BackgroundIntravenous (i.v.) iron can improve anaemia of chronic disease and response to erythropoiesis-stimulating agents (ESAs), but data on its use in practice and without ESAs are limited. This study evaluated effectiveness and tolerability of ferric carboxymaltose (FCM) in routine treatment of anaemic cancer patients.Patients and methodsOf 639 patients enrolled in 68 haematology/oncology practices in Germany, 619 received FCM at the oncologist's discretion, 420 had eligible baseline haemoglobin (Hb) measurements, and 364 at least one follow-up Hb measurement. Data of transfused patients were censored from analysis before transfusion.ResultsThe median total iron dose was 1000 mg per patient (interquartile range 600–1500 mg). The median Hb increase was comparable in patients receiving FCM alone (1.4 g/dl [0.2–2.3 g/dl; N = 233]) or FCM + ESA (1.6 g/dl [0.7–2.4 g/dl; N = 46]). Patients with baseline Hb up to 11.0 g/dl and serum ferritin up to 500 ng/ml benefited from FCM treatment (stable Hb ≥11.0 g/dl). Also patients with ferritin >500 ng/ml but low transferrin saturation benefited from FCM treatment. FCM was well tolerated, 2.3% of patients reported putative drug-related adverse events.ConclusionsThe substantial Hb increase and stabilisation at 11–12 g/dl in FCM-treated patients suggest a role for i.v. iron alone in anaemia correction in cancer patients.

NCT 00567554, www.clinicaltrials.gov.

Recent Infectious Diseases Society of America guidelines for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections recommend maintaining vancomycin trough concentrations of 15-20 mg/L for serious infections. We conducted a systematic review and meta-analysis of all studies assessing the impact of low (<15 mg/L) vs. high (≥ 15 mg/L) vancomycin trough level on the efficacy of MRSA infections treatment. Four prospective and 12 retrospective studies were included (2003 participants). No significant difference was demonstrated between low and high vancomycin trough level for the outcome of all-cause mortality (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.78-1.46, I(2) = 28%). In studies evaluating mainly MRSA pneumonia, there was significantly higher mortality with low vancomycin level (OR 1.78, 95% CI 1.11-2.84). No significant difference was demonstrated in treatment failure rates (OR 1.25, 95% CI 0.88-1.78, I(2) = 51%). However, excluding one outlier study from the analysis, treatment failure became significantly higher in patients with low vancomycin trough level (OR 1.46, 95% CI 1.12-1.91, I(2) = 16%). Microbiologic failure rates were significantly higher in patients with low vancomycin levels (OR 1.56, 95% CI 1.08-2.26, I(2) = 0%). Nephrotoxicity was significantly higher with vancomycin levels of ≥ 15 mg/L. However, no cases of irreversible renal damage were reported. Current data on the effectiveness of higher vancomycin trough levels in the treatment of MRSA infections are limited to few prospective and mainly retrospective studies. Our findings support the current recommendations for maintaining vancomycin trough levels of ≥ 15 mg/L in the treatment of severe MRSA infections, although no difference in all-cause mortality was observed.

The use of erythropoiesis-stimulating agents (ESA) in cancer patients is still under debate. However, little is known about rationales, strategies, objectives, and effectiveness of anaemia treatments in common practice. The Cancer Anaemia Registry prospectively surveyed about 2000 cancer patients with anaemia throughout Germany. The main objectives of anaemia treatment regardless of modality were to improve quality of life (QOL) and to correct haemoglobin (Hb) levels. The Hb threshold for any anaemia treatment (means ± SD: 9.4 ± 1.2 g/dL) but not for blood transfusions (8.7 ± 1.0 g/dL) depended on cancer type and treatment strategy. Physicians preferred ESA as first-line treatment to prevent transfusions in patients with solid tumours, if they thought that chemotherapy caused the anaemia. If they suspected other causes or patients had lymphoproliferative malignancies, physicians preferred transfusions or attempted to correct underlying disorders; both mainly to improve QOL or prognosis. Effectiveness of all strategies was comparable. However, ESA most effectively prevented transfusions; primary transfusions appeared less suitable for correcting Hb or improving QOL. Using supportive treatments for QOL improvement was common whereas diagnostic measures and intravenous iron therapy were underused. Prospective clinical trials using QOL as end point and evaluating diagnostics in cancer-associated anaemia are warranted.

Objective. Treatment with erythropoiesis-stimulating factors (ESFs) can ameliorate anemia associated with cancer and chemotherapy. However, half of anemic cancer patients do not respond even to high doses. To determine factors that are predictive of a treatment response, a multicenter, prospective study was performed.Patients and Methods. Investigated factors were baseline erythropoietin, reticulocytes and soluble transferrin receptor (sTfR) after 2 weeks, and reticulocytes and hemoglobin after 4 weeks. Anemic patients with solid tumors received 150 g/week of darbepoetin concomitantly with chemotherapy. The dose was doubled if hemoglobin did not increase by >1 g/dl after 4 weeks. Patients were considered responders if hemoglobin increased by >2 g/dl or reached a level >12 g/dl within 8 -12 weeks.Results. In total, 196 patients were enrolled; 61% of the intention-to-treat (ITT) and 68% of the per-protocol population were responders. In the ITT population, the hemoglobin increase after 4 weeks indicated an 11-fold higher chance of response (odds ratio, 11.0; 95% confidence interval [CI], 5.1-23.6; sensitivity, 88%; specificity, 60%). In a multiple logistic regression model including all factors, the area under the receiver operating characteristic curve was 0.78 (95% CI, 0.71-0.84). The combination of sTfR after 2 weeks and hemoglobin after 4 weeks was as predictive as the combination of all five tested factors. Conclusion. So far, an early hemoglobin increase remains the single most predictive factor for response to ESF treatment. In contrast to anemic patients with lymphoproliferative malignancies, serum erythropoietin had little predictive value in patients with solid tumors. The Oncologist 2007;12: 748 -755 Disclosure of potential conflicts of interest is found at the end of this article.

The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the new comprehensive cytogenetic scoring system for MDS, chromosome 7 anomalies are no longer generally assigned to poor risk features but are thoroughly separated. However, der(1;7)(q10;p10), hereinafter der(1;7), is merged into the group labeled “any other single” and belongs to the intermediate risk group, just by definition due to lack of adequate clinical data. The aim of our international collaborative was to clarify the “real” prognostic impact of der(1;7) on a homogenous and well‐documented data base. We performed detailed analysis of 63 MDS patients with isolated der(1;7) constituting the largest cohort hitherto reported. Furthermore, clinical data are compared with those of patients with isolated del(7q) and isolated monosomy 7. Median overall survival (OS) of patients with der(1;7) is 26 months (hazard ratio (HR) 0.91 for del(7q) vs der(1;7) and 2.53 for monosomy 7 vs der(1;7)). The der(1;7) is associated with profound thrombocytopenia most probably causing the reduced OS which is in striking contrast to the low risk for AML transformation (HR 3.89 for del(7q) vs der(1;7) and 5.88 for monosomy 7 vs der(1;7)). Molecular karyotyping indicates that der(1;7) is generated in a single step during mitosis and that a chromosomal imbalance rather than a single disrupted gene accounts for malignancy. Thus, the current cytogenetic scoring system assigning isolated der(1;7) to the intermediate risk group is now confirmed by a sufficient data set.

Introduction: Multiple myeloma remains an incurable plasma cell malignancy which, despite improvements in overall survival over the last decade, is characterized by recurrent relapse and is associated with a poor prognosis. This study investigates the use of novel agents in current real-world clinical practice in the management of relapsed and/or refractory multiple myeloma (RRMM) in Germany over different lines of therapy. Methods: A retrospective chart review was conducted for patients with RRMM treated at multiple centers across Germany between May 2017 and June 2018. Variables included patient

Results of immunophenotypic examinations of peripheral blood and/or bone marrow (BM), involved in low-grade B-cell non-Hodgkin's lymphomas, were compared with the results of cytomorphological and histopathological examinations in 133 adult patients. 69 cases of chronic B-lymphocytic leukaemia (B-CLL), 16 centrocytic (CC) lymphomas, 14 centroblastic-centrocytic (CB/CC) lymphomas, 15 immunocytomas (IC), 10 cases of hairy cell leukaemia (HCL), four prolymphocytic leukaemias (PLL), two B-CLL in transformation, one splenic lymphoma with villous lymphocytes (SLVL), one hairy cell leukaemia variant (HCL-V), and one lymphocytic lymphoma (LC) were classified according to the Kiel and/or FAB classification. Leukaemic disease was found in 105 cases. The following markers were used for immunocytology (APAAP technique) of blood and/or BM smears: CD19, CD5, CD10, CD11c, CD14, CD21, CD22, CD23, CD25, CD38 and TdT. All cases tested showed CD19, but no TdT expression. Every case of HCL had a distinct phenotype with expression of CD11c, CD22 and CD25 and the lack of CD5 and CD23 antigens. In all other NHL cases a very heterogenous expression of CD-antigens with no significant correlations to the cytomorphological subtypes was found. The expression of CD5 is a frequent but inconstant finding in lymphoproliferative diseases other than B-CLL, so 50% of CB/CC, 75% of CC and 80% of IC were CD5 positive. Our results indicate that, with the exception of HCL, the diagnostic relevance of immunophenotyping for the classification of cytomorphologically and histopathologically defined subtypes in blood and/or BM is of very limited value.