPs) (guide and checklist for patient selection and training) and patients (a preparation mat, quick guide booklet, step-by-step guide, self-administration diary and DVD/video). OBJECTIVE: The primary objective was to estimate the proportion of patients/caregivers who administered romiplostim correctly after HAT pack training. METHODS: A multicentre observational study was conducted to evaluate the effectiveness of the HAT pack by recording data on a standardised collection form during direct observation of patients/caregivers in the act of administering romiplostim at the first standard-of-care visit 4 weeks after training with the HAT pack. RESULTS: Among the 40 patients/caregivers enrolled across 12 study centres in eight European countries, 35 [87.5%; 95% confidence interval (CI) 73.9-94.5] administered romiplostim correctly, and five (12.5%; 95% CI 5.5-26.1) did not. CONCLUSION: The correct administration of romiplostim by most patients/caregivers supports the effectiveness of the HAT pack as an additional risk minimisation tool in the population and setting of this study.

Feasibility and efficacy of addition of individualized-dose lenalidomide to chlorambucil and rituximab as first-line treatment in elderly and FCR-unfit patients with advanced chronic lymphocytic leukemia.

Lenalidomide has been proven to be effective but with a distinct and difficult to manage toxicity profile in the context of chronic lymphocytic leukemia, potentially hampering combination treatment with this drug. We conducted a phase 1-2 study to evaluate the efficacy and safety of six cycles of chlorambucil (7 mg/m2 daily), rituximab (375 mg/m2 cycle 1 and 500 mg/m2 cycles 2-6) and individually-dosed lenalidomide (escalated from 2.5 mg to 10 mg) (induction-I) in first-line treatment of patients with chronic lymphocytic leukemia unfit for treatment with fludarabine, cyclophosphamide and rituximab. This was followed by 6 months of 10 mg lenalidomide monotherapy (induction-II). Of 53 evaluable patients in phase 2 of the study, 47 (89%) completed induction-I and 36 (68%) completed induction-II. In an intention-to-treat analysis, the overall response rate was 83%. The median progression-free survival was 49 months, after a median follow-up time of 27 months. The 2- and 3-year progression-free survival rates were 58% and 54%, respectively. The corresponding rates for overall survival were 98% and 95%. No tumor lysis syndrome was observed, while tumor flair reaction occurred in five patients (9%, 1 grade 3). The most common hematologic toxicity was grade 3-4 neutropenia, which occurred in 73% of the patients. In conclusion, addition of lenalidomide to a chemotherapy backbone followed by a fixed duration of lenalidomide monotherapy resulted in high remission rates and progression-free survival rates, which seem comparable to those observed with novel drug combinations including novel CD20 monoclonal antibodies or kinase inhibitors. Although lenalidomide-specific toxicity remains a concern, an individualized dose-escalation schedule is feasible and results in an acceptable toxicity profile. EuraCT number: 2010-022294-34.

Patient blood management in colorectal cancer patients: a survey among Dutch gastroenterologists, surgeons, and anesthesiologists.

INTRODUCTION: There is an increasing awareness to integrate patient blood management (PBM) within routine surgical care. Limited information about the implementation of PBM in colorectal cancer surgery is available. This is curious, as preoperative anemia, associated with increased morbidity, is highly prevalent in colorectal cancer patients. Present study aimed to assess the current PBM strategies in the Netherlands. METHODS: An online electronic survey was developed and sent to surgeons of the Dutch Taskforce Coloproctology (177 in total). In addition, for each hospital in which surgery for colorectal cancer surgery is performed (75 in total), the survey was sent to one gastroenterologist and one anesthesiologist. Analyses were performed using descriptive statistics. RESULTS: A total of 192 physicians responded to the survey (response rate 58.7%). In 73 hospitals (97.3%) the survey was conducted by at least one physician. Regarding the management of a mild-moderate preoperative anemia, no clear policy was reported in half of the hospitals (49.3%). In 38.7% of the hospitals, iron status was indicated to be measured during screening for colorectal cancer. In addition, in only 13.3% of the hospitals, iron status was measured by the anesthesiologist during preoperative assessment. CONCLUSION: The Present study shows a distinct variability in PBM practices in colorectal cancer care. Strikingly, this variability was not only seen between, but also within Dutch hospitals, demonstrated by often variable responses from physicians from the same institution. As a result, the present study clearly demonstrates the lack of consensus on PBM, resulting in a suboptimal preoperative blood management strategy.

Impact of extramedullary disease in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: a study from the Chronic Malignancies Working Party of the EBMT.

We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first-line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received up-front single (n=3391) or tandem transplantation (n=353) between 2005 and 2014 with available data on extramedullary involvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n=682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involvement in 139 (3.7%). More patients with extramedullary organ involvement had multiple involved sites (≥2; P<0.001). In a comparison of patients with single sites with patients without the disease, up-front transplantation resulted in at least similar 3-year progression-free survival (paraskeletal: P=0.86, and extramedullary organ: P=0.88). In single paraskeletal involvement, this translated less clearly into worse 3-year overall survival (P=0.07) while single organ involvement was significantly worse (P=0.001). Multiple organ sites were associated with worse outcome (P<0.001 and P=0.01). First-line treatment with tandem compared with single transplantation resulted in similar survival in patients with extramedullary disease at diagnosis (P=0.13 for both).

Short-term effect of preoperative intravenous iron therapy in colorectal cancer patients with anemia: results of a cohort study.

BACKGROUND: In the treatment of preoperative anemia, which is associated with increased postoperative morbidity, iron supplementation can replace blood transfusion and erythropoiesis-stimulating agents. The aim of this study was to assess the efficacy of preoperative intravenous (IV) iron infusion in optimizing hemoglobin (Hb) levels in anemic colorectal cancer patients. STUDY DESIGN AND METHODS: A retrospective cohort study was performed on patients who underwent surgery for colorectal cancer between 2010 and 2016 in a single teaching hospital. The primary outcome measure, the change in Hb level, was assessed by comparing anemic patients receiving usual care (UC; i.e. no iron therapy and no blood transfusion) with anemic patients receiving IV iron therapy (no blood transfusion). RESULTS: A total of 758 patients with colorectal cancer were eligible, of whom 318 (41.9%) had anemia. The IV and the UC groups included 52 and 153 patients with mean Hb levels at diagnosis of 6.3 and 6.9 mmol/L, respectively. In the IV group, preoperative Hb level was significantly increased compared to the UC group (0.65 mmol/L vs. 0.10 mmol/L, p < 0.001). High increase in Hb level after iron infusion was associated with initial higher transferrin and lower ferritin levels (high vs. poor responders: median transferrin 2.9 g/L vs. 2.7 g/L, median ferritin 12 µg/L vs. 27 µg/L). CONCLUSION: Implementation of IV iron therapy in anemic colorectal cancer patients leads to a distinct increase of preoperative Hb level. IV iron therapy is most effective in patients presenting with more severe anemia, and with higher transferrin and lower ferritin levels, markers for an absolute iron deficiency (ID), compared to functional ID.

Successful treatment of a noninhibitory antibody-mediated acquired factor X deficiency in a patient with marginal-zone lymphoma.

Prolonged clotting times were observed in a patient with spontaneous hemorrhage. Analysis showed severe factor X deficiency due to clearance by a noninhibitory antibody. Lymphadenopathy identified on imaging led to diagnosis of marginal B-cell lymphoma. Treatment of lymphoma with rituximab and chlorambucil resulted in complete disappearance of the bleeding disorder.

A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1-risk myelodysplastic syndrome.

Interleukin-6 (IL-6) may play an important role in the pathophysiology of anemia of inflammation associated with myelodysplastic syndrome (MDS). This double-blind, placebo-controlled, phase 2 study assessed the efficacy and safety of siltuximab, a chimeric anti-IL-6 monoclonal antibody, in patients with low- and intermediate-1-risk MDS who require transfusions for MDS anemia. Patients were randomized in a 2:1 ratio to siltuximab 15 mg kg(-1) every 4 weeks + best supportive care (BSC) or placebo + BSC for 12 weeks. The primary endpoint was reduction in red blood cell (RBC) transfusions to treat MDS anemia, defined as ≥50% relative decrease and ≥2-unit absolute decrease in RBC transfusions. Fifty and 26 patients were randomized to the siltuximab and placebo groups, respectively. The study did not meet its prespecified hypothesis, with six (12%) patients in the siltuximab group and one (3.8%) in the placebo group having reductions in RBC transfusions (P = 0.271). At the time of the planned futility analysis, the prespecified cutoff criteria were not met, and the study was terminated early due to lack of efficacy. No unexpected safety findings were observed. In conclusion, compared to placebo, treatment with siltuximab did not reduce RBC transfusions in transfusion-dependent patients with low- and intermediate-1-risk MDS. Future studies might explore siltuximab in patients with less iron overload and with elevated IL-6 levels and/or using higher doses for MDS.

Helicobacter pylori infection is not correlated with subclinical thrombocytopenia: a cross-sectional study.

In a small percentage of patients with immune thrombocytopenia (ITP), H. pylori eradication has a positive effect on platelet counts. Whether H. pylori infection is associated with a lower thrombocyte count in persons without clinical ITP is unknown. We performed a cross-sectional study to compare thrombocyte count between H. pylori infected (n=108) and H. pylori non-infected patients (n=600) who underwent a diagnostic gastroscopy. The mean thrombocyte count in H. pylori negative patients was 257 × 10(9)/l, in H. pylori positive patients 252 × 10(9)/l (mean difference 5 × 10(9)/l, 95% CI: -23 to 14). Subgroup analysis did not show significant differences either. In the patient group without apparent comorbidity, there were no subjects with thrombocyte counts <120. In 36 H. pylori positive patients in whom data post-eradication was available, platelet counts pre- and post-eradication were similar. In conclusion, this study could not demonstrate a lower thrombocyte count in H. pylori infected patients or in subgroups of H. pylori infected patients compared to non-infected subjects.