Search

The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients. However, ongoing epidemiological changes and rise of new virus variants require repeated revisions and adaptations of prophylaxis and treatment strategies to meet these new challenges. Therefore, this guideline provides an update on evidence-based recommendations with regard to vaccination, pharmacological prophylaxis and treatment of COVID-19 in cancer patients in light of the currently dominant omicron variants. It was developed by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) based on a critical review of the most recent available data., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients with cancer are at particular risk for infection but also have diminished vaccine responses, usually quantified by the level of specific antibodies. Nonetheless, vaccines are specifically recommended in this vulnerable patient group. Here, we discuss the cellular part of the vaccine response in patients with cancer. We summarize the experience with vaccines prior to and during the SARS-CoV-2 pandemic in different subgroups, and we discuss why, especially in patients with cancer, T cells may be the more reliable correlate of protection. Finally, we provide a brief outlook on options to improve the cellular response to vaccines.

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.

Antifungal posaconazole prophylaxis for AML patients receiving induction chemotherapy has been routine at our centre since 2009. This retrospective study examined the feasibility and practicability of our prophylaxis guidelines in clinical practice. Data sets of 90 patients undergoing induction-chemotherapy for AML between 2011 and 2014 were evaluated regarding adherence to local guidelines for the administration of antifungal prophylaxis with posaconazole. 75.5% of the 90 patients received posaconazole prophylaxis. All but eight patients received the recommended dosage. A total of 77.95% on prophylaxis had serum galactomannan measured twice weekly. Contradicting our guidelines, 89.70% of patients received concomitant therapy with PPI. Overall, 16.17% of patients had prophylaxis discontinued and started empirical antifungal treatment in the absence of diagnostic criteria for IFI. The breakthrough IFI rate was 36.76% (proven, probable and possible) with 7.35% of infections being classified as proven or probable. Although limited by a small sample size, our study demonstrates the feasibility of local guidelines in a real life setting and outlines areas for improvement in both guidelines and clinical practice. We also highlight the importance of ensuring awareness of guidelines and raise questions about a uniform approach to antifungal prophylaxis in AML patients., (© 2017 Blackwell Verlag GmbH.)

Purpose: BK-virus and JC-virus are the most common polyomaviridae associated with hemorrhagic cystitis in the allogeneic transplant setting. Hemorrhagic cystitis and symptomatic viruria caused by these viruses are a major cause of morbidity in patients undergoing allogeneic stem cell transplantation., Methods: We performed a retrospective evaluation on a highly uniform study population of 73 patients receiving allogeneic stem cell transplantation. Patients were treated according to the FLAMSA-RIC-protocol, and were examined for the incidence of BK-/JC-viruria and late-onset BK-positive hemorrhagic cystitis within a two-year period., Results: The occurrence of BK-viruria was correlated with published risk factors (acute GvHD, oral mucositis, donor type, conditioning, age, gender). Thirty patients (41 %) were found to excrete either BK-virus (n = 17), JC-virus (n = 3) or both (n = 10), of whom 18 patients (60 %) developed higher-grade hemorrhagic cystitis as opposed to none in the virus-negative control group. Higher grade GvHD (grade B-D) was more common in patients with viruria (p = 0.013) and also more common in patients with manifest hemorrhagic cystitis (p = 0.048). Similarly, oral mucositis was associated both with viruria (p = 0.014) and hemorrhagic cystitis (p = 0.005). Manifest cystitis but not viruria was significantly associated with male gender (p = 0.016). No significant correlation was found with age, conditioning with busulfane vs total body irradiation or related vs unrelated donor., Conclusions: Severe GvHD and oral mucositis are significantly associated with reactivation of polyomaviridae in the genitourinary-tract already at the level of asymptomatic viruria.

Reduced oxygen partial pressure (pO2) has been recognized as being relevant in hematopoiesis and the pathophysiology of malignant diseases. Although hypoxic (meaning insufficient supply of oxygen) and anoxic areas are present and of pathophysiologic importance (by hypoxia-induced pathways such as HiF1α) in solid tumors, this may not be true for (malignant) hematologic cells. Hematopoiesis occurs in the stem cell niche, which is characterized, among other things, by extremely low pO2. However, in contrast to solid tumors, in this context, the low pO2 is physiological and this feature, among others, is shared by the malignant stem cell niche harboring leukemia-initiating cells. Upon differentiation, hematopoietic cells are constantly exposed to changes in pO2 as they travel throughout the human body and encounter arterial and venous blood and migrate into oxygen-carrier-free tissue with low pO2. Hematologic malignancies such as acute myeloid leukemia (AML) make little difference in this respect and, whereas low oxygen is the usual environment of AML cells, recent evidence suggests no role for real hypoxia. Although there is no evidence that AML pathophysiology is related to hypoxia, leukemic blasts still show several distinct biological features when exposed to reduced pO2: they down- or upregulate membrane receptors such as CXCR4 or FLT3, activate or inhibit intracellular signaling pathways such as PI3K, and specifically secrete cytokines (IL-8). In summary, reduced pO2 should not be mistaken for hypoxia (nor should it be so called), and it does not automatically induce hypoxia-response mechanisms; therefore, a strict distinction should be made between physiologically low pO2 (physoxia) and hypoxia., (Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.)

Purpose: Weight loss in cancer patients has been attributed with significant morbidity and mortality. During allogeneic stem cell transplantation (SCT), oral nutrition is often hampered and hence total parenteral nutrition (TPN) is necessary. We therefore investigated the course of weight during stem cell transplantation and the clinical consequences of weight change., Methods: 180 consecutive patients who received allogeneic SCT between January 2010 and December 2011 at our center were analyzed for weight loss, laboratory and clinical parameters., Results: During SCT, a median decrease of 6.6% of body mass index (BMI) was observed for the whole population (from 25.3 at admission to 23.6 at discharge), and a 1.6fold increase of malnutrition despite use of TPN (28.3% to 45.0%). 55.6% of patients experienced a significant weight loss of ≥5% with a median decrease of 9.2% in BMI. Serum levels of albumin, total protein and cholesterol rapidly decreased during conditioning therapy. After a median of 2.4 years, the median BMI was still only 23.4 (not different from discharge). However, we did not observe a meaningful difference in side effects and survival between patients that did or did not lose weight., Conclusion: Weight loss is commonly observed during allogeneic SCT despite TPN, but the clinical consequences thereof seem limited: we observed no significant impact on patients with a decrease ≥ 5% in BMI on transplant outcome, side effects or survival.

We retrospectively compared the incidence of virus infections and outcome in the context of immune reconstitution in two different HLA-haploidentical transplantation (haplo-HSCT) settings. The first was a combined T-cell-replete and T-cell-deplete approach using antithymocyte globulin (ATG) prior to transplantation in patients with hematological diseases (cTCR/TCD group, 28 patients; median age 31 years). The second was a T-cell-replete (TCR) approach using high-dose posttransplantation cyclophosphamide (TCR/PTCY group, 27 patients; median age 43 years). The incidence of herpesvirus infection was markedly lower in the TCR/PTCY (22 %) than in the cTCR/TCD group (93 %). Recovery of CD4+ T cells on day +100 was faster in the TCR/PTCY group. CMV reactivation was 30 % in the TCR/PTCY compared to 57 % in the cTCR/TCD group, and control with antiviral treatment was superior after TCR/PTCY transplantation (100 vs 50 % cTCR/TCD). Twenty-five percent of the patients in the cTCR/TCD group but no patient in the TCR/PTCY group developed PTLD. While 1-year OS was not different (TCR/PTCY 59 % vs cTCR/TCD 39 %; p = 0.28), virus infection-related mortality (VIRM) was significantly lower after TCR/PTCY transplantation (1-year VIRM, 0 % TCR/PTCY vs 29 % cTCR/TCD; p = 0.009). On day +100, predictors of better OS were lymphocytes >300/μl, CD3+ T cells >200/μl, and CD4+ T cells >150/μl, whereas the application of steroids >1 mg/kg was correlated with worse outcome. Our results suggest that by presumably preserving antiviral immunity and allowing fast immune recovery of CD4+ T cells, the TCR approach using posttransplantation cyclophosphamide is well suited to handle the important issue of herpesvirus infection after haplo-HSCT.

Background: Miliary brain metastases are a rare condition but associated with an exceedingly poor prognosis. We present the case of a patient suffering from malignant melanoma with an acute progressively worsening of neurological symptoms up to the loss of consciousness. The magnetic resonance imaging (MRI) demonstrated a new onset of disseminated, miliary spread of central nervous system metastases from a malignant melanoma within 4 days., Case Presentation: We report on a 57-year-old woman suffering from metastatic malignant melanoma positive for BRAF-V600E mutation who developed an acute onset of neurological symptoms. The patient received vemurafenib and dacarbacin as chemotherapeutic regime for treatment of malignant melanoma. After admission to our hospital due to progressive disturbance of memory and speech difficulty a magnetic resonance tomography (MRI) was performed. This showed no evidence of cerebral tumour manifestation. The symptoms progressed until a loss of consciousness occurred on day five after admission and the patient was admitted to our intensive care unit for orotracheal intubation. No evidence for infectious, metabolic or autoimmune cerebral disorders was found. Due to the inexplicable acute worsening of the neurological symptoms a second MRI was performed on day five. This revealed a new onset of innumerable contrast-enhancing miliary lesions, especially in the grey matter which was proven as metastases from malignant melanoma on histopathology., Conclusion: This case describes an unique hyperacute onset of tumour progression correlating with an acute deterioration of neurological symptoms in a patient suffering from miliary brain metastasis from BRAF positive malignant melanoma.

Brentuximab Vedotin is an antibody - drug conjugate targeting CD30. We report a case of severe cytokine release syndrome (CRS) after administration of the first dose of Brentuximab Vedotin in a 64-yr-old patient with relapsed systemic anaplastic large cell lymphoma (sALCL). To our knowledge, this is the first case of CRS to Brentuximab Vedotin described in the literature. However, CRS to Brentuximab Vedotin might be underestimated, as the drug has not been tested in large phase III trials yet., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Invasive fungal disease (IFD) is a feared complication in patients with hematological malignancies. In 2008, the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG) published updated criteria for the diagnostic workup within clinical studies for immunosuppressed patients with suspected fungal infection. We applied these criteria in a routine clinical setting with regard to their feasibility for bedside practice at our institution in a 1-year period. One hundred seventy consecutive patients with a recent history of chemotherapy-induced neutropenia (n = 100) or allogeneic stem cell recipients (n = 70) who had received a CT scan of the chest in search of pulmonary IFD were examined. We analyzed all available radiological and microbiological data according to the EORTC/MSG criteria. The quality of images was good in 94.7%, microbiological diagnostics performed in 94.1% patients. Five patients had histopathologic-proven IFD, 18 patients were classified as "probable," 55 patients as "possible" IFD, and 92 patients did not fulfill any criteria ("no IFD"). Microbiology revealed suggestive findings in 29 patients. These were either galactomannan antigen (Gm-AG) in serum (n = 18) and/or broncho-alveolar lavage (BAL) (n = 5). CT scan showed pulmonary infiltrates in 106 patients; 78 were classified as typical for IPA, further discriminated by morphology and number of nodules, as well as additional signs (halo, air crescent, cavity). We observed a better overall survival in patients without infiltrates compared to those with any type of infiltrate (p = 0.042) and a trend toward favorable survival in patients who had micronodular lesions (p = 0.058). We also found a higher probability of Gm-AG positivity in the group of allogeneic stem cell transplantation (allo-SCT) patients (p = 0.001) and a trend toward an association of Gm-AG positivity and positive findings on CT (p = 0.054). The applicability of criteria was good, both with regard to radiological and mycological evidence and sufficient for the categorization of IFD according to EORTC/MSG in the clinical setting. However, our findings suggest that feasibility improves with stringency of mycological workup, which is reflected in the two subgroups. Radiology harvests by far more suggestive findings which can only partly be correlated with mycological evidence. Although feasible, whether the EORTC/MSG criteria are the appropriate tool for early identification of IFD remains open for discussion.

Prognosis is poor for patients with biologically aggressive Non-Hodgkin lymphoma (NHL), refractory to chemotherapy or relapsed after autologous transplantation, especially when no disease control before allogeneic transplantation is achieved. In 16 patients (median age 53, median prior regimes 5) with relapsed or refractory non-remission NHL, we analysed retrospectively the efficacy of a sequential therapy comprising clofarabine re-induction followed by a reduced-intensity conditioning with fludarabine, CY and melphalan, and T-cell-replete HLA-haploidentical transplantation. High-dose CY was utilized post-transplantation. All patients engrafted. Early response (day +30) was achieved in 94%. Treatment-related grade III-IV toxicity occurred in 56%, most commonly transient elevation of transaminases (36%), while there was a low incidence of infections (19% CMV reactivation, 19% invasive fungal infection) and GVHD (GVHD: acute III-IV: 6%; mild chronic: 25%). One-year non-relapse mortality was 19%. After a median follow-up of 21 months, estimated 1- and 2-year PFS was 56 and 50%, respectively, with 11 patients (69%) still alive after 2 years. In summary, sequential therapy is feasible and effective and provides an acceptable toxicity profile in high-risk non-remission NHL. Presumably, cytotoxic reinduction with clofarabine provides enough remission time for the graft-versus lymphoma effect of HLA-haploidentical transplantation to kick in, even in lymphomas that are otherwise chemo-refractory.

Haploidentical haematopoietic SCT (HSCT) using T-cell-replete grafts and post-transplant high-dose CY has found increasing acceptance. Our purpose was to evaluate the feasibility and outcome of this strategy as second HSCT incorporating donor change for acute leukaemia relapse after a first allogeneic transplantation. The courses of 20 consecutive adults (median age 37 years, 12 male) with AML (n=14), ALL (n=5) and acute bi-phenotypic leukaemia (n=1) were analysed retrospectively. Conditioning consisted of fludarabine, CY and either melphalan or TBI or tresosulfan+/-etoposide. Engraftment was achieved in 17 (85%), and a second remission was induced in 15 patients (75%) on day +30. The rate of grade II-IV acute GvHD was 35%, while chronic GvHD occurred in five patients. Most commonly observed grade III-IV toxicities were mucositis (30%), hyperbilirubinemia (20%), elevation of transaminases (20%) and creatinine (20%), while invasive fungal infection affected 30%. One-year non-relapse mortality (NRM) was 36%. At a median follow-up of 17 months, estimated 1-year OS was 45%, and 1-year relapse-free survival was 33%. This strategy was feasible and allowed for successful engraftment with a moderate rate of toxicity. Early outcome and NRM are at least comparable with results after a second HSCT from HLA-matched donors without donor change at HSCT2.

Since two large-scale, randomised studies on posaconazole prophylaxis have demonstrated a clear benefit for patients at high risk for contracting invasive fungal disease (IFD), posaconazole prophylaxis has been adopted as standard of care for this patient collective. Several years on from implementation at our institution, we wanted to evaluate its impact on the incidence and use of empirical antifungal therapy in a real-life setting. We analysed retrospectively incidence and severity of IFD in high-risk patients with prophylaxis, using a historical cohort as comparator. A total of 200 patients had either received the extended spectrum triazole posaconazole in prophylactic dosage of 200 mg tid or empirical antifungal therapy. Disease events were analysed by application of the revised EORTC/MSG definitions for IFD. Before posaconazole prophylaxis, we recorded 57/100 cases of IFD which was reduced to 28/100 with prophylaxis. The empirical use of antifungal drugs was reduced to 41% from 91% in the non-prophylaxis cohort. Furthermore, we observed a shift in the categorisation of IFD according to EORTC/MSG criteria. Our data suggest that posaconazole was effective in reducing the rate and probability of invasive fungal disease in high-risk patients., (© 2013 Blackwell Verlag GmbH.)

Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider's perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were €51,517 in the IFD group and €30,454 in the control group. Incremental costs of €21,063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons., (© 2012 Blackwell Verlag GmbH.)

Invasive fungal diseases (IFD) are a major cause of morbidity and mortality in patients with acute myeloid leukaemia (AML). Their incidence has risen dramatically in recent years. The diagnosis of IFDs remains difficult, even if the European Organisation for the Research and Treatment of Cancer (EORTC)/Mycosis Study Group (MSG) criteria are applied for study purposes to classify the likelihood of these infections. These criteria have been developed for clinical trials, and their relevance in clinical settings outside a clinical trial remains unknown. We evaluated the impact of the EORTC/MSG criteria and a modification thereof for clinical purposes in patients with AML. We retro-spectively analysed 100 AML patients for the occurrence of IFD. First, EORTC/MSG criteria were applied to classify the patients. Second, a modified version of these criteria already used in clinical trials was used to re-classify the patients. Fifty-seven patients developed an invasive fungal infection. Following the original criteria, 43% were classified as 'possible' IFD, whereas 7% each were classified as 'probable' and 'proven' IFD. After application of the modified criteria, only 9% of the patients remained 'possible' IFD, whereas 41% were 'probable'. The occurrence of 'proven' cases was not altered by the modification and thus remained 7%. The application of modified criteria for the classification of IFD in AML patients leads to a considerable shift from 'possible' IFD (according to conventional EORTC criteria) towards 'probable' IFD. Nevertheless, neither the old EORTC criteria nor their modification was designed for use in clinical practice. As this study underscores the uncertainty in the diagnosis of IFD, the need for a clinically applicable classification is obvious., (© 2010 Blackwell Verlag GmbH.)

Fever is a common symptom in patients with malignancies. On the one hand it may be an (initial) symptom of cancer, on the other hand it may occur as a side effect of chemotherapy. Often a precise cause of fever can not be established and in these cases febrile temperatures >38.3 degrees C without proof of infection or relapse/progress of tumor is defined as fever of unknown origin. Especially hematologic neoplasias are accompanied by fever. Here, neoplastic fever must be distinguished from fever following immunosuppressive chemotherapy. In the latter severe infections due to neutropenia induced by cytoreductive chemotherapy is often identified as the cause of fever. These patients display a high morbidity and mortality, especially if an empiric anti-infectious treatment is not administered in time. A meticulous diagnostic work-up is therefore necessary, and until proven otherwise, an infectious cause must be considered and empiric antibiotic treatment initiated.

Background: Bacterial, viral, and fungal pathogens frequently cause severe, life-threatening infections in immunocompromised patients after allogeneic hematopoietic stem cell transplantation (SCT)., Objective: To compare the frequency of infections in patients with matched-related (Group A) or with human leukocyte antigen (HLA)-matched-unrelated donors (Group B)., Patients and Methods: Patients treated at our transplantation unit between April 2004 and April 2005 were enrolled into this analysis. Documentation comprised demographic data, conditioning treatment, stem cell source, clinical course, as well as microbiological and clinical data and mortality., Results: We analyzed 59 patients, 22 in Group A and 37 in Group B. Both groups were well balanced regarding demographic data. Diagnoses were acute myeloid leukemia (30 of 59 patients, 50.8%), multiple myeloma (15.2%), acute lymphoblastic leukemia (11.9%), and chronic myeloid leukemia (10.2%). Patients in Group A developed infections in 95.5% of the cases compared with 97.3% in patients in Group B. Most frequently detected pathogens were Staphylococcus species, human herpesvirus-6, and Epstein-Barr virus. Three proven fungal infections were detected in Group A compared with 9 proven fungal infections in Group B. Lung infiltrations were observed in equivalent incidence in both groups. Two years after transplantation, 55.9% of patients were alive (Group A: 68.2%; Group B: 48.6%, not significant)., Conclusion: Allogeneic SCT from HLA-matched-unrelated donors does not have a higher infection risk than patients transplanted from matched-related donors.

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in patients with haematological malignancies. Antifungal combination therapy is a promising treatment option. However, available data on feasibility, toxicity and efficacy of this therapy are limited. Therefore, this study was conducted to evaluate the feasibility, toxicity and outcome of different antifungal combination therapies. Patients with haematological malignancies receiving antifungal combination therapy for IFI were retrospectively analysed. Toxicity and response were documented at the end of therapy. Survival was evaluated at the end of therapy and after 12 weeks. Fifty-six patients were treated with different antifungal combinations in the period between 2001 and 2007. The majority of patients (63%) received a combination of liposomal amphotericin B and caspofungin as antifungal combination treatment. Toxicity of all applied combinations was tolerable. At the end of combination therapy, favourable response was 65%, whereas unfavourable outcome occurred in 35% of the cases. Mortality at the end of treatment was 11% and 34% 3 months after initiation of combination therapy. Antifungal combination therapy is feasible and efficient in haematological cancer patients and allogeneic stem cell transplant recipients with IFI. Prospective studies to evaluate the optimal combinations are needed.

Neutropenic patients are at high risk to develop invasive fungal infections (IFI). Immediate antifungal treatment has been considered necessary for the treatment of these patients. However, only a minority of patients have 'probable' or 'proven' IFI according to EORTC-/MSG-criteria. The majority of the patients present with ongoing fever in neutropenia or 'possible' IFI only. To date, two treatment strategies are used for patients with fever in neutropenia and suspected IFI: empirical or preemptive antifungal therapy. Both regimens are discussed controversially as there is no clear evidence as to which strategy is superior. Empirical treatment bears the danger of 'overtreatment' with potentially toxic and expensive drugs, whereas preemptive therapy may sometimes be initiated too late to work efficiently against fungal disease. This article reviews both treatment options and discusses advantages and draw-backs of either strategy.

Background: Activity and efficacy of liposomal amphotericin B have been established for the treatment of severe fungal infections. Nephrotoxic side effects, especially during prolonged administration, are regarded as a major disadvantage. In this study we examined the response rates and side effects, particularly nephrotoxicity, of treatment with liposomal amphotericin B in a large cohort of patients., Patients and Methods: 406 patients treated with liposomal amphotericin B between January 1999 and August 2003 in participating German hospitals were included. Documentation included demographic and clinical data, reason for the treatment with liposomal amphotericin B, length of treatment, response to antifungal treatment and side effects., Results: 42.4% of the 406 patients were females. Their ages ranged from 1 day to 77 years. 83 % of the patients had malignancies and 65.5 % had fever of unknown origin (FUO). Mean duration of treatment with liposomal amphotericin B was 20 +/- 20 days, at an average dose of 2.3 mg/kg/d. 209 patients (51.5 %) showed complete response (CR),105 patients (25.9 %) partial response (PR) and 51 (12.6 %) patients died during the observation. 80.0 % of patients with FUO showed complete or partial response of symptoms. Mean serum creatinine increased from 0.9 mg/kg before start of therapy with liposomal amphotericin B to 1.1 mg/kg during treatment. Side effects (common toxicity criteria > grade 1) occurred in 94 patients (23/2 %). Among these hypokalemia (6.2 %) and liver damage (5,2 %) were the most common. Nephrotoxicity was documented in 17 patients (4.2 %)., Conclusion: Liposomal amphotericin B is a safe and efficacious antifungal drug in the treatment of severe invasive fungal infections and fever of unknown origin. Nephrotoxicity is usually not a limiting factor when using liposomal amphotericin B, if it is administered in approved dosage.

Purpose: To compare parallel acquisition magnetic resonance (MR) imaging with thin-section helical computed tomography (CT) for depiction of pulmonary abnormalities suggestive of pneumonia in immunocompromised patients., Materials and Methods: The institutional review board approved this study; prior consent was obtained. Thirty consecutive neutropenic patients (10 women, 20 men; mean age, 51 years +/- 15 [standard deviation]; range, 25-75 years) with fever of unknown origin or clinical signs and symptoms of lung infection were examined with breath-hold single-shot half-Fourier turbo spin-echo MR imaging. To reduce image blurring and increase MR signal in the lungs, the echo time was shortened with generalized autocalibrating partially parallel acquisition (GRAPPA). Patients underwent thoracic CT (four detector rows and 1-mm section thickness [4 x 1 mm]; pitch, 6) as reference standard. Pulmonary abnormalities (ill-defined nodules, ground-glass opacity areas, and consolidation), their location and distribution, and lesion characteristics were analyzed at MR imaging by three readers, blinded to results of CT, in consensus. Frequencies were calculated for each feature; paired Wilcoxon rank sum test was used to examine whether differences between CT and MR imaging features were statistically significant (alpha < .05). Bonferroni adjustments were performed. Overall sensitivity, specificity, and positive and negative predictive values were determined., Results: Twenty-two patients had pulmonary abnormalities at CT. In 21 (95%) patients, pneumonia was correctly diagnosed with MR imaging. One false-negative finding occurred in a patient with ill-defined nodules smaller than 1 cm at CT. One false-positive finding with MR imaging was the result of blurring and respiratory artifacts (sensitivity, 95%; specificity, 88%; positive predictive value, 95%; negative predictive value, 88%). There was no significant difference in lesion location and distribution., Conclusion: With parallel imaging (GRAPPA technique) and fast MR imaging, detection of pulmonary abnormalities is almost as good as with CT. MR imaging has a slight disadvantage in its lower capability to assist in characterization of specific internal features, such as cavitations., ((c) RSNA, 2006.)

In recent years CT has been established as the method of choice for the diagnosis of central pulmonary embolism (PE) to the level of the segmental arteries. The key advantage of CT over competing modalities is the reliable detection of relevant alternative or additional disease causing the patient's symptoms. Although the clinical relevance of isolated peripheral emboli remains unclear, the alleged poor sensitivity of CT for the detection of such small clots has to date prevented the acceptance of CT as the gold standard for diagnosing PE. With the advent of multislice CT we can now cover the entire chest of a patient with 1-mm slices within one breath-hold. In comparison with thicker sections, the detection rate of subsegmental emboli can be significantly increased with 1-mm slices. In addition, the interobserver correlation which can be achieved with 1-mm sections by far exceeds the reproducibility of competing modalities. Meanwhile use of multislice CT for a combined diagnosis of PE and deep venous thrombosis with the same modality appears to be clinically accepted. In the vast majority of patients who receive a combined thoracic and venous multislice CT examination the scan either confirms the suspected diagnosis or reveals relevant alternative or additional disease. The therapeutic regimen is usually chosen based on the functional effect of embolic vascular occlusion. With the advent of fast CT scanning techniques, also functional parameters of lung perfusion can be non-invasively assessed by CT imaging. These advantages let multislice CT appear as an attractive modality for a non-invasive, fast, accurate, and comprehensive diagnosis of PE, its causes, effects, and differential diagnoses.