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.

Data Logging Evidence of Cochlear Implant Use in Single-Sided and Bilateral Deafness.

PURPOSE: This study analyses data logs in order to investigate the usage pattern of cochlear implant (CI) recipients with single-sided deafness (SSD-CI) and bilaterally deaf, uni- or bilaterally implanted CI recipients (Uni-CI and Bil-CI). Data logging is available from SCAN, an automated auditory scene classifier which categorizes auditory input into 6 listening environments. METHODS: CI usage data were retrospectively available from data logs of 206 CI recipients using the Nucleus 6 system obtained between January 2013 and June 2015. For all recipients, we analysed time on air and time spent in the listening environments. For statistical analysis, we matched the CI recipients according to age and duration of CI experience and classified them into 4 age groups. RESULTS: SSD-CI showed a similar time on air compared to Uni- and Bil-CI. Usage behaviour of SSD-CI was comparable to Uni- and Bil-CI regarding exposure to music, speech in quiet and speech in noise. With increasing age, exposure to quiet increased and exposure to music decreased across all CI recipient groups in relation to time on air. CONCLUSION: In total, the CI usage pattern of SSD-CI is comparable for the majority of listening environments and age groups to that of Uni- and Bil-CI. The results of our study show that SSD-CI benefit equally from CI implantation.

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.

High-dose chemotherapy with autologous haematopoietic stem cell support for relapsed or refractory primary CNS lymphoma: a prospective multicentre trial by the German Cooperative PCNSL study group.

To investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL), we conducted a single-arm multicentre study for immunocompetent patients (<66 years) with PCNSL failing high-dose methotrexate)-based chemotherapy. Induction consisted of two courses of rituximab (375 mg/m2), high-dose cytarabine (2 × 3 g/m2) and thiotepa (40 mg/m2) with collection of stem cells in between. Conditioning for HCT-ASCT consisted of rituximab 375 mg/m2, carmustine 400 mg/m2 and thiotepa (4 × 5 mg/kg). Patients commenced HCT-ASCT irrespective of response after induction. Patients not achieving complete remission (CR) after HCT-ASCT received whole-brain radiotherapy. Primary end point was CR after HCT-ASCT. We enrolled 39 patients; median age and Karnofsky performance score are 57 years and 90%, respectively. About 28 patients had relapsed and 8 refractory disease. About 22 patients responded to induction and 32 patients commenced HCT-ASCT. About 22 patients (56.4%) achieved CR after HCT-ASCT. Respective 2-year progression-free survival (PFS) and overall survival (OS) rates were 46.0% (median PFS 12.4 months) and 56.4%; median OS not reached. We recorded four treatment-related deaths. Thiotepa-based HCT-ASCT is an effective treatment option in eligible patients with r/r PCNSL. Comparative studies are needed to further scrutinise the role of HCT-ASCT in the salvage setting.

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study).

To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 days 2, 16, 30), procarbazine (60 mg/m2 days 2-11) and lomustine (110 mg/m2, day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.

Independence and health related quality of life in 200 onco-geriatric surgical patients within 6 months of follow-up: Who is at risk to lose?

AIMS: Comprehensive Geriatric Assessment (CGA) provides information on aspects of older patients to predict risks and benefits of interventions. METHODS: To evaluate the application of CGA (including quality of life (QOL)) for the risk prediction of postoperative dependence and QOL in elderly patients with malignant tumours, a prospective observational study including 200 patients >70 years was performed. The primary outcome was postoperative activities of daily living (ADL < 95), secondary outcome was QOL at 6 months. Multivariate regression was performed to assess the impact of associated factors (socio-demographic, clinical, functional, cognitive variables, resilience, and EORTC-QLQ-C30 QOL). RESULTS: Median age of patients was 75 (70-88) years with 69% males. The majority of operations was for colon carcinoma; morbidity was 24.8%, mortality 1.5%. Impairment in ADL (<95) affected 6.7% (13/195) pre-, and 9.7% (12/124) post-operatively. Analyzing factors predicting loss of ADL, the following reached significance: BMI (OR: 1.7; p = 0.019), ADL (OR: 0.67; p = 0.0317), and of the QLQ-C30: diarrhea (OR: 1.04; p = 0.013), emotional functioning (OR: 0.91; p = 0.0242), physical functioning (OR: 0.92; p = 0.027). QOL paralleled ADL (pre-op: 65.4 to 67 postoperatively, respectively); predictive were: Karnofsky Index (Parameter Estimate (PE): 0.55; p = 0.0003) and (QLQ-C30) emotional functioning (PE: 0.14; p = 0.0208). CONCLUSIONS: Those considered for oncologic surgery can be assured that few lose independence. CGA/QOL highlight signs of vulnerability and options for pre-habilitation. Registries including a minimal CGA data set will make pre-selections reproducible and objectify risk/benefit estimations - relevant for those withheld from potentially curative surgery.

High Rates of Thromboembolic Events in Patients with Germ Cell Cancer Undergoing Cisplatin-Based Polychemotherapy.

BACKGROUND: We examined whether or not extended prophylaxis with low molecular weight heparin (LMWH) would significantly reduce thromboembolic event (TEE) rates in germ cell cancer patients undergoing cisplatin-based chemotherapy. PATIENTS AND METHODS: LMWH prophylaxis was given from the first day of chemotherapy until 21 days after completing the last chemotherapy cycle to 45 out of 93 (48.4%) patients (extended), and to 48 out of 93 (51.6%) patients during their hospitalization only (limited) between January 2008 and December 2013. Patients were analyzed retrospectively for TEEs such as deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) or peripheral arterial thrombosis. RESULTS: A total of 22/93 (23.7%) patients experienced 30 TEE during chemotherapy: 12 out of 30 (40%) deep vein thrombosis, 4 out of 30 (13.3%) MI, 10 out of 30 (33.3%) PE and 4 out of 30 peripheral arterial thrombosis (13.3%). TEE rates in both groups did not differ significantly (extended: 26.7 vs. limited: 20.8%). CONCLUSIONS: The introduction of extended LMWH prophylaxis did not significantly reduce TEE rates in our patient cohort.

Endovascular Cooling Catheter for Selective Brain Hypothermia: An Animal Feasibility Study of Cooling Performance.

BACKGROUND AND PURPOSE: Therapeutic hypothermia represents a promising neuroprotective treatment in acute ischemic stroke. Selective cerebral hypothermia applied early, prior to and during endovascular mechanical recanalization therapy, may be beneficial in the critical phase of reperfusion. We aimed to assess the feasibility of a new intracarotid cooling catheter in an animal model. MATERIALS AND METHODS: Nine adult sheep were included. Temperature probes were introduced into the frontal and temporal brain cortices bilaterally. The cooling catheter system was introduced into a common carotid artery. Selective blood cooling was applied for 180 minutes. Systemic and local brain temperatures were measured during cooling and rewarming. Common carotid artery diameters and flow were measured angiographically and by Doppler sonography. RESULTS: The common carotid artery diameter was between 6.7 and 7.3 mm. Common carotid artery blood flow velocities increased moderately during cooling and after catheter removal. Maximum cerebral cooling in the ipsilateral temporal cortex was -4.7°C (95% CI, -5.1 to -4.0°C). Ipsilateral brain temperatures dropped significantly faster and became lower compared with the contralateral cortex with maximum temperature difference of -1.3°C (95% CI, -1.5 to -1.0°C; P < .0001) and compared with systemic temperature (-1.4°C; 95% CI, -1.7 to -1.0°C; P < .0001). CONCLUSIONS: Sheep proved a feasible animal model for the intracarotid cooling catheter. Fast induction of selective mild hypothermia was achieved within the cooled cerebral hemisphere, with stable temperature gradients in the contralateral brain and systemic blood. Further studies are required to demonstrate any therapeutic benefit of selective cerebral cooling in a stroke model.

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.

Trained clinical nurse specialists proficiently obtain bone marrow aspirates and trephine biopsies in a nearly painless procedure--a prospective evaluation study.

Patients often experience bone marrow examinations (BMEs) as frightening and painful. Varying operators and uncertainty about who will perform the BME worsen their anxiety. In our study, clinical nurse specialists (CNSs) were trained to perform BMEs to ensure continuity and to test the feasibility, patient satisfaction, and biopsy quality. This exploratory evaluation assessed 574 BMEs at our tertiary center between January 2012 and February 2013, 398 BMEs performed by CNS and 176 by physicians. Our aims were to determine whether BMEs by CNS yield results similar to those of physicians, analyzing (1) patient satisfaction with the BME (a) consent and (b) performance, (2) induced pain, and (3) quality of aspirates and length of trephine biopsies. When performed by CNS, 100 % of the patients were satisfied with the consent procedure and 99 % with the BME performance (physicians 99 and 91 %, respectively). The median pain score was low when both CNS and physicians performed the BME, with no or only mild pain in 92 and 76 % of patients, respectively. Bone marrow (BM) aspirates by CNS and physicians were assessed as technically evaluable in ~70 %; moreover, the median length of trephine biopsies was similar when performed by CNS or physicians with 12 and 13 mm, respectively. In conclusion, BMEs conducted by motivated CNS and within a structured training program are feasible and yield equal outcomes compared to physicians. The use of adequate pain management during BMEs by trained and experienced operators results in an extremely rare use of sedatives, low pain scores, and high patient satisfaction.

MR angiography at 3 Tesla to assess proximal internal carotid artery stenoses: contrast-enhanced or 3D time-of-flight MR angiography?

PURPOSE: The aim of this study was to compare the diagnostic accuracy of 3D time-of-flight (TOF-MRA) and contrast-enhanced (CE-MRA) magnetic resonance angiography at 3 T for detection and quantification of proximal high-grade stenosis using multidetector computed tomography angiography (MDCTA) as reference standard. METHODS: The institutional ethics committee approved this prospective study. A total of 41 patients suspected of having internal carotid artery (ICA) stenosis underwent both MDCTA and MRA. CE-MRA and TOF-MRA were performed using a 3.0-T imager with a dedicated eight-element cervical coil. ICA stenoses were measured according to the North American Symptomatic Carotid Endarterectomy Trial criteria and categorized as 0-25 % (minimal), 25-50 % (mild), 50-69 % (moderate), 70-99 % (high grade), and 100 % (occlusion). Sensitivity and specificity for the detection of high-grade ICA stenoses (70-99 %) and ICA occlusions were determined. In addition, intermodality agreement was assessed with κ-statistics for detection of high-grade ICA stenoses (70-99 %) and ICA occlusions. RESULTS: A total of 80 carotid arteries of 41 patients were reviewed. Two previously stented ICAs were excluded from analysis. On MDCTA, 7 ICAs were occluded, 12 ICAs presented with and 63 without a high-grade ICA stenosis (70-99 %). For detecting 70-99 % stenosis, both 3D TOF-MRA and CE-MRA were 91.7 % sensitive and 98.5 % specific, respectively. Both MRA techniques were highly sensitive (100 %), and specific (CE-MRA, 100 %; TOF-MRA, 98.7 %) for the detection of ICA occlusion. However, TOF-MRA misclassified one high-grade stenosis as occlusion. Intermodality agreement for detection of 70-99 % ICA stenoses was excellent between TOF-MRA and CE-MRA [κ = 0.902, 95 % confidence interval (CI) = 0.769-1.000], TOF-MRA and MDCTA (κ = 0.902, 95 % CI = 0.769-1.000), and CE-MRA and MDCTA (κ = 0.902, 95 % CI = 0.769-1.000). CONCLUSION: Both 3D TOF-MRA and CE-MRA at 3 T are reliable tools for detecting high-grade proximal ICA stenoses (70-99 %). 3D TOF-MRA might misclassify pseudo-occlusions as complete occlusions. If there are no contraindications for CE-MRA, CE-MRA is recommended as primary MR imaging modality.

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.

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.

Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2 overexpressing metastatic pancreatic cancer.

BACKGROUND: New therapeutic options for metastatic pancreatic cancer are urgently needed. In pancreatic cancer, overexpression of the epidermal growth factor receptor 2 (HER2) has been reported in up to 45%. This multicentre phase II study investigated the efficacy and toxicity of the HER2 antibody trastuzumab combined with capecitabine in the patients with pancreatic cancer and HER2 overexpression. METHODS: Primary endpoint was progression-free survival (PFS) after 12 weeks. A total of 212 patients were screened for HER2 expression. RESULTS: Immunohistochemical (IHC) HER2 expression was: 83 (40%) grade 0, 71 (34%) grade 1, 31 (15%) grade 2, 22 (11%) grade 3. A total of 17 patients with IHC +3 HER2 expression or gene amplification could be assessed for the treatment response. Grade 3/4 treatment toxicities were: each 7% leucopenia, diarrhoea, nausea and hand-foot syndrome. Progression-free survival after 12 weeks was 23.5%, median overall survival (OS) 6.9 months. CONCLUSION: This study demonstrates +3 HER2 expression or gene amplification in 11% of patients. Contrary to breast and gastric cancer, only 7 out of 11 (64%) patients with IHC +3 HER2 expression showed gene amplification. Although the therapy was well tolerated, PFS and OS did not perform favourably compared with standard chemotherapy. Together, we do not recommend further evaluation of anti-HER2 treatment in patients with metastatic pancreatic cancer.

Induction of graft versus malignancy effect after unrelated allogeneic PBSCT using donor lymphocyte infusions derived from frozen aliquots of the original graft.

To evaluate safety and efficacy of donor lymphocyte infusions (DLI), derived from frozen aliquots of the original G-CSF-stimulated graft after allogeneic PBSCT from unrelated donors, data of 121 patients with hematological malignancies treated with DLIs were retrospectively analyzed. Indications for PBSCT were AML/myelodysplastic syndrome (n=63/8), ALL (n=17), lymphoma (n=13), multiple myeloma (n=10) and myeloproliferative syndrome (n=10). Reasons for DLI were hematological relapse (n=81), molecular and/or cytogenetic relapse (n=5), mixed chimerism (n=22) and prophylactic DLI in high-risk patients (n=13). DLIs were well tolerated with no acute adverse reactions. DLI-induced acute-type GvHD (aGvHD) was observed in 19 patients and chronic-type GvHD (cGvHD) developed in 14 patients. Three patients died of GvHD complications. DLI induced CR, complete chimerism or PR in 34 patients; 24 patients had stable disease, 50 patients progressed and 13 patients were not evaluable for response. Objective response was more obvious for molecular relapse (5/5) or mixed chimerism (14/22) compared with hematological relapse (13/81). Median survival after first DLI was 10.4 months (95% confidence interval: 4.4-26.0). Cryopreserved G-CSF-stimulated DLI, derived from allogeneic grafts are safe and immunoreactive, and can be applied early in case of mixed chimerism and molecular or cytogenetic relapse.

Criteria for the differential indication of asthma education versus asthma instruction for families of preschoolers: results from the randomized DIAT2 study (Differential Indication of Asthma Trainings in Toddlers).

BACKGROUND: Asthma management of preschoolers is more improved by a family oriented psycho-educational program provided by a multi-professional team than by a short instruction alone. For some families however an instruction could be sufficient. Criteria to assign education or instruction to asthmatic schoolchildren (DIA) have been evaluated . This paper describes the use of those criteria in the Preschoolers' and parents' asthma education trial (P (2)AET) . PATIENTS: DIA at study entry were available of 233 children (aged 2-5 [mean 3.9] years) participating in the randomised controlled P (2)AET (education, instruction, waiting group). Children had been included after having at least 3 obstructive episodes in their life plus chronic or recurrent wheeze in the 6 months before the start of the study. 74 % were on inhaled corticosteroids. METHODS: Logistic regression procedures were used to assess the predictive value of DIA and possible confounders on the success of the interventions (education and instruction). RESULTS: Regarding the outcome "better in asthma management test" education is superior to instruction (OR 5.2; CI 1.7-16). DIA "quarrel about inhalation" indicates an even greater advantage of education (OR 19; CI 2-176). An equal high advantage was found, when there was NO "need for peer support" (OR 11; CI 2-64). CONCLUSION: Families with asthmatic preschoolers displaying dysfunctional interaction, which can only be corrected in an educational process, should be provided with the psycho-educational program promptly.

Bioavailability of vitamin D2 from UV-B-irradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D: a randomized controlled trial.

BACKGROUND/OBJECTIVES: Mushrooms contain very little or any vitamin D(2) but are abundant in ergosterol, which can be converted into vitamin D(2) by ultraviolet (UV) irradiation. Our objective was to investigate the bioavailability of vitamin D(2) from vitamin D(2)-enhanced mushrooms by UV-B in humans, and comparing it with a vitamin D(2) supplement. SUBJECTS/METHODS: Fresh mushrooms were irradiated with an UV-B dose of 1.5 J/cm(2), increasing vitamin D(2) content from <1 to 491 µg/100 g and made to an experimental soup. In this 5-week, single-blinded, randomized, placebo-controlled trial, 26 young subjects with serum 25-hydroxyvitamin D (25OHD) ≤ 50 nmol/l were randomly assigned into three groups ((a) mushroom, (b) supplement and (c) placebo). They received during winter (a) 28,000 IU (700 µg) vitamin D(2) via the experimental soup, or (b) 28,000 IU vitamin D(2) via a supplement or (c) placebo, respectively. RESULTS: After 2 weeks, serum 25OHD was significantly higher in the mushroom than in the placebo group (P=0.001). The serum 25OHD concentrations in the mushroom and supplement groups rose significantly and similarly over the study period by 3.9 nmol/l (95% confidence interval (95% CI): 2.9, 4.8) and by 4.7 nmol/l per week (95% CI: 3.8, 5.7), respectively. CONCLUSIONS: We are the first to demonstrate in humans that the bioavailability of vitamin D(2) from vitamin D(2)-enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin D(2) supplement. This trial was registered at http://germanctr.de as DRKS00000195.

[Unilateral deafness and cochlear implantation: audiological diagnostic evaluation and outcomes]. / Einseitige Taubheit und Cochlear-implant-Versorgung: Audiologische Diagnostik und Ergebnisse.

Cochlear implantation (CI) is a new form of treatment in the rehabilitation of single-sided deafness. The patient requires thorough initial examination and a full explanation of alternative treatment options prior to determining the indication for CI treatment. To date, we have treated 28 patients with CI, of whom data are available for 11 after 12 months. We examined speech comprehension in background noise and localisation ability 12 months after CI implantation compared to conventional CROS (contralateral routing of signal) hearing aids, BAHA (bone-anchored hearing aid) and hearing in untreated patients. In addition, we determined the subjective handicap (HHIE, hearing handicap inventory for the elderly) and the subjective success (IOI-HA, international outcome inventory for hearing aids; SSQ, spatial and qualities of hearing scale) of each treatment option. After 12 months' experience, the results show a significantly better localisation ability and an improvement in speech comprehension in background noise with CI than with the other treatment options. Subjective results also show a clear benefit with CI. Careful patient selection is a decisive factor for successful treatment of this patient group. Under these conditions, CI is a treatment option with which significant improvement in speech comprehension and localization ability in single-sided deafness is possible.