Sequential low-dose CT thorax scans to determine invasive pulmonary fungal infection incidence after allogeneic hematopoietic cell transplantation.

Invasive fungal disease (IFD) during neutropenia goes along with a high mortality for patients after allogeneic hematopoietic cell transplantation (alloHCT). Low-dose computed tomography (CT) thorax shows good sensitivity for the diagnosis of IFD with low radiation exposure. The aim of our study was to evaluate sequential CT thorax scans at two time points as a new reliable method to detect IFD during neutropenia after alloHCT. We performed a retrospective single-center observational study in 265/354 screened patients admitted for alloHCT from June 2015 to August 2019. All were examined by a low-dose CT thorax scan at admission (CT t0) and after stable neutrophil recovery (CT t1) to determine the incidences of IFD. Furthermore, antifungal prophylaxis medications were recorded and cohorts were analyzed for statistical differences in IFD incidence using the sequential CT scans. In addition, IFD cases were classified according to EORTC 2008. At CT t0 in 9.6% of the patients, an IFD was detected and antifungal therapy initiated. The cumulative incidence of IFD in CT t1 in our department was 14%. The use of Aspergillus-effective prophylaxis through voriconazole or posaconazole decreased CT thorax t1 suggesting IFD is statistically significant compared to prophylaxis with fluconazole (5.6% asp-azol group vs 16.3% fluconazole group, p = 0.048). In 86%, CT t1 was negative for IFD. Low-dose sequential CT thorax scans are a valuable tool to detect pulmonary IFDs and guide antifungal prophylaxis and therapies. Furthermore, a negative CT t1 scan shows a benefit by allowing discontinuation of antifungal medication sparing patients from drug interactions and side effects.

Prognostic factors for survival after allogeneic transplantation in acute lymphoblastic leukemia.

Allogeneic stem cell transplantation (allo-SCT) offers a curative option in adult patients with acute lymphoblastic leukemia (ALL). Prognostic factors for survival after allo-SCT have not been sufficiently defined: pheno-/genotype, patients´ age, conditioning regimens and remission at allo-SCT are under discussion. We analyzed the outcome of 180 consecutive adult ALL-patients undergoing allo-SCT at our center between 1995 and 2018 to identify specific prognostic factors. In our cohort 19% were older than 55 years, 28% had Philadelphia-positive B-ALL, 24% T-ALL. 54% were transplanted in first complete remission (CR1), 13% in CR2 after salvage therapy, 31% reached no remission (8% within first-line, 23% within salvage therapy). In 66% conditioning contained total body irradiation (TBI). With a median follow-up of 10 years, we observed an overall survival of 33% at 10 years, and a progression free survival of 31%. The cumulative incidence of relapse was 41% at 10 years, the cumulative incidence of non-relapse mortality 28%. Acute graft-versus-host disease (GvHD) II°-IV° occurred in 31%, moderate/severe chronic GvHD in 27%. Survival was better in patients reaching CR before allo-SCT and in those receiving TBI. No difference between patients younger/older than 55 years and between different phenotypes was observed. Survival after allo-SCT improved considerably over the last decades.

It's never too late - balance and endurance training improves functional performance, quality of life, and alleviates neuropathic symptoms in cancer survivors suffering from chemotherapy-induced peripheral neuropathy: results of a randomized controlled trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) can affect functional performance and quality of life considerably. Since balance training has proven to enhance physical function, it might be a promising strategy to manage CIPN-induced functional impairments. METHODS: Fifty cancer survivors with persisting CIPN after finishing their treatment were randomly allocated to an intervention (IG) or active control group (CG). The IG did endurance plus balance training, the CG only endurance training (twice weekly over 12 weeks). Pre- and post-assessments included functional performance, cardiorespiratory fitness, vibration sense, and self-reported CIPN symptoms (EORTC QLQ-CIPN20). RESULTS: Intention-to-treat analyses (n = 41) did not reveal a significant group difference (CG minus IG) for sway path in semi-tandem stance after intervention (primary endpoint), adjusted for baseline. However, our per-protocol analysis of 37 patients with training compliance ≥70% revealed: the IG reduced their sway path during semi-tandem stance (- 76 mm, 95% CI -141 - -17; CG: -6 mm, 95% CI -52 - 50), improved the duration standing on one leg on instable surface (11 s, 95% CI 8-17; CG: 0 s, 95%CI 0-5) and reported decreased motor symptoms (-8points, 95% CI -18 - 0; CG: -2points 95% CI -6 - 2). Both groups reported reduced overall- (IG: -10points, 95% CI -17 - -4; CG: -6points, 95% CI -11 - -1) and sensory symptoms (IG: -7points, 95% CI -15 - 0; CG: -7points, 95% CI -15 - 0), while only the CG exhibited objectively better vibration sense (knuckle: 0.8points, 95% CI 0.3-1.3; IG: 0.0points, 95% CI -1.1 - 0.9; patella: 1.0points, 95% CI 0.4-1.6: IG: -0.8points, 95% CI -0.2 - 0.0). Furthermore, maximum power output during cardiopulmonary exercise test increased in both groups (IG and CG: 0.1 W/kg, 95% CI 0.0-0.2), but only the CG improved their jump height (2 cm, 95% CI 0.5-3.5; IG: 1 cm, 95% CI -0.4 - 3.2). CONCLUSION: We suppose that endurance training induced a reduction in sensory symptoms in both groups, while balance training additionally improved patients' functional status. This additional functional effect might reflect the IG's superiority in the CIPN20 motor score. Both exercises provide a clear and relevant benefit for patients with CIPN. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) number: DRKS00005419 , prospectively registered on November 19, 2013.

ESPEN expert group recommendations for action against cancer-related malnutrition.

Patients with cancer are at particularly high risk for malnutrition because both the disease and its treatments threaten their nutritional status. Yet cancer-related nutritional risk is sometimes overlooked or under-treated by clinicians, patients, and their families. The European Society for Clinical Nutrition and Metabolism (ESPEN) recently published evidence-based guidelines for nutritional care in patients with cancer. In further support of these guidelines, an ESPEN oncology expert group met for a Cancer and Nutrition Workshop in Berlin on October 24 and 25, 2016. The group examined the causes and consequences of cancer-related malnutrition, reviewed treatment approaches currently available, and built the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice. The content of this position paper is based on presentations and discussions at the Berlin meeting. The expert group emphasized 3 key steps to update nutritional care for people with cancer: (1) screen all patients with cancer for nutritional risk early in the course of their care, regardless of body mass index and weight history; (2) expand nutrition-related assessment practices to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function; (3) use multimodal nutritional interventions with individualized plans, including care focused on increasing nutritional intake, lessening inflammation and hypermetabolic stress, and increasing physical activity.

Secular trends of bloodstream infections during neutropenia in 15 181 haematopoietic stem cell transplants: 13-year results from a European multicentre surveillance study (ONKO-KISS).

OBJECTIVES: Antibacterial resistance is emerging in patients undergoing haematopoietic stem cell transplantation (HSCT), and most data on the epidemiology of bloodstream infections (BSI)-causing pathogens come from retrospective single-centre studies. This study sought to investigate trends in the epidemiology of BSI in HSCT patients from a prospective multicentre cohort. METHODS: We investigated changes in the incidence of causative organisms of BSI during neutropenia among adult HSCT patients for 2002-2014. The data were collected from a prospective cohort for infection surveillance in 20 haematologic cancer centres in Germany, Austria and Switzerland (ONKO-KISS). RESULTS: A total of 2388 of 15 181 HSCT patients with neutropenia (1471 allogeneic (61.6%) and 917 autologous (38.4%) HSCT) developed BSI (incidence 15.8% per year). The incidence of Gram-negative BSI increased over time both in patients after allogeneic HSCT (allo-HSCT) and autologous HSCT (auto-HSCT). BSI caused by Escherichia coli in allo-HSCT patients increased from 1.1% in 2002 to 3.8% in 2014 (3/279 vs. 31/810 patients, p <0.001), and the incidence of BSI caused by enterococci increased from 1.8% to 3.3% (5 vs. 27 patients, p <0.001). In contrast, the incidence of BSI due to coagulase-negative staphylococci decreased in allo-HSCT patients from 8.2% to 5.1%, (23 vs. 40 patients, p <0.001) and in auto-HSCT patients from 7.7% to 2.0% (13/167 vs. 30/540 patients; p = 0.028 for period 2002-2011). No significant trends were observed for the incidence of BSI due to methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci or extended-spectrum ß-lactamase-producing Enterobacteriaceae. The BSI case fatality remained unchanged over the study period (total of 477 fatalities, 3.1%). CONCLUSIONS: The incidence of Gram-negative BSI significantly increased over time in this vulnerable patient population, providing evidence for reevaluating empiric therapy for neutropenic fever in HSCT patients.

ESPEN guidelines on nutrition in cancer patients

Cancers are among the leading causes of morbidity and mortality worldwide, and the number of new cases is expected to rise significantly over the next decades. At the same time, all types of cancer treatment, such as surgery, radiation therapy, and pharmacological therapies are improving in sophistication, precision and in the power to target specific characteristics of individual cancers. Thus, while many cancers may still not be cured they may be converted to chronic diseases. All of these treatments, however, are impeded or precluded by the frequent development of malnutrition and metabolic derangements in cancer patients, induced by the tumor or by its treatment. These evidence-based guidelines were developed to translate current best evidence and expert opinion into recommendations for multi-disciplinary teams responsible for identification, prevention, and treatment of reversible elements of malnutrition in adult cancer patients. The guidelines were commissioned and financially supported by ESPEN and by the European Partnership for Action Against Cancer (EPAAC), an EU level initiative. Members of the guideline group were selected by ESPEN to include a range of professions and fields of expertise. We searched for meta-analyses, systematic reviews and comparative studies based on clinical questions according to the PICO format. The evidence was evaluated and merged to develop clinical recommendations using the GRADE method. Due to the deficits in the available evidence, relevant still open questions were listed and should be addressed by future studies. Malnutrition and a loss of muscle mass are frequent in cancer patients and have a negative effect on clinical outcome. They may be driven by inadequate food intake, decreased physical activity and catabolic metabolic derangements. To screen for, prevent, assess in detail, monitor and treat malnutrition standard operating procedures, responsibilities and a quality control process should be established at each institution involved in treating cancer patients. All cancer patients should be screened regularly for the risk or the presence of malnutrition. In all patients - with the exception of end of life care - energy and substrate requirements should be met by offering in a step-wise manner nutritional interventions from counseling to parenteral nutrition. However, benefits and risks of nutritional interventions have to be balanced with special consideration in patients with advanced disease. Nutritional care should always be accompanied by exercise training. To counter malnutrition in patients with advanced cancer there are few pharmacological agents and pharmaconutrients with only limited effects. Cancer survivors should engage in regular physical activity and adopt a prudent diet.

Long-term follow-up of therapy-related myelodysplasia and AML patients treated with allogeneic hematopoietic cell transplantation.

The outcome of patients with therapy-related myelodysplasia (t-MDS) or t-AML is very poor. The only curative treatment option implements allogeneic hematopoietic cell transplantation (aHCT); however, long-term follow-up data beyond 5 years are scarce. Here we report on a cohort of 79 consecutive patients with a median age of 58 years (range (r): 20-76) at transplantation and a median follow-up of 7.5 years (r: 0.07-19.0). Only 19 (24.1%) patients were in CR before aHCT. Non-relapse mortality and relapse rates were 23% (95% confidence interval, 15-35%) and 42% (32-55%) at 5 years, and 32% (22-46%) and 44% (34-57%) at 10 years, respectively. Disease-free survival (DFS) and overall survival (OS) rates were 35% (24-46%) and 38% (27-49%) at 5 years, and 24% (14-36%) and 24% (13-36%) at 10 years, respectively. Although cytogenetic aberrations were associated with shorter DFS and higher relapse risk, persistent disease at the time of transplantation, an unrelated donor and patient age were not associated with shorter OS. In conclusion, long-term survival beyond 10 years of t-MDS/t-AML patients after aHCT is possible, even for refractory patients. Therefore, early donor search and rapid transplantation are warranted, also to decrease the risk of disease-related deterioration of patients' performance status.

Cerebrospinal fluid chimerism analysis in patients with neurological symptoms after allogeneic cell transplantation.

Central nervous system (CNS) complications have been described in patients undergoing allogeneic hematopoietic cell transplantation (alloHCT). Cerebrospinal fluid (CSF) analysis is included in the diagnostic workup in patients with neurological symptoms after alloHCT. CSF donor-recipient chimerism analysis usually is not used to evaluate patients with neurological complications after alloHCT. To assess the potential contribution of CSF donor-recipient chimerism in patients with neurological complications, we analyzed 85 CSF samples from 50 patients with neurological complications after alloHCT. After alloHCT, 21 patients showed the presence of recipient-derived DNA. In 13 of these patients, recurrence of the underlying disease was detected in CSF. There was a moderate correlation between the recipient DNA percentage as detected by short tandem repeat (STR) amplification and the cell concentration in CSF (Spearmann r: 0.66 P=0.004). The percentage of cells with immunophenotypic abnormalities from patients relapsing in the CNS detected by flow cytometry showed a strong correlation with the percentage of recipient-derived DNA in CSF assessed by STR analysis (Spearmann r: 0.83 P=0.0008). Donor-recipient chimerism analysis in CSF in patients with neurological symptoms after alloHCT is a practical, feasible and useful complementary method to the already established methodologies included in the diagnostic workup.

Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey.

Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.

5-Azacytidine and DLI can induce long-term remissions in AML patients relapsed after allograft.

UNLABELLED: DNA-hypomethylating agents are a viable treatment option for AML/myelodysplastic syndrome (MDS) relapse after allograft by upregulating Ags on blasts before DLI. Seventy-two patients with relapsed AML (n=62), MDS (n=8) and other myeloid neoplasms (n=2) after allograft were treated with low-dose 5-azacytidine and, if feasible, DLI. PATIENT CHARACTERISTICS: median age 62 years (range 20-75), 42% with adverse cytogenetics, 82% not in remission at transplant and 83% received fludarabine-based reduced-toxicity conditioning. Median duration from transplant to 5-azacytidine was 289 days (range 59-2133). Response criteria: CR, temporary disease control or treatment failure. A median of 2.7 courses (range 1-10) were administered; 65 out of 72 patients also received DLI (41 already before 5-azacytidine). Ten patients developed acute GVHD and two succumbed to treatment-related sepsis. CR rate was 9.7% (in two patients lasting >5 years), 44% had temporary disease control (median duration 71 days, range 31-380). Median survival from 5-azacytidine was 108 days, 21 patients proceeded to subsequent transplant. In multivariate analysis, peripheral blood blasts <1% were predictive of longer OS (P=0.03). Taken together, long-term remissions can be induced by this well-tolerated outpatient treatment, particularly in patients without peripheral blood blasts.

Clinical guidelines for gynecologic care after hematopoietic SCT. Report from the international consensus project on clinical practice in chronic GVHD.

Despite similarities relevant age- and gender-specific issues exist in the care of patients after allogeneic hematopoietic SCT (HSCT). Female genital chronic GVHD (cGVHD) has been markedly underreported in the past but has a significant impact on the patients' health and quality of life. Data on prevention and treatment of this complication are still limited. Here we present a comprehensive review summarizing the current knowledge, which was discussed during several meetings of the German, Austrian and Swiss Consensus Project on clinical practice in cGVHD. In this report, we provide recommendations for post-transplant gynecological care of cGVHD manifestations agreed upon by all participants. This includes guidelines for diagnosis, prevention, and therapeutic options and topical treatments in female patients with genital cGVHD and hormonal replacement treatment of premature ovarian failure for adult and pediatric patients and underlines the necessity for regular gynecological care and screening programs for women after HSCT.

Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy.

BACKGROUND: Lymphoma patients undergoing therapy must cope with the side-effects of the disease itself, therapy and associated immobility. Peripheral neuropathy (PNP), loss of balance control and weakness not only diminishes patients' quality of life (QOL), it can also affect planning and the dosage of therapy. Exercise may enable patients to reverse these declines, improving their performance level and QOL. PATIENTS AND METHODS: We carried out a randomized, controlled trial, assigning 61 lymphoma patients either to a control group (CG; N=31) or to a 36-week intervention (IG; N=30), consisting of sensorimotor-, endurance- and strength training twice a week. Primary end point was QOL; secondary end points included movement coordination, endurance, strength and therapy-induced side-effects. RESULTS: Intergroup comparison revealed improved QOL- (ΔT1-T0; P=0.03) and PNP-related deep sensitivity in the IG: 87.5% were able to reduce the symptom, compared with 0% in the CG (P<0.001). Significant differences in the change of balance control could be found between the groups, with the IG improving while the CG steadily declined (monopedal static ΔT3-T0; P=0.03; dynamic ΔT3-T0; P=0.007; perturbed mono-ΔT3-T0; P=0.009 and bipedal ΔT3-T0; P=0.006), failed attempts (monopedal static ΔT3-T0; P=0.02, dynamic ΔT3-T0; P<0.001and perturbed ΔT3-T0; P=0.006) and improved time to regain balance (ΔT3-T0; P=0.04). Moreover, the change in the aerobic performance level (ΔT3-T0; P=0.05) and additional amount of exercise carried out per week [metabolic equivalent (MET); P=0.02] differed significantly across groups. CONCLUSIONS: Exercise, especially sensorimotor training, is a feasible and promising method to support cancer patients during therapy. It improves patients QOL, reduces restrictions from side-effects such as PNP and improves patients' balance control, physical performance level and mobility. GERMAN CLINICAL TRIALS REGISTER NUMBER: DRKS00003894.

Improvement in the outcome of invasive fusariosis in the last decade.

Invasive fusariosis (IF) has been associated with a poor prognosis. Although recent series have reported improved outcomes, the definition of optimal treatments remains controversial. The objective of this study was to evaluate changes in the outcome of IF. We retrospectively analysed 233 cases of IF from 11 countries, comparing demographics, clinical findings, treatment and outcome in two periods: 1985-2000 (period 1) and 2001-2011 (period 2). Most patients (92%) had haematological disease. Primary treatment with deoxycholate amphotericin B was more frequent in period 1 (63% vs. 30%, p <0.001), whereas voriconazole (32% vs. 2%, p <0.001) and combination therapies (18% vs. 1%, p <0.001) were more frequent in period 2. The 90-day probabilities of survival in periods 1 and 2 were 22% and 43%, respectively (p <0.001). In period 2, the 90-day probabilities of survival were 60% with voriconazole, 53% with a lipid formulation of amphotericin B, and 28% with deoxycholate amphotericin B (p 0.04). Variables associated with poor prognosis (death 90 days after the diagnosis of fusariosis) by multivariable analysis were: receipt of corticosteroids (hazard ratio (HR) 2.11, 95% CI 1.18-3.76, p 0.01), neutropenia at end of treatment (HR 2.70, 95% CI 1.57-4.65, p <0.001), and receipt of deoxycholate amphotericin B (HR 1.83, 95% CI 1.06-3.16, p 0.03). Treatment practices have changed over the last decade, with an increased use of voriconazole and combination therapies. There has been a 21% increase in survival rate in the last decade.

Aspergillus PCR-based investigation of fresh tissue and effusion samples in patients with suspected invasive Aspergillosis enhances diagnostic capabilities.

Although it is a severe complication in immunocompromised patients, diagnosing invasive fungal disease (IFD), especially invasive aspergillosis (IA), remains difficult. In certain clinical scenarios, examining tissue samples for identification of the infectious organism becomes important. As culture-based methods rarely yield results, the performance of an Aspergillus-specific nested PCR in fresh tissue or pleural effusion samples was evaluated. Fresh tissue (n = 59) and effusion (n = 47) specimens from 79 immunocompromised patients were subjected to an Aspergillus-specific PCR assay. Twenty-six patients had proven (n = 20) or probable (n = 6) IFD, according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria, while the remaining patients were classified as having either possible IFD (n = 30) or no IFD (n = 23). IA was identified as the underlying IFD in 21/26 proven/probable cases. PCR positivity was observed for 18/21 proven/probable and 6 possible IA cases; cases classified as no IA did not show positive signals. Patients with proven IFD (n = 5) with cultures positive for non-Aspergillus molds also had negative Aspergillus PCR results. Aspergillus PCR performance analysis yielded sensitivity and specificity values of 86% (95% confidence interval [CI], 65% to 95%) and 100% (95% CI, 86% to 100%), respectively, thus leading to a diagnostic odds ratio of >200. In this analysis, good diagnostic performance of the PCR assay for detection of IA was observed for tissue samples, while effusion samples showed lower sensitivity rates. PCR testing represents a complementary tool; a positive PCR result strengthens the likelihood of IA, whereas IA seems unlikely in cases with negative results but findings could indicate non-Aspergillus IFD. Thus, PCR testing of these specimens enhances the diagnostic capabilities.

Comparison of a novel Aspergillus lateral-flow device and the Platelia® galactomannan assay for the diagnosis of invasive aspergillosis following haematopoietic stem cell transplantation.

PURPOSE: The detection of galactomannan in serum is a cornerstone for the diagnosis of invasive fungal disease (IFD). Because a delay in treatment initiation is associated with a poor outcome, the results have to be available promptly. However, due to methodological and economic reasons, the test frequencies of the commonly used galactomannan assays vary between daily to weekly, meaning that results may be available too late to be clinically useful. The novel Aspergillus lateral-flow device (Aspergillus-LFD) is a rapid test that may overcome these limitations. METHODS: We compared the diagnostic performance of the Aspergillus-LFD and the Platelia® Aspergillus EIA (GM-EIA) in serum from 101 patients during and after allogeneic haematopoietic stem cell transplantation (HSCT). Clinical data and sera were collected prospectively and patients classified according to the European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group (MSG) 2008 guidelines. RESULTS: By the end of hospitalisation, one proven, nine probable and 20 possible cases of IFD were identified. Depending on the number of positive serum samples required for test positivity, the sensitivities, specificities and diagnostic odds ratios in patients with proven and probable IFD were as follows. One positive serum required: Aspergillus-LFD 40.0 %, 86.8 % and 3.03; GM-EIA 40.0 %, 89.0 % and 3.64. Two positive sera required: Aspergillus-LFD 20.0 %, 97.8 % and 11.13; GM-EIA 30.0 %, 98.9 % and 38.57. Although the GM-EIA was positive in a higher percentage of samples, this did not result in an earlier diagnosis. CONCLUSIONS: If used as a screening test (one positive serum required for test positivity) or to rule out IFD, the Aspergillus-LFD has shown a comparable diagnostic performance to the GM-EIA. However, if the results have to be confirmed by a second positive serum, the GM-EIA exhibited superior sensitivity. In terms of practicability, the Aspergillus-LFD has demonstrated to be a quick (15 min) and easy-to-use test for single-patient detection of Aspergillus antigens.

Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML.

A second allograft was offered to 58 relapsed AML patients after conditioning with fludarabine 90-150 mg/m(2) and thiotepa 15 mg/kg, in most cases with active disease. Median age was 53 years (range 23-69), median time to relapse after the first allo-SCT was 326 (47-2189) days and median follow-up was 6.7 years. GVHD prophylaxis consisted mainly of CsA and alemtuzumab. Response rates at 1 month were CR in 50 and persistent disease in 3/53 evaluable patients. At 3 years, the relapse incidence (95% confidence interval) was 56 (45-71)%, the TRM 31 (21-46)%, the OS rate was 18 (9-29)% and the EFS rate was 13 (5-23)%. OS improved with younger patient age, longer relapse-free interval after the first allo-SCT and the development of chronic GVHD. Patients ≥ 65 years old who relapsed >12 months after the first allograft (n=20) had a 3-year OS rate of 41 (19-62)%. Conventional cytogenetics and FLT3 mutation status did not affect outcome. Our regimen is feasible and provides at least for a subgroup of patients with AML recurrence after allo-SCT a reasonable therapeutic option in an otherwise fatal situation. Further modifications and a better understanding of the underlying biology could help lower the risk of relapse.

Identification of risk factors for bronchiolitis obliterans syndrome after reduced toxicity conditioning before hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (allo-HCT) of older or patients with comorbidities has become possible due to new regimens for reduced-intensity conditioning. The use of fludarabine, carmustine and melphalan as the preparative regimen (FBM) reduces toxicity while providing substantial anti-leukemic activity. Chronic GVHD (cGVHD) of the lung or bronchiolitis obliterans syndrome (BOS) remains a serious non-infectious complication contributing to treatment-related morbidity. We conducted a retrospective analysis of 259 patients (median age: 61.5, range: 24-76 years) transplanted after FBM conditioning to identify and characterize clinical risk factors for developing BOS. The cumulative incidence rate of BOS was 4.2% (95% confidence interval (CI): 2.4-7.6%) at 1 year and 8.5% (95% CI: 5.6-12.9%) at 5 years after allo-HCT with a median follow-up of 36.5 (range: 3-136) months. In multivariate analysis, age <55 years at allo-HCT (who received 25% higher carmustin-dose in preparative regimen), pulmonary complications after allo-HCT and GVHD prophylaxis without in-vivo T-cell depletion (cyclosporine-A/ATG or cyclosporine-A/alemtuzumab) were associated with BOS. We observed no significant differences in clinical variables such as smoking or lung diseases before allo-HCT. In contrast to cGVHD affecting other organs, BOS showed no impact on overall survival. In conclusion, we identified risk factors associated with developing BOS after conditioning with a reduced toxicity protocol.