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Background Catheter-related bloodstream infections (CRBSIs) are currently detected in patients with clinically suspicion. The aim of our study was to evaluate whether CRBSIs could be anticipated and detected in a subclinical stage by peptide nucleic acid fluorescence in situ hybridization (PNA FISH) using universal hybridization probes or acridine orange leucocyte cytospin (AOLC) tests in haematooncological patients with central venous catheters (CVCs) in situ. Materials and methods Peptide nucleic acid fluorescence in situ hybridization and AOLC tests using blood samples from one CVC lumen/port chamber in haematooncological patients were continuously performed. These results were compared to those obtained from routinely performed CRBSI diagnostic tests. Results One hundred and eighty-two patients with 342 catheter periods were investigated. Seventeen CRBSI cases were detected in 6466 CVC days by routine measures resulting in a CRBSI rate of 2·6/1000 catheter days. Two of 17 showed positive PNA FISH tests, and five positive AOLC test results before the diagnosis were established with routine measures. The screening revealed further seven patients with positive universal PNA FISH tests and 10 positive AOLC tests without symptoms indicative for infection and were therefore considered not to have CRBSI. Conclusions Sampling of only one CVC lumen/port chamber screening for CRBSI in haematooncological patients seems not to be a useful tool for anticipative diagnosis of CRBSI. Reasons for false-negative results might include origin of CRBSIs from the other CVC lumina not sampled for screening, and false-positive results might origin from catheter colonization without subsequent spread of micro-organisms into the peripheral bloodstream.

Low posaconazole plasma concentrations (PPCs) are associated with breakthrough invasive mould infections among patients with haematological malignancies. This study evaluated the influence of structured personal on-site patient education on low PPCs. The study was conducted from July 2012 to May 2013 at the Division of Hematology, Medical University Hospital of Graz (Graz, Austria). PPCs were measured in all patients with haematological malignancies receiving the drug prophylactically. Concentrations above the target of 0.5 mg/L were defined as satisfactory and those below this concentration as low. In patients with low PPCs, structured personal on-site education regarding the intake of posaconazole (e.g. intake with fatty/acid food, prevention of nausea and vomiting) was performed. In total, 258 steady-state PPCs were measured in 65 patients [median PPC 0.59 mg/L, interquartile range 0.25-0.92 mg/L; 141/258 (54.7%) satisfactory]. Diarrhoea was the strongest predictor of low PPCs in the multivariate analysis. Initial steady-state PPCs were sufficient in 29 patients and low in 36 patients. Of the 36 patients with low initial steady-state PPCs, 8 were either discharged or antifungal therapy was modified before a follow-up PPC was obtained; in the remaining 28 patients, personal on-site education was performed. In 12/28 patients (43%) the personal on-site education led to sufficient levels, whilst in 16 (57%) PPCs stayed below the target, although increasing from0.2 mg/L to0.3 mg/L in 6 of these patients. In conclusion, personal education appears to be a promising tool to increase low PPCs.

Data on efficacy and safety of azacitidine in acute myeloid leukemia (AML) with >30 % bone marrow (BM) blasts are limited, and the drug can only be used off-label in these patients. We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry (clinicaltrials.gov identifier NCT01595295). We herein update this report with a population almost twice as large (n = 302). This cohort included 172 patients with >30 % BM blasts; 93 % would have been excluded from the pivotal AZA-001 trial (which led to European Medicines Agency (EMA) approval of azacitidine for high-risk myelodysplastic syndromes (MDS) and AML with 20–30 % BM blasts). Despite this much more unfavorable profile, results are encouraging: overall response rate was 48 % in the total cohort and 72 % in patients evaluable according to MDS-IWG-2006 response criteria, respectively. Median OS was 9.6 (95 % CI 8.53–10.7) months. A clinically relevant OS benefit was observed with any form of disease stabilization (marrow stable disease (8.1 months), hematologic improvement (HI) (9.7 months), or the combination thereof (18.9 months)), as compared to patients without response and/or without disease stabilization (3.2 months). Age, white blood cell count, and BM blast count at start of therapy did not influence OS. The baseline factors LDH >225 U/l, ECOG ≥2, comorbidities ≥3, monosomal karyotype, and prior disease-modifying drugs, as well as the response-related factors hematologic improvement and further deepening of response after first response, were significant independent predictors of OS in multivariate analysis. Azacitidine seems effective in WHO-AML, including patients with >30 % BM blasts (currently off-label use). Although currently not regarded as standard form of response assessment in AML, disease stabilization and/or HI should be considered sufficient response to continue treatment with azacitidine. Electronic supplementary material The online version of this article (doi:10.1007/s00277-014-2126-9) contains supplementary material, which is available to authorized users.

Dear Editor, In 1993, a 49-year-old male patient presented with pain in the left shoulder. CT and magnetic resonance tomography (MRT) scans revealed a lesion in the third thoracic vertebra with preand paravertebral soft tissue involvement. Laminectomy of the second and third thoracic vertebra and stabilizing spondylodesis were performed, and the tumor was partially removed. By immunohistochemical examination, the lesion was classified as plasmacytoma, IgA kappa. Serum electrophoresis showed no M protein. By immunofixation, an IgA kappa paraprotein was identified and immunoglobulin A was slightly elevated. All other laboratory parameters including peripheral blood counts, renal function, calcium, and other polyclonal immunoglobulins were within the normal range. The bone marrow puncture result and skeletal survey were without pathologic findings leading to the diagnosis of a localized plasmacytoma (solitary plasmacytoma of the bone). Therapeutic radiation therapy (36 Gy) involving the upper thor ac i c ve r t eb r ae induced comple t e r emi s s i on . Paraproteinemia resolved within 8 months. In 2006, back pain occurred without neurologic deficits. CT results showed an osteolytic lesion in the third thoracic vertebral body with subtotal obliteration of the spinal canal. Dorsal stabilization operation was performed. Histological workup again showed IgA kappa plasmacytoma. Serum heavy and light chains were in the normal range, and immunofixation again showed an IgA kappa paraprotein. Bonemarrow results were inconspicuous, and further imaging showed no other lesions. Due to the high risk of neurotoxicity by a second irradiation therapy at the same location, we treated the patient with four cycles of bortezomib, doxorubicin, and dexamethasone (PAD regimen) resulting only in partial tumor remission. PET scan still showed pathologic F-18 fluorodeoxyglucose (FDG) uptake consistent with persistent disease (see Fig. 1a). The patient was offered stem cell apheresis and autologous stem cell transplantation which he denied. Alternatively, he was referred to the CyberKnife Center Munich Groshadern. Radiosurgery using the CyberKnife technique was chosen for further therapy. In July 2007, the patient was treated with a single irradiation dose of 18 Gy prescribed to the 70 % isodose using 154 small intersecting radiation beams. Since July 2008, MRT and PET-CT have repeatedly shown complete disappearance of contrast agent and FDG enhancement, respectively, at the site of the former lesion (see Fig. 1b). Further investigations did not display any pathologic findings by laboratory examinations (December 2013) as well as imaging including MRI and PET-CT (June 2014) to date. No significant neurotoxicity was observed after radiosurgery. To conclude, solitary plasmacytoma is highly radiosensitive implicating radiotherapy as a first-line treatment [1–3]. The main problem after successful initial treatment is progression to multiple myeloma, while strictly local relapse is rare [1–3]. Due to the lack of guidelines, treatment in local relapse is experimental. Radiosurgery in plasmacytoma treatment has * Georg Theiler georg.theiler@gmx.at

There are only a few studies dealing with the detection and clinical impact of calcium pyrophosphate (CPPD) crystals in patients with rheumatoid arthritis (RA) published to date. In particular, data determined by the cytospin technique, which is an effective tool to enhance the crystal detection rate, are lacking. The objectives of this study were to determine the prevalence of CPPD crystals in the synovial fluid (SF) of patients with RA and to investigate whether the detection of CPPD crystals is correlated with demographic, clinical and serological features. We examined 113 consecutive SF samples of patients with RA, obtained from therapeutic arthrocentesis of knee joints. After cytocentrifugation, the sediments were examined by polarized microscopy for the occurrence of CPPD crystals. Demographic, clinical and serological data, acquired from the medical records, were compared between crystal-positive and crystal-negative subjects. CPPD crystals were observed in 20 of the 113 cases, representing 17.7 %. CPPD-positive and CPPD-negative subjects did not differ significantly in sex, duration of disease, Steinbrocker radiologic stage, disease activity score 28, as well as serum rheumatoid factor and anti-CCP positivity. Patients positively tested for CPPD crystals had a significantly higher age than CPPD-negative patients (p

Puumala virus infection causes epidemic nephropathia (NE), a certain type of haemorrhagic fever with renal syndrome (HFRS). Myopic shift is considered a pathognomonic sign of NE and HFRS but rates of ocular involvement vary. The aim of the study was to evaluate whether clinical and laboratory findings are associated with ophthalmic involvement in NE in Austria. We found that blurred vision and myopic shift are frequent in Puumala virus infections in Austria but are independent of disease severity.

Background The prognosis of patients with relapsed/refractory acute myeloid leukemia (AML) following intensive chemotherapy (IC) is poor; furthermore, treatment options for these patients are limited. Few studies have assessed outcomes of azacitidine (AZA) in a relapsed/refractory setting.1–3 Response rates and survival in these studies have been variable. Methods The Austrian AZA Registry was initiated to gain a comprehensive view of the use, safety and efficacy of AZA in a broad range of ‘real-life’ AML patients. The sole inclusion criteria were the diagnosis of AML according to World Health Organization (WHO) criteria and treatment with ≥1 dose of AZA. Here, we assess clinical outcomes in patients with newly diagnosed AML (AZA 1st line) vs patients with relapsed/refractory AML following IC and/or low-dose chemotherapy/other disease-modifying therapy (AZA ≥2nd line). Results Baseline characteristics were generally comparable between patients treated with AZA 1st line (n=170) and AZA after IC (n=127), or AZA ≥2nd line (n=176), respectively (Figure 1). However, pre-treated patients had a significantly lower proportion of patients younger than 75 years (18.9 and 29.0 vs 59.4% for AZA after IC [p Median time from initial diagnosis to AZA treatment was shorter for patients treated with AZA 1st line than AZA after IC or ≥2nd line (0.5, 9.2 and 7.8 months, respectively). Median number of cycles was higher for patients who received AZA 1st line than AZA after IC or ≥2nd line (6 [range 1–46], 3 [range 1–27] and 3 [range 1–35], respectively). Time from AZA stop to death was 1.8 months for the AZA 1st line and ≥2nd line cohorts, and 2.1 months for patients receiving AZA after IC. There was no significant difference in overall response rate (ORR) according to International Working Group (IWG) 2003 criteria4 (complete response [CR] + CR with incomplete blood count recovery [CRi] + partial response [PR]) in patients treated with AZA 1st line compared with pre-treated patients (24.4 and 22.2 vs 35.9% for AZA after IC [p=0.139] and AZA ≥2nd line vs AZA 1st line [p=0.072], respectively; Figure 1). Furthermore, rates of hematologic improvement (HI) according to IWG 2006 criteria5 were also similar (53.2 and 51.0 vs 63.3% for AZA after IC [p=0.349] and AZA ≥2nd line vs AZA 1st line [p=0.250], respectively; p=0.463; Figure 1). When ORR and rate of HI were combined, the difference remained non-significant (Figure 1). Median overall survival (OS) was significantly higher with AZA 1st line than AZA after IC (12.8 vs 7.6 months, p=0.005) or ≥2nd line (12.8 vs 6.0 months, p0% (p=0.01), lactate dehydrogenase >225IU/L (p=0.012), and poor-risk cytogenetics (according Medical Research Council [MRC] criteria; p=0.011). Conclusion This study represents the largest cohort of relapsed/refractory AML patients treated with AZA, comprising almost four times as many patients (n=176) than the largest cohorts reported to date (n=47). Despite a shorter OS than patients treated with AZA 1st line, response rates in patients who received AZA as a ≥2nd line therapy were encouragingly high and similar to response rates of AZA 1st line patients. Median OS of 7.6 months in relapsed patients or those who are refractory to IC, which generally confers a dismal prognosis (median OS: ~3 months),6,7 is promising. Thus, salvage therapy with AZA is a treatment option for patients with relapsed/refractory AML, which should be further pursued in clinical trials. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pleyer: Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AOP Orphan Pharmaceuticals: Honoraria; Celgene: Consultancy, Honoraria. Off Label Use: Vidaza (azacitidine) is indicated for the treatment of adult AML patients who are not eligible for haematopoietic stem cell transplantation with 20–30 % blasts and multi-lineage dysplasia, according to WHO classification. This cohort also includes AML-patients with >30% bone marrow blasts.. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy. Stauder:Novartis: Research Funding; Ratiopharm: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharm: Consultancy, Honoraria. Pfeilstöcker:Novartis: Consultancy, Honoraria; Janssen-Cilag: Honoraria; Celgene: Consultancy, Honoraria. Lang:Celgene: Consultancy. Sperr:Phadia: Research Funding; Novartis: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Valent:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Greil:Sanofi Aventis: Honoraria; Roche: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; GSK: Research Funding; Ratiopharm: Research Funding.

Background Recent phase III data indicate that azacitidine (AZA) is active, and well tolerated, in patients with acute myeloid leukemia (AML) and baseline white blood cell (WBC) counts of Methods In this retrospective study of the Austrian AZA Registry (N=346), we assessed outcomes in patients with WHO-AML who received ≥1 dose of AZA, according to baseline WBC count. Patients were divided according to WBC Results A comparison of baseline characteristics between the two groups revealed significantly higher levels of serum lactate dehydrogenase (LDH), peripheral blood (PB) and bone marrow (BM) blasts in patients with WBC ≥15G/L vs those with WBC In the 1st line setting, overall response rate (ORR) was similar in the WBC In contrast, in the ≥2nd line setting, ORR was significantly higher in the WBC Different baseline factors appeared to significantly impact OS in the 0% and LDH >225IU/L negatively affected OS, irrespective of treatment line. Adverse cytogenetics reached statistical significance for the whole 3, primarily in the AZA 1st line setting. Conclusions Previous retrospective studies have suggested that WBC ≥15G/L has a negative impact on OS in AML patients treated with AZA.2,3 This report is the first to describe the impact of WBC ( 1. Dombret H, et al. Oral presentation at EHA 2014. Abstract LB-2433 2. Thepot S, et al. Am J Hematol 2014;89:410–6 3. van der Helm LH, et al. Leuk Res 2013;37:877–82 4. Cheson BD, et al. J Clin Oncol 2003;21:4642–9 5. Cheson BD, et al. Blood 2006;108:419–25 Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pleyer: Celgene: Consultancy, Honoraria; AOP Orphan Pharmaceuticals: Honoraria; Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Off Label Use: Vidaza (azacitidine) is indicated for the treatment of adult AML patients who are not eligible for haematopoietic stem cell transplantation with 20–30 % blasts and multi-lineage dysplasia, according to WHO classification. This cohort also includes AML-patients with >30% bone marrow blasts.. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy. Stauder:Ratiopharm: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Research Funding. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharm: Consultancy, Honoraria. Pfeilstöcker:Janssen-Cilag: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lang:Celgene: Consultancy. Sperr:Phadia: Research Funding; Novartis: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Valent:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Greil:Amgen: Honoraria, Research Funding; Eisai: Honoraria; Mundipharma: Honoraria, Research Funding; Merck: Honoraria; Janssen-Cilag: Honoraria; Genentech: Honoraria, Research Funding; Novartis: Honoraria; Astra-Zeneca: Honoraria; Boehringer-Ingelheim: Honoraria; Pfizer: Honoraria, Research Funding; Roche: Honoraria; Sanofi Aventis: Honoraria; GSK: Research Funding; Ratiopharm: Research Funding; Celgene: Consultancy, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria.

Background Approximately 10% of cases of acute myeloid leukemia (AML) arise following exposure to chemotherapy (treatment-related AML [tAML]). Compared to de novo AML patients, tAML patients have a poor prognosis, not least due to a higher proportion having adverse cytogenetics. Treatment options for tAML patients are limited and outcomes remain dismal. Median overall survival (OS) of 6.9 mo as of initial presentation, with 25% deaths within one month of diagnosis, was reported for a large cohort of tAML patients, with individualized treatments ranging from supportive care, to intensive chemotherapy (IC) and bone marrow (BM) transplantation.1 Few studies have assessed azacitidine (AZA) in patients with tAML, and those that have, did not report separate outcomes for this subgroup.2–4 Methods Here, we compare a subgroup of tAML patients (n=27) with patients with other World Health Organization (WHO)-AML subgroups (n=319) from the Austrian AZA Registry. The aim of the registry was to gain insight of the use, safety and efficacy of AZA in ‘real-world’ AML patients. The sole inclusion criteria were the diagnosis of WHO-AML and treatment with ≥1 dose of AZA. Results Baseline characteristics were compared between patients with tAML and WHO-AML: median age, gender, percentage with myelodysplatic syndrome (MDS)-related features, serum lactate dehydrogenase (LDH) level, and median peripheral blood and BM blasts were similar between both cohorts. However, tAML patients had poorer Eastern Cooperative Oncology Group Performance Status (ECOG PS) scores, more comorbidities, and a higher proportion of high-risk cytogenetics compared with WHO-AML patients. Of patients with tAML, 41% received AZA as 1st line therapy and 59% received AZA as ≥2nd line therapy. Baseline characteristics of these two subgroups were also comparable, except that tAML patients treated with AZA 1st line were older, had poorer ECOG PS and worse cytogenetics than ≥2nd line patients, which is in line with what would be expected from a cohort not deemed eligible for IC (Figure 1). Median number of AZA cycles was 4 (range 1–25) for tAML patients and 4 (range 1–46) for WHO-AML patients. Median time from AZA stop to death was 1.9 vs 1.8 mo for patients with tAML vs other WHO-AML subgroups. The overall response rate (ORR; International Working Group [IWG] 2003 criteria5) as well as the rate of hematologic improvement (HI; IWG 2006 criteria6) were similar for patients with tAML vs WHO-AML treated with AZA (complete response [CR] + CR with incomplete blood count recovery [CRi] + partial response [PR]: 22.2 vs 29.5%; and HI: 58.8 vs 57.7%, respectively; Figure 1). Median OS was similar for patients with tAML vs WHO-AML (8.9 vs 9.4 mo; p=0.147; Figure 1), but was longer for responders than non-responders in both groups of patients. Relapse-free survival was 7.7 vs 9.1 mo for patients with tAML vs WHO-AML. In univariate analyses, baseline factors that significantly affected OS for tAML patients were LDH >225IU/L (p Patients with tAML who received AZA 1st line achieved a significantly higher ORR than those who received AZA ≥2nd line (36.4 vs 12.5%; p Conclusions This represents the largest study reporting outcomes of tAML patients treated with AZA. Survival of tAML patients with AZA was comparable to that achieved in other WHO-AML subgroups, suggesting that AZA is a feasible treatment option for this poor prognostic subgroup. The OS data compare favorably to OS data reported for IC1 and are encouraging. Based on these ‘real-world’ data, randomized trials should assess AZA in tAML patients. 1. Smith SM, et al. Blood 2003;102:43–52 2. Bally C, et al. Leuk Res 2013;37:637–40 3. Fianchi L, et al. J Hematol Oncol 2012;5:44 4. Pleyer L, et al. Ann Hematol 2014; epub ahead of print 5. Cheson BD, et al. J Clin Oncol 2003;21:4642–9 6. Cheson BD, et al. Blood 2006;108:419–25 Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pleyer: Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AOP Orphan Pharmaceuticals: Honoraria; Celgene: Consultancy, Honoraria. Off Label Use: Vidaza (azacitidine) is indicated for the treatment of adult AML patients who are not eligible for haematopoietic stem cell transplantation with 20–30 % blasts and multi-lineage dysplasia, according to WHO classification. This cohort also includes AML-patients with >30% bone marrow blasts.. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy. Stauder:Celgene: Consultancy, Honoraria, Research Funding; Ratiopharm: Honoraria, Research Funding; Novartis: Research Funding. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharm: Consultancy, Honoraria. Pfeilstöcker:Janssen-Cilag: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lang:Celgene: Consultancy. Sperr:Phadia: Research Funding; Novartis: Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Valent:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Greil:Sanofi Aventis: Honoraria; Roche: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; GSK: Research Funding; Ratiopharm: Research Funding.

Background Few data exist reporting the incidence of World Health Organization (WHO)-defined acute myeloid leukemia (AML) subgroups in adults in Europe,1 but the incidence of AML with myelodysplastic-related features (MRF) may be higher than initially reported.2–4 Whether the presence of multilineage dysplasia has an independent prognostic impact in AML is still controversial.5,6 However, AML patients with preceding myelodysplastic syndrome (MDS)/myeloproliferative neoplasm and/or MDS-related cytogenetics (Medical Research Council [MRC]) have been shown to have poorer survival than AML-not otherwise specified (NOS).7 Previous studies of AML patients treated with azacitidine (AZA) included AML-MRF patients, but did not report on outcomes separately.3,4, 8–12 Methods Due to the lack of data assessing the prognostic impact of AML-MRF in elderly AML patients treated with AZA, we analyzed patients with AML-MRF from the Austrian AZA Registry, which was initiated to gain a comprehensive view of the safety and efficacy of AZA in ‘real-life’ patients. Similar to the approach taken by others who assessed the effect of AML-MRF irrespective of treatment modality,7 patients with AML and recurrent cytogenetic abnormalities (RCA), and treatment-related AML (tAML) based on the WHO 2008 classification13 were excluded, as these subsets have particularly good (AML-RCA) or dismal prognosis (tAML), respectively. Results The AML-MRF group comprised 217 patients (AZA 1st line, n=121; AZA ≥2nd line, n=96) and the AML-NOS group comprised 90 patients (AZA 1st line, n=33; AZA ≥2nd line, n=57). Baseline characteristics were comparable except AML-MRF patients had worse Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) scores and a higher proportion of high-risk cytogenetics (Figure 1). The latter is expected as most high-risk cytogenetic abnormalities are defined as MDS-related.13 Median time from diagnosis to AZA start was 6 months for AZA ≥2nd line. The median number of AZA cycles was 4 (range 1–35) for AML-MRF patients and 4.5 (range 1–46) for AML-NOS patients. The overall response rate (ORR)14 was similar for AML-MRF vs AML-NOS patients (complete response [CR] + CR with incomplete blood count recovery [CRi] + partial response [PR]: 29.0 vs 33.3%, respectively; p=0.586). Rates of hematologic improvement15 were similar for AML-MRF vs AML-NOS patients (57.9 vs 57.4%; p=0.964). Median duration of response was 7.0 vs 5.5 mo, respectively. ORR was similar for AML-MRF and AML-NOS patients irrespective of AZA treatment line (Figure 1). Median overall survival (OS) for AML-MRF vs AML-NOS patients was 9.4 vs 9.7 mo for the total cohort (p=0.490; Figure 2), and 13.1 vs 10.8 mo for patients treated with AZA 1st line. For responding patients, median OS, response duration and relapse-free survival were numerically longer for AML-MRF than AML-NOS patients within the total cohort (17.1 vs 12.6; 7.0 vs 5.5; and 9.8 vs 8.5 mo), and even more so in the AZA 1st line cohort (19.7 vs 12.6; 7.4 vs 3.9; and 10.5 vs 7.9 mo). In univariate analyses, baseline factors that significantly negatively impacted OS in AML-MRF patients treated with AZA were peripheral blood blasts >0% (p=0.025), Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2 (p=0.004), >3 comorbidities (p=0.004), and poor cytogenetics (p=0.001). Notably, none of these factors showed statistical significance for AML-NOS patients. Conclusions This represents the first and largest report comparing outcomes of AML-MRF vs AML-NOS patients treated with AZA. Outcomes of AML-MRF patients were similar to patients with other AML-NOS subgroups. AZA seems a feasible treatment option for these patients despite the reported poor prognostic impact of MRF. 1. Sant M, et al. Blood 2010;116:3724–34 2. Quintas-Cardama A, et al. Blood 2012;120:4840–5 3. Pleyer L, et al. Ann Hematol 2014 [Epub ahead of print] 4. Thepot S, et al. Am J Hematol 2014;89:410–6 5. Wandt H, et al. Blood 2008;111:1855–61 6. Gahn B, et al. Leukemia 1996;10:946–51 7. Miesner M, et al. Blood 2010;116:2742–51 8. van der Helm L, et al. Leuk Res 2013;37:877–82 9. Gavillet M, et al. Haematologica 2012;97:1929–31 10. Maurillo L, et al. Cancer 2012;118:1014–22 11. Ivanoff S, et al. Am J Hematol 2013;88:601–5 12. Al-Ali HK, et al. Leuk Lymphoma 2011;53:110–7 13. Swerdlow SH, et al. IARC press 2008 14. Cheson BD, et al. J Clin Oncol 2003;21:4642–9 15. Cheson BD, et al. Blood 2006;108:419–25 Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pleyer: Bristol-Myers Squibb: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; AOP Orphan Pharmaceuticals: Honoraria; Celgene: Consultancy, Honoraria. Off Label Use: Vidaza (azacitidine) is indicated for the treatment of adult AML patients who are not eligible for haematopoietic stem cell transplantation with 20–30 % blasts and multi-lineage dysplasia, according to WHO classification. This cohort also includes AML-patients with >30% bone marrow blasts. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy. Stauder:Novartis: Research Funding; Ratiopharm: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharm: Consultancy, Honoraria. Pfeilstöcker:Janssen-Cilag: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lang:Celgene: Consultancy. Sperr:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Phadia: Research Funding. Valent:Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Greil:Sanofi Aventis: Honoraria; Roche: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; GSK: Research Funding; Ratiopharm: Research Funding.

Background Several studies, including retrospective analyses of patient registries1,2 and a subanalysis of the phase III MDS-AZA-001 trial3 suggest that poor-risk cytogenetics negatively impact overall survival (OS) in patients with myelodysplastic syndrome (MDS) and World Health Organization (WHO)-defined acute myeloid leukemia (AML) treated with azacitidine (AZA). There are few data available to indicate whether AZA has improved clinical activity vs conventional care in AML patients with adverse cytogenetics. However, in a subanalysis of MDS-AZA-001 (MDS and AML [20–30% bone marrow blasts]) patients with –7/–7q abnormalities had better OS with AZA than low-dose cytarabine (21.4 vs 3.5 months, respectively) supporting significant activity of AZA in patients with adverse cytogenetics.4 Methods In this retrospective study of the Austrian AZA Registry (N=346), we compared patients with WHO-AML and intermediate- (n=228) vs high-risk (n=74) cytogenetics according to Medical Research Council (MRC) criteria. Outcomes were also assessed with respect to AZA treatment line. Results The intermediate-risk cytogenetics group comprised 228 patients (AZA 1st line, n=109; AZA ≥2nd line, n=119), and the high-risk cytogenetics group comprised 74 patients (AZA 1st line, n=39; AZA ≥2nd line, n=35; Figure 1). Comparison of baseline characteristics of both groups revealed significant differences with regard to prevalence of males and Eastern Cooperative Oncology Group Performance Status (ECOG PS) >2 for patients with high-risk cytogenetics receiving AZA 1st line, but not in those receiving AZA ≥2nd line. Peripheral blood blasts were present in a significantly larger proportion of high- than intermediate-risk patients (Figure 1). In patients who received AZA 1st line, median number of AZA cycles was 6 for both the intermediate- and high-risk cytogenetic groups (range: 1–46 and 1–25, respectively). Median time from diagnosis to AZA start was 7.6 months for AZA ≥2nd line. Median time from AZA stop to death was In the whole cohort, the overall response rate (ORR) according to International Working Group (IWG) 2003 criteria5 was similar for patients with intermediate- and high-risk cytogenetics (complete response [CR] + CR with incomplete blood count recovery [CRi] + partial response [PR]: 32.0 vs 20.3%; p=0.106; Figure 1). Rates of hematologic improvement (HI) according to IWG 2006 criteria6 were also not significantly different (54.4 vs 75.6; p=0.063), and when ORR and HI were combined, the difference remained non-significant (47.4 vs 46.0%; p=0.885; Figure 1). Median OS was consistently higher in patients with intermediate- than high-risk cytogenetics (9.8 vs 5.4 months for the total cohort; p=0.046 [Figures 1 and 2a]; 13.5 vs 9.5 months for AZA 1st line [not significant]; and 7.6 vs 3.5 months for AZA ≥2nd line; p=0.005 [Figure 1]). However, median OS for responding patients (CR/CRi/PR/HI) was similar for patients with intermediate- and high-risk cytogenetics, irrespective of treatment line (19.9 vs 19.3 months for all responders; 20.5 vs 21.7 months for AZA 1st line; and 18.5 vs 15.0 months for AZA ≥2nd line). Furthermore, presence of a monosomal karyotype had a significant negative impact on OS (Figure 2b). None of the baseline factors analyzed had an impact on OS in patient subgroups with intermediate- or high-risk cytogenetics, except number of comorbidities >3. Conclusions Here, we compared outcomes of 302 WHO-AML patients with intermediate- vs high-risk cytogenetics treated with AZA. In line with recent data of MDS patients,1 baseline cytogenetics did not seem to have a significant effect on response to AZA. However, in agreement with other studies of AZA in MDS/WHO-AML patients,1–3 high-risk cytogenetics had a negative impact on survival compared with intermediate-risk cytogenetics in WHO-AML treated with AZA. 1. Sebert M, et al. Oral presentation at ASH 2013. Abstract 389 2. Thepot S, et al. Am J Hematol 2014;89:410–6 3. Fenaux P, et al. J Clin Oncol 2010;28:562–9 4. Fenaux P, et al. Br J Haematol 2010;149:244–9 5. Cheson BD, et al. J Clin Oncol 2003;21:4642–9 6. Cheson BD, et al. Blood 2006;108:419–25 Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pleyer: AOP Orphan Pharmaceuticals: Honoraria; Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Off Label Use: Vidaza (azacitidine) is indicated for the treatment of adult AML patients who are not eligible for haematopoietic stem cell transplantation with 20–30 % blasts and multi-lineage dysplasia, according to WHO classification. This cohort also includes AML-patients with >30% bone marrow blasts.. Burgstaller:AOP Orphan Pharmaceuticals: Honoraria; Novartis: Honoraria; Mundipharma: Honoraria; Celgene: Consultancy. Stauder:Novartis: Research Funding; Ratiopharm: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharm: Consultancy, Honoraria. Pfeilstöcker:Janssen-Cilag: Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Lang:Celgene: Consultancy. Sperr:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Phadia: Research Funding. Valent:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Greil:Sanofi Aventis: Honoraria; Roche: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; GSK: Research Funding; Ratiopharm: Research Funding.

Previous studies suggest that hyperprolactinaemia might have adverse effects on lipid and glucose metabolism. We therefore aimed to evaluate whether dopamine agonist treatment with cabergoline has significant effects on blood lipids, fasting glucose and HbA1c levels in patients with micro- or macroprolactinoma. In this retrospective observational study the main outcome measures are changes in parameters of glucose and lipid metabolism compared at hyperprolactinaemia and after achievement of normoprolactinaemia by cabergoline treatment. We enrolled 53 study participants (22 females; median [interquartile range] age: 40.0 [27.5 to 50.0] years), 22 (41.5 %) with micro-, and 31 (58.5 %) with macroprolactinomas. After a median follow-up of 9 months, prolactin levels decreased from 220.6 (80.7–913.4) to 11.2 (3.5–18.7) ng/mL (p

Recent data suggest that azacitidine may be beneficial in CMML. We report on 48 CMML-patients treated with azacitidine. Overall response rates were high (70% according to IWG-criteria, including 22% complete responses). Monocyte count and cytogenetics adversely affected survival, whereas age, WHO-type, FAB-type, and spleen size did not. Matched-pair analyses revealed a trend for higher two-year-survival for azacitidine as compared to best supportive care (62% vs. 41%, p=0.067) and longer OS for azacitidine first-line vs. hydroxyurea first-line (p=0.072, median OS 27.7 vs. 6.2 months). This report reinforces existing evidence that azacitidine is safe and efficacious in both myelodysplastic and myeloproliferative CMML.