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Hyperdiploidy (HRD) and specific immunoglobulin heavy locus (IGH) translocations are primary chromosomal abnormalities (CA) in multiple myeloma (MM). In this retrospective study of 794 MM patients we aimed to investigate clinical features and common CA including gain(1q) in separate subgroups defined by primary CA. In the entire group, we confirmed that gain(1q) was associated with short time to next treatment and adverse overall survival (OS). The impact was worse for four or more copies of 1q21 as compared to three copies. However, in a subgroup of patients with clonal gain(11q) and without known primary IGH translocations (CG11q), already three copies of 1q21 were associated with a poor outcome; in the absence of gain(1q), patients in this subgroup had a remarkably long median OS of more than nine years. These cases were associated with HRD, coexpression of CD56 and CD117, male gender, and IgG subtype. In non‐CG11q patients, four or more copies of 1q21 (but not three copies) had a significant adverse impact on outcome. Several associations with CA and clinical findings were observed for the defined subgroups. As an example, we found a predominance of early tetraploidy, plasma cell leukemia, and female gender in the t(14;16) subgroup. Our results underscore the importance of subgrouping in MM.

Polycythemia vera (PV) is a clonal disease arising from hematopoietic stem cells. Erythrocytosis is the hallmark of the disease but leukocytosis, thrombocytosis and splenomegaly may also be present. Thromboembolic complications occur in about 20% of patients. Circulatory disturbances as well as pruritus represent frequent symptoms of the disease. Mutations in the JAK2 gene are present in 95% of patients in exon 14 (V617F) and in 3% in exon 12. The main goal of the treatment for patients with PV is the prevention of thromboembolic events, transformation to myelofibrosis and acute myeloid leukemia. Interferon alpha and hydroxyurea are used as first-line treatment for high risk patients. For patients unresponsive to first-line therapy ruxolitinib is available.

Nivolumab belongs to the standard therapy in the second‐line setting of metastatic renal cell carcinoma (mRCC). Although deep and long‐lasting responses are seen in some patients, the majority of patients will further progress. PD‐L1 is still under critical evaluation as a predictive biomarker. Thus, more accurate biomarkers are clearly warranted. Here, we investigated for the first time the predictive role of IDO‐1, a negative immune‐regulatory molecule, on clear cell RCC tissues of 15 patients undergoing nivolumab therapy. IDO‐1 and other immune inhibitory molecules (PD‐L1, PD‐L2, FOXP3) as well as immune cell subsets (CD3, CD4 and CD8) were measured on formalin‐fixed, paraffin‐embedded sections of RCC specimens by immunohistochemistry. IDO‐1 was predominantly expressed in tumor endothelial cells, and was totally absent from tumor cells itself. IDO‐1 overexpression (>10%) could be detected more frequently in responders (100%, n = 6/6) compared to non‐responders (33.3%, n = 3/9; P = .028), resulting in a better progression‐free survival during immunotherapy (IDO‐1 ≤ 10% vs >10%, median: 3.5 vs not estimated (NE) months, P = .01 by log‐rank test). In addition, IDO‐1 was positively correlated with CD8+ T cell expression (r s = .691, P = .006). PD‐L1 expression on tumor cells was negative in 13 (86.7%) of 15 patients, irrespective of therapeutic response (responders vs non‐responders: 83.3% vs 88.9%). No differences were noticed in the PD‐L1 expression on tumor‐infiltrating immune cells (PD‐L1 < 1% in 66.7% of both responders and non‐responders). In contrast to PD‐L1, these results suggest that IDO‐1 may be a more promising predictive biomarker for response to immune‐based cancer therapy in mRCC.

Angiogenesis is a hallmark of cancer and is regulated by a balance of pro- and anti-angiogenic factors; among them, the vascular endothelial growth factor (VEGF) is the key angiogenic factor. VEGF plays an important role in colorectal cancer (CRC) biology, and its inhibition by using bevacizumab, an anti-VEGF antibody, proved for the first time to be effective and became indispensable for the treatment of metastatic CRC (mCRC). Several large phase III studies showed also relevant responses and tolerability of other anti-angiogenic drugs such as ramucirumab, aflibercept, and regorafenib, and led to the approval of these therapeutics. Nevertheless, the efficacy of anti-angiogenic therapies is rather limited and the high expectations raised by preclinical studies were not fulfilled in the clinics. Furthermore, to date, no predictive biomarkers for anti-angiogenic agents could be identified and validated. Thus, new mechanisms of action are discussed, such as tumor vasculature normalization to improve the accessibility of tumor tissue by drugs or to promote tumor infiltration by host immune cells. Cellular and molecular studies will be necessary to characterize the dynamic changes of the tumor microenvironment and the vascular architecture in individual patients in order to predict responsiveness to anti-angiogenic therapies. In this review, we tried to highlight the standard of care of using anti-angiogenics in mCRC patients and to provide an outlook on potential new substances and strategies.

The entity "myelofibrosis" represents a subgroup of the Philadelphia chromosome-negative myeloproliferative neoplasms. It comprises primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. This heterogeneous disease is characterized by clonal myeloproliferation, dysregulated kinase signalling and the abnormal expression of several proinflammatory cytokines. Clinically, patients present with symptoms related to thrombocytosis/leukocytosis, anemia and/or progressive splenomegaly. Mutations in Janus kinase 2, an enzyme that is essential for the normal development of erythrocytes, granulocytes, and platelets, notably the V617F mutation, have been identified in approximately 60% of patients with primary myelofibrosis. Recent molecular advances have not only elucidated critical pathways in the pathogenesis of the disease, but also contributed to a more precise assessment of a patient's individual risk. While allogeneic stem cell transplantation remains the only curative treatment, the natural course of the disease and the patient's survival and quality of life may be improved by new treatments, notably ruxolitinib, the first Janus kinase 1/2 inhibitor approved for the management of myelofibrosis. Additional treatment options are being explored.

Aim: Bone osteoradionecrosis is a serious complication of radiation treatment. Current treatment approaches are not curative and treatment response is often poor leading to high social and healthcare costs. Case report: We report on the first case of osteoradionecrosis with successful restitutio ab integro by repeated administration of platelet gel (PLT-gel) and surgery in a critically ill patient. The administration of PLT-gel during a severe septic episode helped regeneration of bone and soft tissues, shortening the hospital stay of the patient. It was also noted that following applications of PLT-gel, both the use of morphine and the numbers of infective episodes were reduced. Conclusion: Additional studies are needed to confirm the promising effect of PLT-gel for the treatment of osteoradionecrosis.

Over the past decades, considerable progress has been made in the management of colorectal cancer (CRC), leading to a significant improvement in overall survival. Although part of this success has been rightly attributed to aggressive surgical management and advances in other adjunct treatments, our understanding of the pathogenesis of CRC and emergence of newer molecular targets for colon cancer has created a powerful impact. In this review article, we will discuss various targeted therapies in the management of metastatic CRC (mCRC). In particular, vascular endothelial growth factor (VEGF)- and epidermal growth factor receptor (EGFR)-targeting monoclonal antibodies have become integral components of the first-line treatment strategies for mCRC. Newer agents on the horizon soon to be incorporated in clinical practice will be briefly reviewed as well. Currently, the only predictive biomarker for treatment selection in patients with mCRC is tumor RAS mutational status.

The oral Janus associated kinase (JAK1/2) inhibitor ruxolitinib has been available for treatment of patients with intermediate or high-risk myelofibrosis in Europe since 2012. Since its introduction, the expertise of prescribing doctors with respect to ruxolitinib function, efficacy and adverse effects has consistently been augmented, resulting in therapy modalities that are better tailored to individual patients as well as in increased safety of the treatment. The present consensus on ruxolitinib therapy management has been elaborated by Austrian experts in myeloproliferative neoplasms in line with international treatment guidelines. Our recommendations aim to contribute to an improved management of patients with myelofibrosis treated with ruxolitinib.

In this prospective observational single-center study, 55 patients with essential thrombocythemia who were candidates for second line treatment with anagrelide (ANA) received a preliminary cardiovascular (CV) clinical, instrumental and biochemical evaluation (CV history and symptoms, CV risk factors, blood pressure, heart rate, ECG and ECHO-cardio parameters, Troponin I, NT-proBNP). After this in-depth CV screening, 54 out of 55 patients were deemed to be fit for ANA treatment. Thirty-eight of the 55 patients received ANA treatment for a median of 36 months (range 3-48), and were monitored using the same CV evaluation. Fourteen of these 38 patients manifested CV adverse events (10 palpitation, 4 edema, 2 arterial hypertension, 2 acute myocardial infarction) that were not predicted by the in-depth CV evaluation, and that led to ANA withdrawal in only one case (non-cardiac refractory edema). In conclusion, the planned in-depth CV evaluation did not appear to be necessary in ET patients to evaluate their suitability for ANA treatment, and, moreover, was not able to predict the occurrence of CV adverse events during ANA treatment. Nevertheless, the CV adverse events (mostly palpitations and edema) were easily managed by the hematologists, and required the cardiologist involvement in very few selected cases.

We studied the relationships between endothelial extracellular vesicles (EV) and plasminogen-activator inhibitor type 1(PAI-1), to assess their modification in the early phase of sinusoidal obstruction syndrome (SOS). Entry criteria patients who developed SOS at single center from January 2000 to December 2011. Selection patients who underwent hematopoietic stem cell transplantation (HSCT) or actinomicyn-based chemotherapy for nephroblastoma. Participants the study group comprised 5 patients with SOS who were compared with a control group of 7 patients without SOS. Method consecutive blood samples were tested for cell-derived extracellular vescicles (EV), PAI-1 and coagulation parameters. Any statistical significant correlation between all data sets was searched. Results antithrombin level and platelet count were statistically significantly reduced in SOS patients, suggesting a consumption status. PAI-1:Ag and PAI-1:act showed an inverse relationship with platelet counts (coef. -0.034, SE=0.016; P = 0.041 and −0.052, SE=0.019; P = 0.011) respectively. During follow-up PAI-1:Ag was inversely related to EV CD144+ (coef. -0.261, SE=0.094p = 0.007) and antithrombin (coef −0.509, SE=0.175; p = 0.005). PAI-1:act showed an inverse association with EV CD144+ (coef.-0.251, SE=0.121; p = 0.043), EV CD31+/CD41+ (coef. -0.004, SE=0.002; p = 0.026) and antithrombin (coef. -0.470, SE=0.220; p = 0.038). EV generated by rupture of gap junctions (EV CD144+) were increased in SOS patients and showed also a change over time. Conclusions this study demonstrates the existence of an ongoing procoagulant and hypofibrinolytic status in SOS, indicating a possible role for anti-coagulant therapy. Moreover, these findings suggest a role for EV CD 144+ either alone or in combination with PAI-1 as a new biomarker for SOS.

Personalized medicine is rapidly changing the daily routine for the diagnostic work-up and treatment of cancer patients. Several clinical studies and programs are ongoing worldwide to implement personalized anticancer therapies particularly for relapsed/refractory malignancies. On 28 October 2016, the first meeting of the Austrian Expert Panel for Molecular Cancer Profiling was held in Salzburg with the purpose to identify clinical studies and registry programs focusing on comprehensive molecular tumor profiling and personalized cancer therapies in Austria. Representatives of the four Austrian academic centers and from two teaching hospitals were invited to present and debate the current status, challenges, and perspectives in precision oncology. To date, three clinical programs are recruiting patients with relapsed/refractory malignancies in Austria: the ONCO-T-PROFILE program at the Medical University of Innsbruck, the platform MONDTI at the Medical University of Vienna, and the ICT (Individualized Cancer Treatment) phase II trial at the Medical University of Graz. The aim of both research programs and the phase II trial is to investigate the efficacy of molecular profile-based personalized therapies in refractory and relapsed metastatic cancer patients. Furthermore, in cooperation with the AGMT (Study Group of Medical Tumor Therapy), a clinical registry will be established to monitor and to analyze the benefit of molecular profiling in real life.

Background Regulatory T cells (Treg) are critical for cancer immune evasion; whereas natural killer (NK) cells are central for effective anti-tumor immunity including antibody-induced cellular cytotoxicity (ADCC). The predictive role of Treg levels for clinical response to chemo-immunotherapy in non-small cell lung cancer (NSCLC) as well as therapy-induced Treg changes remain to be defined. Patients and methods The impact of Treg on NK-mediated cetuximab-dependent cellular cytoxicity was tested in vitro . Frequency and functional activity of Treg was analyzed in 31 NSCLC stage IB-IIIA patients treated by neoadjuvant Cetuximab/Docetaxel/Cisplatin prior to surgery. Data were correlated with clinical outcome variables and Treg tumor infiltration. Results Treg potently inhibit NK-mediated and cetuximab-induced ADCC in vitro . In addition, a significant correlation between Treg reduction and clinical response was seen. However, the grade of tumor infiltrating Treg in resected tumors did not correlate with peripheral Treg levels. Moreover, Treg levels at diagnosis did not predict clinical response to chemo-immunotherapy. Conclusions The drop of Treg levels during neoadjuvant chemo-immunotherapy in NSCLC patients significantly correlates with clinical response. However, Treg at diagnosis are not linked to inferior clinical response to chemo-immunotherapy in NSCLC in vivo even though Treg efficiently inhibit ADCC in vitro .

Summary The oral Janus associated kinase (JAK1/2) inhibitor ruxolitinib has been available for treatment of patients with intermediate or high-risk myelofibrosis in Europe since 2012. Since its introduction, the expertise of prescribing doctors with respect to ruxolitinib function, efficacy and adverse effects has consistently been augmented, resulting in therapy modalities that are better tailored to individual patients as well as in increased safety of the treatment. The present consensus on ruxolitinib therapy management has been elaborated by Austrian experts in myeloproliferative neoplasms in line with international treatment guidelines. Our recommendations aim to contribute to an improved management of patients with myelofibrosis treated with ruxolitinib.

Qualitativ hochwertige Diagnostik spielt fur die Uberwachung des Therapieerfolgs bei Patienten mit chronisch myeloischer Leukamie eine entscheidende Rolle. Die Verfugbarkeit neuer Tyrosinkinase-Inhibitoren, die zu einem rascheren und tieferen Therapieansprechen fuhren, erfordert den Einsatz standardisierter und hochsensitiver Diagnostikmethoden, um ein optimales Monitoring der Patienten zu gewahrleisten. In der vorliegenden Ubersicht werden die aktuellen internationalen Diagnostikstandards und die zertifizierten Laboratorien in Osterreich prasentiert.

Essential thrombocythemia (ET) patients are at risk of developing thrombotic events. Qualitative platelet (PLT) abnormalities and activation of endothelial cells (ECs) and PLTs are thought to be involved. Microparticles (MPs) can originate from PLTs (PMPs), ECs (EMPs), or red cells (RMPs). Previous studies have indicated that MPs contribute to ET pathophysiology. Endothelial modulators (eg, nitric oxide [NO], adrenomedullin [ADM], and endothelin-1 [ET-1]) are also involved in the pathophysiology of this condition. We hypothesized that treatments for reducing PLT count might also indirectly affect MP generation and endothelial activity by altering endothelial modulator production. The rationale of this study was that hydroxyurea (HU), a cytostatic drug largely used in ET, induces the production of a potent vasoactive agent NO in ECs. An observational retrospective study was designed to investigate the relationship between MPs, NO, ADM, and ET-1 in ET patients on treatment with HU, anagrelide (ANA), aspirin (ASA), and a group of patients before treatment. A total of 63 patients with ET diagnosis: 18 on HU + ASA, 15 on ANA + ASA, 19 on ASA only, and 11 untreated patients, and 18 healthy controls were included in this study. Blood samples were analyzed for MP (absolute total values) and functional markers (percentage values) by flow cytometry. PLT-derived MPs were studied using CD61, CD62P, CD36, and CD63, whereas endothelial-derived MPs were studied using CD105, CD62E, and CD144. Endothelial modulator markers (NO, ADM, and ET-1) were measured by ELISA. Total MP count was higher in the group treated with ANA + ASA (P 0.01). MP markers modified in ET patients returned to levels of healthy controls following treatment, in particular, in patients on ANA treatment. NO and ADM values were higher in the HU group (P 0.001). HU and ANA treatment also affected MP production in a cell origin-specific manner. HU and ANA, although acting via different pathways, have similar final effects. For instance, HU causes vasodilatation by increasing NO and ADM levels, whereas ANA impairs vasoconstriction by reducing ET-1. In conclusion, therapy with HU cytostatic drugs and ANA can reduce PLT count in ET, and also affect endothelial modulatory agents, with HU sustaining vasodilation and prothrombotic MP concentration, whereas ANA decreases vasoconstriction.

OBJECTIVES Although guidelines recommend normalization of platelet counts as an appropriate endpoint for treatment in high-risk essential thrombocythemia (ET), retrospective studies could not prove a correlation of diagnostic platelet counts with an increased thrombotic rate. There is, however, an increasing evidence that leukocytosis is an important risk factor for arterial thrombosis in myeloproliferative neoplasms. METHODS This study considers the Austrian cohort of a European registry regarding the platelet-lowering therapeutic anagrelide. Influence of platelet and white blood cell (WBC) counts on thrombotic risk was assessed. RESULTS Using the calculated cutoffs of 574.5 G/L for platelets and 8.48 G/L for WBC counts, respectively, the Cox regression analysis revealed a clear influence of elevated platelets (P = 0.008) and WBC counts (P = 0.011) on the occurrence of major thrombotic events. The time to a major thrombotic event was shortest (P < 0.001) and the frequency related to 100 patient-years was highest (P =

Chronic wounds, such as diabetic foot ulcers, represent a serious clinical problem for patients and clinicians. Management of these wounds has a strong economic impact worldwide. Complications resulting from injuries are a frequent cause of morbidity and mortality. Chronic wounds lead to infections, painful dressings and prolonged hospitalisation. This results in poor patient Quality of Life and in high healthcare costs. Platelet concentrates (PC) are defined as autologous or allogeneic platelet derivatives with a platelet concentration higher than baseline. PC are widely used in different areas of Regenerative Medicine in order to enhance wound healing processes; they include platelet-rich plasma (PRP), platelet gel (PG), platelet-rich fibrin (PRF), serum eye drops (E-S), and PRP eye drops (E-PRP). This review highlights the use of platelet-rich plasma (PRP) and platelet gel (PG) preparation for clinical use.

Purpose Radioiodine nonavid thyroid cancer (TC) is a rare disease entity with a poor prognosis. Despite a multimodal therapeutic approach including surgery, chemotherapy, and external beam radiation, radioiodine nonavid TC accounts for a high number of TC-associated deaths. The aim of this investigation was to evaluate the response rate of progressive TC patients to treatment with the proteasome inhibitor bortezomib. Materials and methods Seven patients with inoperable, metastasized progressive TC proven to be radioiodine nonavid were included into this pilot study. Patients received bortezomib intravenously with a standardized dose of 1.3 mg/m on days 1, 4, 8, and 11. All patients underwent 3 therapeutic cycles with an interval of 10 days. [F]2-deoxy-2-fluoro-D-glucose positron emission tomography (F-FDG PET) and measurements of thyroglobulin levels were performed before, during, and after therapy, with a 6-week interval to post-therapeutic follow-up. Results Stable disease was seen after proteasome inhibitor therapy in 4 of the 7 patients. Two of the 7 patients showed decrease of maximum standardized uptake value in both post-therapeutic follow-up investigations, and one of these cases also had decreasing thyroglobulin levels. Two patients experienced stable disease during the posttherapeutic follow-up. Two patients showing a mixed response had an improvement in their clinical situation. One patient had rapidly progressive disease, and died 3 months after the last therapeutic cycle. Adverse events included mild polyneuropathy in 2 patients and alterations of the blood count up to WHO (World Health Organization) grade 2 in 5 patients. Conclusion Proteasome inhibitor treatment with bortezomib is a promising therapeutic approach in TC patients without an established treatment alternative. The development of a specific therapeutic regimen for the treatment of radioiodine nonavid TC is warranted.

Immune Thrombocytopenia (ITP) is a rare and - in most patients - mild disease, but might be associated with severe or even life-threatening bleeding complications. The treatment of ITP has partly changed in recent years, due to new therapeutic options. International guidelines changed accordingly. This consensus statement by the Austrian Society of Hematology and Oncology (OEGHO) is not a new evaluation of the current evidence, but rather tries to discuss the available international guidelines and adapt them to the situation in Austria. The subject is primary ITP in adults only. Classification, epidemiology, clinical presentation and diagnostics of ITP, and especially the management of this disease, are discussed in detail. This includes current aspects of first, second, and third line therapies, splenectomy with its indications and contraindications, and the use of new therapeutic options like thrombopoetin receptor agonists (TRA).

HLA class I molecules participate in natural killer cell regulation by acting as ligands for inhibitory killer cell Ig-like receptors (KIRs). One individual may express one or more inhibitory KIR lacking the corresponding HLA ligand. The role of this 'missing KIR ligand' constellation in hematopoietic SCT (HSCT) remains controversial and depends on incompletely defined transplant variables. We have retrospectively analyzed the effects of missing HLA-C group 1/2 and Bw4 KIR ligands in the recipients on the outcome in 382 HSCT, comparing 118 BMT to 264 PBSC transplants (PBSCT). In the multivariate Cox analysis of PBSCT, poor PFS was observed in homozygous HLA-C group 2 (C2/2) recipients (risk ratio (RR), 1.59; P=0.026). In contrast, C2 homozygosity was not unfavorable after BMT (RR, 0.68; P=0.16). C2 homozygous recipients (n=68) had better PFS after BMT than after PBSCT (RR, 0.17; P=0.001), due to fewer relapses (RR, 0.27; P=0.018). Missing Bw4 favorably influenced PFS after BMT (RR, 0.56; P=0.04), but not after PBSCT. These data suggest opposite effects of missing KIR ligands in BMT vs PBSCT. Larger studies are required to reassess whether BMT should be preferred to PBSCT as an option for C2/C2 recipients.

The aim of this study was to investigate the relationship between fungal exposure prior to hospitalisation and ensuing onset of invasive mould infections (IMI) in patients at risk. Patients admitted to the Department of Haematology, Oncology and Transplant Surgery of the Medical University Innsbruck received a questionnaire regarding fungal exposure prior to hospital stay. Questions inquired heavy fungal exposures up to 5 days before hospitalisation. A total of 234 patients were enrolled in this study. Multiple fungus exposures were associated with the onset of community-acquired IMI in patients with haematological malignancies. In univariate analysis, haematological malignancies (P = 0.013) and allergy to dust, pollen or moulds (P = 0.015) were significantly associated with fungal infections. In multivariate analysis, logistic regression showed that haematological patients (P = 0.015) and patients with allergy (P = 0.015) were significantly more frequently infected with fungi. Hospital-independent fungal sources highlight risk-factors for IMI in severe immunocompromised patients and the rate of community-acquired IMI does increase.

BACKGROUND: The objective was to demonstrate feasibility and therapeutic efficacy of routine clinical use of the bendamustine/rituximab combination in lymphoproliferative diseases. PATIENTS AND METHODS: Data were collected retrospectively from 71 patients treated with bendamustine/rituximab combination in Tyrol/Austria. Toxicities, therapeutic response, and survival outcome in the various lymphoma entities were analyzed. RESULTS: There was considerable hematotoxicity, with neutropenia and thrombocytopenia of grade 3 or 4 in 33% and 18%, respectively. Interestingly, severe infection of grade 3 or 4 was observed in a remarkable percentage of patients with aggressive lymphoma and CLL (21% and 28%, respectively) but not in indolent lymphoma (p = 0.027). Overall, the therapeutic efficacy of bendamustine/rituximab was encouraging. In CLL, an overall response rate (ORR) of 65% was achieved. Notably, in the seven previously untreated CLL patients, ORR was 86%. The therapy was effective across all FISH-cytogenetic subgroups, except for the five patients harboring 17p deletion with unfavorable prognosis (PFS 2.7 months, OS 9.3 months). In indolent lymphoma (n = 25), the bendamustine-rituximab combination induced a remarkable therapeutic effect (ORR 96%, median PFS and OS not reached). In aggressive lymphoma (n = 20), ORR was 50%; in International Prognostic Index high-risk patients (4 or 5 risk factors, n = 10), ORR was only 20%, significantly inferior than in low/intermediate risk patients (ORR 70%; p = 0.025). CONCLUSIONS: In the routine setting aside clinical studies, bendamustine/rituximab therapy resulted in marked clinical responses, especially in CLL and indolent lymphoma. In aggressive lymphoma, the combination of bendamustine and rituximab was effective in favorable risk patients.

The success of cancer immunotherapy is limited by potent endogenous immune-evasion mechanisms, which are at least in part mediated by transforming growth factor-β (TGF-β). The E3 ubiquitin ligase Cbl-b is a key regulator of T cell activation and is established to regulate TGF-β sensitivity. cblb-deficient animals reject tumors via CD8(+) T cells, which make Cbl-b an ideal target for improvement of adoptive T-cell transfer (ATC) therapy. In this study, we show that cblb-deficient CD8(+) T cells are hyper-responsive to T-cell receptor (TCR)/CD28-stimulation and are in part protected against the negative cues induced by TGF-β in vitro. Notably, adoptive transfer of polyclonal, non-TCR transgenic cblb-deficient CD8(+) T cells is not sufficient to reject B16-ova or EG7 tumors in vivo. Thus, cblb-deficient ATC requires proper in vivo re-activation by a dendritic cell (DC) vaccine. In strict contrast to ATC monotherapy, this approach delayed tumor outgrowth and significantly increased survival rates, which is paralleled by increased CD8(+) T-cells infiltration to the tumor site and enrichment of ova-specific and interferon-γ (IFN-γ)-secreting CD8(+) T cell in the draining lymph node (LN). Moreover, CD8(+) T cells from cblb-deficient mice vaccinated with the DC vaccine show increased cytolytic activity in vivo. In summary, our data using cblb-deficient polyclonal, non-TCR-transgenic adoptively transferred CD8(+) T cells into immuno-competent non-lymphodepleted recipients suggest that targeting Cbl-b might serve as a novel 'adjuvant approach', suitable to augment the effectiveness of established anti-cancer immunotherapies.

The contribution of natural killer (NK) cells to graft-versus-malignancy (GVM) effects following hematopoietic stem cell transplantation (HSCT) remains uncertain, particularly in the HLA-identical setting. A model considering missing HLA ligands to the donor's inhibitory killer cell immunoglobulin-like receptor (KIR), termed the missing KIR ligand model, has been established in T cell depleted bone marrow transplantation (BMT), but lacks validity in other cohorts with different treatment characteristics. We hypothesized that the impact of missing KIR ligands on relapse-free survival (RFS) and overall survival (OS) in T cell replete peripheral blood SCT (PBSCT) differs from that in the T cell depleted BMT setting, and retrospectively evaluated 100 consecutive, HLA-identical sibling transplantations for hematologic malignancies. In addition to KIR ligand status, we considered the donors' activating KIRs and grafted NK, T, and CD34(+) cell doses. Our findings demonstrate noninferiority for OS (P = .005) and RFS (P = .002) for the heterozygous HLA-C group KIR ligand status (C1/2; n = 47) compared with patients missing either C1 or C2 (n = 53). Similarly, OS (P = .031) and RFS (P = .034) of Bw4-positive patients was noninferior to that of patients missing a Bw4 ligand to KIR3DL1. By multivariate analysis, C1/2 heterozygous patients had a favorable risk ratio (RR) for relapse (RR = 0.28; P = .003), RFS (RR = 0.56; P = .046), and acute graft-versus-host disease grade II-IV (RR = 0.36; P = .05). Following reduced-intensity conditioning (RIC), but not standard-intensity conditioning, myeloablative (MA) transplantation, a grafted NK cell dose above the median (3.4 x 10(7)/kg) was associated with a lower risk of relapse (RR = 0.57; P = .003) and improved survival (RR = 0.78; P = .03). Overall, our findings support a role for NK alloreactivity in HLA-identical HSCT, but argue against a favorable impact of missing KIR ligands in the given setting. We conclude that the mechanism favoring the missing KIR ligand constellation in T cell depleted BMT may not operate in T cell replete PBSCT. The reasons for this differential effect remain unresolved.

The armamentarium of anti-leukemic drugs has increased substantially since anti-leukemic activities were recently found for a variety of non-classical cytostatic drugs, among them the histone deacetylase (HDAC) inhibitor valproic acid (VPA). This study investigated the effect of VPA on proliferation and apoptosis of human Philadelphia chromosome-positive (Ph+) acute lymphatic (ALL) and chronic myeloid leukemia (CML) cells and on colony formation of human chronic-phase CML progenitor cells. Strong anti-proliferative and pro-apoptotic effects of VPA were observed on human ALL and CML cell lines at concentrations achievable in vivo. These effects were most pronounced in ALL cell lines as well as in primary ALL cells. Notably, VPA revealed enhanced activity with imatinib mesylate, nilotinib, the farnesyl transferase inhibitor SCH66336, interferon-alpha and cytosine arabinoside. VPA inhibited the growth of colony-forming cells from 12 Ph+ chronic-phase CML patients but also of those from normal healthy controls in a dose-dependent fashion. HDAC-inhibiting activity of VPA was confirmed on ALL and CML cells. In conclusion, VPA, whether alone or in combination with other non-classical anti-leukemic compounds, exerts significant anti-leukemic effects on human ALL and CML cells.

Invasive fungal infections (IFI) remain a leading cause of morbidity and mortality in immunocompromised patients. This retrospective single-center study analyzed incidence, treatment and outcome of invasive fungal infections in 1,095 patients with hematological malignancies receiving either cytoreductive chemotherapy or autologous or allogeneic hematopoietic stem cell transplantation at our institution between 1995 and 2004. IFI occurred in 167/1,095 (15%) patients with a significant increase over time (12.7% between 1995 and 2000 vs. 18.1% in the later IFI cohort, P = 0.0134). Fifty-four (32%) patients had proven, 70 (42%) patients had probable, and 43 (26%) patients suffered from possible IFI according to EORTC/MSG criteria. In 108/124 (87%) cases with proven or probable IFI, moulds were the causative pathogens. Both, Aspergillus fumigatus (n = 46) and Aspergillus terreus (n = 41) were predominant. Yeast infections (Candida spp.) were documented in 16/124 (10%) cases with proven or probable IFI. Median overall survival of the entire IFI cohort was 7 (3-17) months. Overall survival was significantly better in patients with probable or possible IFI (37 and 38%, respectively) compared with patients with proven IFI (28%, P = 0.019). In 35% of patients, IFI was the principal cause of death with a significant decrease over time (44% in time cohort 1995-2000 vs. 28% in the later IFI cohort, P = 0.018) accompanied by an increased use of novel antifungals. By multivariate analysis, only proven IFI was significantly predictive for death (HR 1.7, P = 0.018). A significant decrease in fungus-related deaths was observed despite a significant increase of IFI over time, probably due to improved diagnostic and therapeutic approaches.

Chronic myeloid leukemia (CML) is a stem cell disease characterized by the BCR/ABL oncoprotein. The ABL kinase inhibitor imatinib is effective in most patients and considered standard first-line therapy. However, not all patients show a long-lasting response to this drug. In fact, resistance against imatinib has been described and is an emerging clinical problem in CML. For these patients, novel multi-kinase inhibitors such as nilotinib or dasatinib as well as stem cell transplantation, represent alternative treatment options. The decision concerning second-line therapies and selection of drugs is usually based on the presence and type of BCR/ABL mutations, the phase of disease, other disease-related factors as well as patient-related factors including age, co-morbidity, and pharmacologic determinants. The current article provides an overview on diagnostic and therapeutic strategies for patients with treatment-naïve and imatinib-resistant CML, together with proposed algorithms that were discussed and approved by members of the CML platform of the Austrian Society for Hematology and Oncology (OGHO) in 2007 and 2008. The resulting recommendations should assist in diagnosis and prognostication in CML, follow-up and disease-monitoring, patient selection for interventional therapies, and in the preparation and conduct of clinical trials.

Objective— In this study, the alternative splicing product of vasohibin 1 (VASH1B) was analyzed in direct comparison to the major isoform (VASH1A) for antiangiogenic effects on endothelial colony forming cells (ECFCs) from peripheral blood and on human umbilical vein endothelial cells (HUVECs). Methods and Results— Expression studies in primary human endothelial cells revealed that both vasohibin proteins, hVASH1A and hVASH1B, localized in the nucleus and cytoplasm. Adenoviruses carrying the cDNA for VASH1A/B and purified recombinant proteins were used to study the function of both molecules in ECFCs and HUVECs. Recombinant VASH1A protein did not inhibit cell proliferation, tube formation, or vessel growth in vivo in the chick chorioallantoic membrane (CAM) assay, but promoted endothelial cell migration in vitro. The VASH1B protein had an inhibitory effect on cell proliferation, migration, tube formation, and inhibited blood vessel formation in the CAM assay. Adenoviral overexpression of VASH1B, but not of VASH1A, resulted in inhibition of endothelial cell growth, migration, and capillary formation. Interestingly, overexpression of VASH1A and B induced apoptosis in proliferating human fibroblasts, but did not affect cell growth of keratinocytes. Conclusion— Our data point out that alternative splicing of the VASH1 pre-mRNA transcript generates a potent antiangiogenic protein.

Objective: In clinical trials, the combination of bortezomib, thalidomide, and dexamethasone (VTD) has shown excellent results as induction treatment in patients with multiple myeloma. However, “real-life” data in unselected Caucasian patients are lacking. Methods: We retrospectively analyzed 41 patients treated with VTD between 2005 and 2014. Results: Post induction, the overall response rate was 78%, with ≥very good partial response (≥VGPR) in 54% and near complete/complete responses (nCR/CR) in 17% of the patients respectively. For patients proceeding to autologous stem cell transplantation (ASCT), post-transplant rates were 96% ≥VGPR and 48% nCR/CR. Median progression free survival (PFS) was 24 months and the estimated 1-year and 2-year overall survival (OS) rates were 95% and 76%, respectively. Subgroup analyses revealed significantly longer OS and PFS in patients with a ≥VGPR as first response status compared to those with a

Anaemia is common in patients with haematologic malignancies. In contrast to solid tumours there are only a few studies exploring anaemia in haematologic cancers. The aim of this study was to determine the prevalence of anaemia (haemoglobin [Hb]12 g/dL) in patients with chronic lymphocytic leukemia (CLL), multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), and Hodgkin's disease (HD) who were scheduled to receive cyclic chemotherapy. Predictive factors for anaemia development and anaemia treatment were also assessed.This prospective chart survey was conducted at 35 oncology centers in Austria. A total of 273 patients were followed through four cycles of nonplatinum chemotherapy, and Hb-levels and anaemia therapy were documented.At baseline, prevalence of anaemia was greatest in patients with MM (77.4%). Prevalence of anaemia increased for all malignancies after cycle 4, with the largest increases noted for patients with NHL (from 35.1% at baseline to 73.7%) and HD (from 21.9% to 54.5%). Cyclic chemotherapy and prior anticancer treatment indicated an increased risk for developing anaemia. Notably, 27.5% of patients with Hb levels10.5 g/dL remained untreated. Transfusions were most often given to patients with severe anaemia (Hb8 g/dL), and erythropoietin most often given to patients with mild or moderate anaemia.Our data confirm that anaemia prevalence in patients with haematologic malignancies is high and increases with chemotherapy. The current practice of anaemia management in these patients leaves room for improvement.

Purpose The identification of malignant cells in effusions by conventional cytology is hampered by its limited sensitivity. The aim of this study was to improve tumor cell detection in effusions by molecular approaches. Materials and Methods A total of 157 effusions from patients with tumors and 72 effusions from patients without a history or evidence of malignancy were included in this study. All effusion specimens were evaluated in parallel by cytology, fluorescence in situ hybridization (FISH) for aneuploidy, and reverse-transcriptase polymerase chain reaction (RT-PCR) for expression of human mammaglobin (hMAM) and mammaglobin B (hMAM-B). Results In effusions from patients with tumors, the sensitivities of tumor cell detection by cytology, FISH, and hMAM and hMAM-B detection were 46.2%, 53.3%, 36.4%, and 57.7%, respectively. The corresponding specificities were 94.4%, 97.0%, 87.1%, and 88.6%. Notably, a high percentage of effusions containing malignant cells were in fact transudates, indicating the necessity for molecular diagnostic work-up of transudates collected from patients with tumors. Dependent on the tumor type, the use of appropriate marker combinations improved tumor cell detection in effusions significantly. By combining all four diagnostic tests, a positive test result indicating the presence of malignancy was achieved in 81.1%, with a fairly good specificity of 70.1%. Conclusion Molecular techniques are definitely useful to detect malignancy in cytologically negative effusions. Tumor cell detection in effusions can be significantly improved by FISH and PCR techniques applying appropriate molecular markers. This finding should help to improve tumor staging, prognostic assessment, and treatment monitoring.

Dendritic cells (DCs) are essential for initiating T-cell responses against either host- or leukaemia-specific antigens. We analysed phenotype, allostimulatory capacity and chimaerism of monocyte-derived DCs (moDCs) serially in 28 patients receiving allogeneic stem cell grafts after conventional myeloablative (n = 14) or reduced-intensity conditioning (RIC, n = 14). Although the recovery of phenotype and function of moDCs after myeloablative stem cell transplantation (SCT) was prompt, there was a trend to a lower expression of co-stimulatory molecules and major histocompatibility antigen class II antigens on mature moDCs in patients who had received RIC transplants. Similarly, the allostimulatory capacity of mature moDCs after RIC transplants was reduced for up to 6 months. Six out of 14 (43%) RIC transplant patients showed a pattern of mixed chimaerism within the first 3 months after transplant. RIC transplant patients with a mixed donor DC chimaerism had a significantly higher risk of relapse (75% versus 35% for patients with full donor DC chimaerism, P = 0.03) but a lower incidence of acute graft-versus-host disease (25% versus 56% for patients with full donor DC chimaerism, P = 0.157). These data, although preliminary, provide evidence that DC function is impaired after RIC transplants and that DC chimaerism may have an impact on graft-versus-host and graft-versus-leukaemia reactions.

A major goal of experimental and clinical hematology is the identification of mechanisms and conditions supporting the expansion of transplantable hematopoietic stem cells. We assessed the expansion potential of CD34+CD71-CD45- cells derived from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood under recently defined serum-free culture conditions. The CD34+CD71-CD45- cells in mobilized peripheral blood were found to contain the majority (92%+/-5.6) of primitive long-term culture initiating cells (LTCIC) and 53.5%+/-16.7 of the more committed colony-forming cells (CFC). Furthermore, this population represents 23.3%+/-4.1 of the total CD34+ cells and allows reduction of the cell density important for maintenance/expansion of primitive progenitor cells. CD34+ CD71- CD45- cells were cultured in defined serum-free media supplemented with 300 ng each of Flt-3 ligand and stem cell factor (SCF), 60 ng of interleukin (IL)-3, and 20 ng each of IL-6 and G-CSF. Mononuclear cells (MNC) and CFC were expanded 50-fold and 200-fold, respectively; primitive progenitor cells (LTC-IC) were maintained at input values after a total of 10 days of expansion. The addition of IL-15 to our cytokine cocktail expanded LTC-IC 2- to 3-fold and CFC to500-fold. The data presented should allow clinical manipulation (purging) and expansion procedures with mobilized PBPC harvests without the loss of primitive progenitor cells and could be made applicable for large-scale clinical expansion.

Summary. Donor lymphocyte infusions (DLI) can induce a graft-versus-leukaemia (GvL) reaction in patients with relapsed disease. However, the mechanisms involved in remission induction are not completely known. A patient with chemotherapy-refractory relapse 1 year after human leucocyte antigen (HLA)-identical, unrelated stem cell transplantation (SCT) for bcr/abl-positive common acute lymphoblastic leukaemia (ALL) received a DLI from the original donor, and achieved complete cytogenetic and molecular remission concomitantly with extensive graft-versus-host disease (GvHD). Seven CD8+, donor-derived, alloreactive T-cell clones were generated by stimulating post-DLI remission cells with the patient's pretransplant mature dendritic cells. The minor histocompatibility antigen (mHag) recognized by these T-cell clones was identified as HA-1, a mHag associated with acute GvHD after SCT. Our finding provides evidence of HA-1-associated GvL effects after DLI that paralleled the eradication of full-blown, chemotherapy-refractory ALL relapse after allogeneic SCT.

The objective of this study was to analyze the mobilization kinetics of normal (BCR-ABL(neg)) and malignant (BCR-ABL(pos)) progenitor cells using a new, low toxic, out-patient-based mobilization regimen for Philadelphia chromosome-positive (Ph(pos)) chronic myelogenous leukemia (CML) patients. High doses of hydroxyurea (HD-HU, 3.5 g/m(2) per day, orally for 7 days) followed by granulocyte colony-stimulating factor (G-CSF) (10 microg/kg subcutaneously) were administered to 11 newly diagnosed CML patients. Each apheresis product (n = 30) was individually analyzed for the number and genotype of mature colony-forming cells (CFC) and primitive long-term culture initiating cells (LTC-IC), respectively, by reverse transcription polymerase chain reaction (RT-PCR) of individual colonies. Sufficient numbers of CD34(+) cells/kg bodyweight (BW) could easily be obtained in all patients (median, 15 x 10(6)/kg BW per patient) with a median number of three aphereses performed per patient (range 2-4). Almost each apheresis itself (25/30) contained > or =2 x 10(6) CD34(+) cells/kg BW. All patients with low and intermediate Sokal risk indices (9/11) mobilized primarily BCR-ABL(neg) LTC-IC (median 92%, range 47-100) and CFC (median 89%, range 57-100). Moreover, the mean percentage of BCR-ABL(neg) CFC and LTC-IC in the various apheresis products in these patients did not change throughout the entire time of hematopoietic regeneration. The toxicity of the mobilization procedure was low. Side effects were mild erythema in 8/11 and oral mucositis in 3/11 patients. Overall, the low toxicity of this regimen, together with the fact that sufficient BCR-ABL(neg) progenitors can be collected throughout the entire period of hematopoietic regeneration, renders this mobilization regimen particularly attractive for the collection of BCR-ABL(neg) progenitors in early chronic phase of Ph(pos) CML.

To assess the frequency and prognostic impact of Ep-CAM and Her-2/neu overexpression in patients with breast cancer and to determine its relationship with other prognostic markers, 205 breast cancer patients with a median follow-up of 10.8 years were enrolled in this retrospective study. Overexpression of Ep-CAM and Her-2/neu in tumor tissue samples was assessed by immunohistochemistry. Tumors presenting a Her-2/neu 2+ staining were additionally analyzed by FISH to exclude false positive results. Ep-CAM and Her-2/neu overexpression was found in 35.6% and 19.5% of the tumor samples, respectively. Both Ep-CAM and Her-2/neu overexpression were predictive for poor disease-free (DFS) and disease-related overall survival (DROS). Concurrent Ep-CAM and Her-2/neu overexpression was present in 13.2% of tumor specimens and had an additive negative impact on DFS and DROS. This minority of patients had a median time to relapse of only 34 months, whereas the median time to relapse was not reached in the patient population without Her-2/neu and Ep-CAM overexpression. By multivariate analysis Ep-CAM overexpression proved to be an indicator of poor prognosis, independent of tumor size, histologic grade, hormone receptor expression and Her-2/neu overexpression. In conclusion, overexpression of Ep-CAM and Her-2/neu complement each other as predictors for poor prognosis in patients with invasive breast cancer. Determination of these tumor markers should help in assigning breast cancer patients to 1 of 3 distinct risk categories.

The formation of new blood vessels is essential for the growth of malignant tumors and their hematogenic spread. Tumor-induced neoangiogenesis occurs through sprouting of preexisting vessels. An alternative mechanism might be the recruitment of bone marrow-derived endothelial cells, or their precursors, to the tumor site by the release of vascular endothelial growth factor (VEGF) from cancer cells, i.e., tumor-induced postnatal vasculogenesis. To investigate if a significant amount of VEGF is released from malignant tumors in vivo, thus potentially mobilizing endothelial precursor cells (EPC) from the bone marrow, we measured plasma levels of soluble VEGF obtained from tumor-draining mesenteric veins (VEGF-M) during surgery and, simultaneously, in venous blood obtained distant from the tumor (VEGF-P). This analysis was performed in 29 patients with colorectal carcinoma. VEGF-M levels were substantially higher in patients with distant metastases (208 ± 61 pg/ml) compared to patients with nonmetastatic disease (99 ± 72 pg/ml, p = 0.003). Also, in patients with aggressive disease, i.e., histologically undifferentiated (G3) tumors, higher levels of VEGF-M were measured than in patients with tumors of lower histologic grading (196 ± 46 vs. 107 ± 80 pg/ml, p = 0.01). In conclusion, the release of significant amounts of soluble VEGF in vivo from clinically and/or histologically aggressive tumors might reflect their high angiogenic or vasculogenic potential, probably leading to the recruitment of EPC from the bone marrow.

To the editor: Follicular lymphoma in situ (FLIS) is characterized by the presence of a B-cell population with immunophenotypic and genotypic features of follicular lymphoma (FL) but exclusively localized to germinal centers (GCs) in morphologically reactive lymph nodes.[1][1] FLIS lesions are

Several tyrosine kinase inhibitors (TKIs) are approved for chronic myeloid leukemia (CML) therapy. We evaluated the long-term cost-effectiveness of seven sequential therapy regimens for CML in Austria. A cost-effectiveness analysis was performed using a state-transition Markov model. As model parameters, we used published trial data, clinical, epidemiological and economic data from the Austrian CML registry and national databases. We performed a cohort simulation over a life-long time-horizon from a societal perspective. Nilotinib without second-line TKI yielded an incremental cost-utility ratio of 121,400 €/quality-adjusted life year (QALY) compared to imatinib without second-line TKI after imatinib failure. Imatinib followed by nilotinib after failure resulted in 131,100 €/QALY compared to nilotinib without second-line TKI. Nilotinib followed by dasatinib yielded 152,400 €/QALY compared to imatinib followed by nilotinib after failure. Remaining strategies were dominated. The sequential application of TKIs is standard-of-care, and thus, our analysis points toward imatinib followed by nilotinib as the most cost-effective strategy.

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 × 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 × 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings.

Purpose The purpose of this study was to provide a clinician-friendly overview of decision-analytic models evaluating different treatment strategies for multiple myeloma (MM). Methods We performed a systematic literature search to identify studies evaluating MM treatment strategies using mathematical decision-analytic models. We included studies that were published as full-text articles in English, and assessed relevant clinical endpoints, and summarized methodological characteristics (e.g., modeling approaches, simulation techniques, health outcomes, perspectives). Results Eleven decision-analytic modeling studies met our inclusion criteria. Five different modeling approaches were adopted: decision-tree modeling, Markov state-transition modeling, discrete event simulation, partitioned-survival analysis and area-under-the-curve modeling. Health outcomes included survival, number-needed-to-treat, life expectancy, and quality-adjusted life years. Evaluated treatment strategies included novel agent-based combination therapies, stem cell transplantation and supportive measures. Conclusion Overall, our review provides a comprehensive summary of modeling studies assessing treatment of MM and highlights decision-analytic modeling as an important tool for health policy decision making.

Sensitive screening for Aspergillus spp. using polymerase chain reaction (PCR) of whole blood samples in patients with haematological disorders has not been performed to date. In a 2-year study, 121 patients admitted to the University Hospital of Innsbruck for cancer chemotherapy without clinical signs of fungal infection were prospectively screened for Aspergillus spp. In 28 out of 121 (23%) patients, Aspergillus DNAaemia was detected. Of these patients, 16 (57%) were positive only once for Aspergillus DNA, but positivity was never associated with invasive aspergillosis. PCR positive episodes were short and resolved without antifungal treatment. Five patients (18%) had intermittent PCR positive results. Seven (25%) patients presented at least two consecutive positive PCR results; one of these patients developed invasive aspergillosis and another two were strongly suspected as having aspergillosis. Based on the criteria of the European Organization for Research and Treatment of Cancer case definitions, sensitivity and specificity of serial PCR monitoring were 75% and 96%. Positive PCR results became negative shortly after commencement of antifungal treatment, but the changes did not correlate with clinical responsiveness to treatment in three patients. Our results indicate the potential usefulness of PCR for screening for Aspergillus spp. in patients at risk, but without antifungal treatment.