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Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

NOV-002 (a formulation of disodium glutathione disulfide) modulates signaling pathways involved in tumor cell proliferation and metastasis and enhances anti-tumor immune responsiveness in tumor models. The addition of NOV-002 to chemotherapy has been shown to increase anti-tumor efficacy in animal models and some early phase oncology trials. We evaluated the clinical effects of NOV-002 in primary breast cancer, whether adding NOV-002 to standard preoperative chemotherapy increased pathologic complete response rates (pCR) at surgery, and determined whether NOV-002 mitigated hematologic toxicities of chemotherapy and whether levels of myeloid derived suppressor cells (MDSC) were predictive of response. Forty-one women with newly diagnosed stages II-IIIc HER-2 negative breast cancer received doxorubicin-cyclophosphamide followed by docetaxel (AC → T) every 3 weeks and concurrent daily NOV-002 injections. The trial was powered to detect a doubling of pCR rate from 16 to 32% with NOV-002 plus AC → T (α = 0.05, β = 80%). Weekly complete blood counts were obtained as well as circulating MDSC levels on day 1 of each cycle were quantified. Of 39 patients with 40 evaluable tumors, 15 achieved a pCR (38%), meeting the primary endpoint of the trial. Concurrent NOV-002 resulted in pCR rates for AC → T chemotherapy higher than previously reported. Patients with lower levels of circulating MDSCs at baseline and on the last cycle of chemotherapy had significantly higher probability of a pCR ( P = 0.02). Further evaluation of NOV-002 in a randomized study is warranted. [ABSTRACT FROM AUTHOR]

Fifty-seven patients receiving unrelated donor (UD) BMT were matched for disease and stage with 57 recipients of genotypically matched related donor (MRD) BMT. All UD recipients were matched serologically for A and B and by high resolution for DR and DQ antigens. All patients received CsA and ‘short course’ methotrexate with folinic acid. Unrelated donor BMT patients also received thymoglobulin 4.5 mg/kg (6 mg/kg if <30 kg) in divided doses over 3 days pretransplant. For UD and RD BMT, respectively, incidence of acute GVHD grade II–IV was 19 ± 6% vs 36 ± 8%, grade III–IV 10 ± 6% vs 18 ± 7%, chronic GVHD 44 ± 8% vs 51 ± 8%, non-relapse mortality 15 ± 5% vs 8 ± 4% at 100 days, 28 ± 8% vs 36 ± 7% at 3 years. At 3 years, relapse was 45 ± 7% vs 42 ± 7%, and disease-free survival 39 ± 7% vs 37 ± 7%. None of these differences are significant. Three-year overall survival was identical at 42 ± 7%. For 29 patients with low/intermediate risk leukemia, disease-free survival was 68 ± 10% after UD BMT vs 59 ± 9% for RD BMT recipients (P = NS). Corresponding figures for high risk patients were 14 ± 7% and 21 ± 8%, respectively. We conclude that UD BMT recipients matched as above and given pretransplant ATG have similar outcomes to recipients of MRD BMT using conventional drug prophylaxis. Unrelated donor BMT should be considered in any circumstance where MRD BMT is routine.Bone Marrow Transplantation (2002) 30, 681–686. doi:10.1038/sj.bmt.1703674 [ABSTRACT FROM AUTHOR]

X-ray magnetic circular dichroism (X-MCD) was used as a large, element-specific and quantitative magnetic contrast mechanism in the soft X-ray microscopes at BESSY I (Berlin) and the ALS (Berkeley). The present state and potential of magnetic transmission X-ray microscopy (MTXM) is outlined. The possibility to record images in varying magnetic fields and the high spatial resolution down to 25 nm were used to image out-of-plane magnetized (4 ÅFe / 4 ÅGd)×75 systems. Magnetic domains could be studied in arrays of circular and square dots with lateral dimensions down to 180 nm. Hysteresis loops of individual dots were deduced using the direct proportionality of the X-MCD contrast to the sample magnetization. Images of a 3 nmCr / 50 nmFe / 6 nmCr film demonstrate for the first time that MTXM is also able to observe in-plane magnetized domains. In the future the possible applications of MTXM will be extended with regard to the strength of the external field, the available energy range and the sample conditions by building a dedicated transmission X-ray microscope for magnetic imaging at BESSY II. [ABSTRACT FROM AUTHOR]

Better predictive factors for autologous blood stem cell mobilization (BSCM) are needed. The purpose of this study was to determine if an independent association exists between lymphocyte or NK cell counts and BSCM. Data were analyzed on 141 consecutive patients aged 19–69 years (median 45) who received combined chemotherapy plus G-CSF for BSCM, and who had measurements of immune cells prior to BSCM. Of the 141 patients, 41% had breast cancer, 14% Hodgkin’s disease, 34% non-Hodgkin’s lymphoma, and 11% other diagnoses. BSCM involved dose-intensive cyclophosphamide, etoposide, cisplatin (DICEP) plus G-CSF 300 μg (<70 kg) or 480 μg (>70 kg) for 45% of patients, while the remaining 55% received other chemotherapy plus similar doses of G-CSF. Only a single apheresis was performed for 94% of patients. The following factors were analyzed for predictors of BSCM: age, gender, prior chemotherapy, prior radiotherapy, diagnosis, disease status, marrow involvement, mobilization regimen, Hb, WBC, platelet count, B cell, T cell, and NK cell counts. The peripheral blood CD34+ counts on the first day of apheresis (PBCD34) were 6–1783 × 106/l (median 150). The PBCD34 count correlated strongly with the number of CD34+ cells collected/l blood apheresed and with the number of CD34+ cells collected/kg. By multivariate analysis using continuous variables, relapsed status (P = 0.0003), not using DICEP mobilization (P = 0.0001), female gender (P = 0.0057), low platelet count (P = 0.051), and low CD3-16+56+ count (P = 0.0158) were associated with low PBCD34 counts. Using categorical variables, the only factors that independently predicted a PBCD34 count <150 × 106/l were: >1 prior chemotherapy regimen (odds ratio = 5.12, P = 0.0003), not using DICEP mobilization (odds ratio = 4.94, P = 0.0001), and CD3-16+56+ count <125... [ABSTRACT FROM AUTHOR]

This study determined the effects of high-dose chemotherapy (HDCT) with autologous blood stem cell transplantation (ASCT) on quality of life (QL) in women with metastatic breast cancer prior to, and during treatment, and up to 1-year post-ASCT. Thirty-three women diagnosed with metastatic breast cancer participated in a phase 1 clinical trial of a new combination of cyclophosphamide (CTX) and mitoxantrone (MXT), with dose escalation of paclitaxel. Longitudinal QL data were collected using the functional living index-cancer (FLIC) and symptom scales at seven time periods: pre-induction chemotherapy (CT), post-induction CT, post-high dose CT (HDCT), and at 3, 6, 9 and 12 months post-ASCT. FLIC scores indicated that the worst problems for patients were feelings of hardship on themselves and their families, followed by psychological functioning and physical functioning problems. The time around diagnosis of the metastatic disease and following HDCT were the worst times for all levels of quality of life, but anxiety and depression symptoms continued to increase in severity across the entire follow-up period. The symptoms that were most problematic were worry about the future, loss of sexual interest, anxiety about the treatment, general worrying, and joint pain. These data highlight the problems that women with metastatic breast cancer encounter at different stages of the disease and treatment process, and can be used to tailor psychosocial interventions appropriate for treating the relevant issues at different points in time. Bone Marrow Transplantation (2001) 27, 989–998. [ABSTRACT FROM AUTHOR]

The expression levels of a circulating extracellular domain of HER-2 can be detected in the plasma and serum of patients with metastatic breast cancer using an enzyme immunoassay (ELISA) method. In this study, we evaluated the clinical significance of high and low levels of HER-2 in the plasma of 46 patients with metastatic breast cancer enrolled in a clinical trial of high-dose chemotherapy (HDCT) using cyclophosphamide, mitoxantrone, and paclitaxel with autologous stem cell transplantation (ASCT). Using 2500 U/ml as the cut-point, 20 patients (46%) had elevated HER-2 levels (HER-2 positive). Our results suggest that patients with metastatic breast cancer and high soluble plasma HER-2 have a significantly poorer overall (OS) and progression-free survival (PFS) following high-dose chemotherapy with paclitaxel and ASCT. The median OS of patients with low levels of HER-2 was significantly longer (P < 0.01) than the median OS of patients with high levels of HER-2 (29.8 months vs 15.9 months). PFS was also significantly longer (P < 0.01) for patients who were HER-2-negative, than for patients who were HER-2-positive (13.0 vs 8.6 months). Univariate analysis showed that patients with liver or lung metastases had significantly reduced OS and PFS. Patients with metastases to two or more sites also had a significantly reduced time to disease progression, but not OS. In multivariable analysis, lung metastases contributed along with HER-2-positive status to determine a group of patients with significantly poorer OS. However, HER-2-positive status remained the only independent predictor of PFS. Bone Marrow Transplantation (2001) 27, 847–853. [ABSTRACT FROM AUTHOR]

Data from 170 consecutive patients aged 19–66 years (median age 46 years) who underwent unmanipulated autologous blood stem cell transplant (ASCT) were analyzed to determine if total CD34+ cells/kg infused, CD34+ subsets (CD34+41+, CD34+90+, CD34+33-, CD34+38-, CD34+38-DR-), peripheral blood CD34+ cell (PBCD34+) count on first apheresis day, or various clinical factors were associated with low blood counts 6 months post ASCT. Thirty-four patients were excluded from analysis either because of death (n = 17) or re-induction chemotherapy prior to 6 months post ASCT (n = 13), or because of lack of follow-up data (n = 4). Of the remaining 136 patients, 46% had low WBC (<4 × 109/l), 41% low platelets (<150 × 109/l), and 34% low hemoglobin (<120 g/l) at a median of 6 months following ASCT. By Spearman’s rank correlation, both the total CD34+ cell dose/kg and the PBCD34+ count correlated with 6 month blood counts better than any subset of CD34+ cells or any clinical factor. The PBCD34+ count was overall a stronger predictor of 6 month blood counts than was the total CD34+ cells/kg infused. Both factors retained their significance in multivariate analysis, controlling for clinical factors. In conclusion, subsets of CD34+ cells and clinical factors are inferior to the total CD34+ cell dose/kg and PBCD34+ count in predicting 6 month blood counts following ASCT. Bone Marrow Transplantation (2000) 26, 1299–1304. [ABSTRACT FROM AUTHOR]

We previously reported a 50% (95% CI = 33–76%) 5 year event-free survival (EFS) rate for 23 patients with Hodgkin’s disease (HD) who received salvage therapy with single agent high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT). Predictors of poor outcome included bulky disease and initial remission <1 year. since 1995, similar poor prognosis patients have been treated with double high-dose therapy consisting of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2(DICEP) for tumor cytoreduction and stem cell mobilization followed by HDM/ASCT. The purpose of the present study is to determine if the use of DICEP is associated with improved event-free (EFS) and overall survival (OAS) for patients treated with HDM/ASCT. From February 1981 to June 1999, 46 consecutive patients received HDM/ASCT for relapsed (n = 35) or refractory (n = 11) hd. dicep re-induction and blood stem cell mobilization was used for 21 patients. factors considered for univariate and multivariate analyses included age at transplant, number of failed chemotherapy regimens, prior radiotherapy, length of initial remission, relapsed or refractory disease status, extranodal relapse, b symptoms at relapse, bulk, post-asct radiotherapy, and dicep re-induction therapy. cox proportional hazards models were constructed for both event and death. dicep and hdm were well tolerated with no early treatment-related mortality or toxicity requiring life-sustaining measures. for all 46 patients, the projected 5 year efs was 52% (95% ci = 38–72%) and oas was 57% (95% ci = 40–82). factors independently associated with relapse in multivariate analysis included bulk >5 cm (RR = 6.38, P = 0.002), prior radiotherapy (RR = 3.59, P = 0.027), and not using DICEP (RR = 5.29, P = 0.005). factors independently associated with death included bulk >5 cm (RR = 5.13, P = 0.009), 3 prior chemotherapy regimens... [ABSTRACT FROM AUTHOR]

C-erbB-2/HER-2 (designated HER-2) is overexpressed in both primary and metastatic breast cancer and predicts poor prognosis. We investigated the expression of HER-2 in patients with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) with autologous blood stem cell (ABSC) support and correlated the presence (positive) or absence (negative) of HER-2 overexpression in these patients with response to treatment, progression-free survival (PFS) and overall survival (OS). The level of HER-2 expression was analyzed in 57 patients with metastatic breast cancer undergoing HDCT with ABSC support. Plasma from peripheral blood was taken at three different time points during the course of treatment and was analyzed using an enzyme immunoassay (EIA) to detect circulating levels of the extracellular portion of HER-2. HER-2 levels were elevated (>0.2 U/mg protein) in 27/57 (47.4%) patients at one or more time points during treatment. The level of HER-2 varied during the course of treatment. Following induction chemotherapy (ICT), five patients who were negative initially, showed overexpression of HER-2. Three patients overexpressed HER-2 only after HDCT/ABSC. Response to treatment was similar in patients independent of plasma HER-2 levels. Overexpression of HER-2 was associated with a significantly shorter PFS (P = 0.004, log rank) and OS (P = 0.003, log rank) after HDCT/ABSC. HER-2 overexpression, patient age, estrogen receptor status, progesterone receptor status, and previous hormone treatment were assessed by univariate and multivariate analysis. Univariate analysis determined that only HER-2 overexpression correlated significantly with decreases in progression free survival (P = 0.005, Cox regression). Decreased overall survival correlated significantly with HER-2 overexpression (P = 0.004) and decreased expression of both estrogen receptor (P = 0.032) and progesterone receptor (P = 0.039). In multivariate analysis of these variables, only HER-2 expression... [ABSTRACT FROM AUTHOR]

High-dose chemotherapy (HDCT) followed by autologous blood cell (ABC) transplantation has been used widely for patients with metastatic breast cancer (MBC). It has been shown by our group and others to be an effective means of achieving very high response rates including complete remission. Therefore, further reduction in toxicity and increased patient satisfaction is necessary. Fifty-three patients with MBC were enrolled in a feasibility study at our cancer centre with a three-step approach to outpatient observation after HDCT and ABC transplantation discharging our patients from hospital 6 days after reinfusion of ABC, 1 day after reinfusion of ABC and 1 day prior to reinfusion of ABC. The supportive care consisted of the use of 5-HT3 antagonists for nausea and vomiting, DMSO depletion, thorough body hygiene, prophylactic antibiotic, antifungal and virustatic drugs. In the event of febrile neutropenia, a standard evaluation and treatment was used. Only 22 patients were admitted for febrile neutropenia and two for haemorrhage. The median hospital stay was 2 days (range 1–7). The time to engraftment, need for transfusion and other toxicities were not different in patients who stayed entirely as outpatients. No toxic deaths occurred. In conclusion, HDCT followed by ABC transplantation can be safely administered to patients in the clinic with outpatient post-transplant observation. [ABSTRACT FROM AUTHOR]

During the last ten years we observed three non-hemophilic patients with factor(F) VIII: C inhibitors (2 women aged 68 and 80 and a man aged 51). In all three cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII: C level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrand's disease could be excluded. Therapy with F VIII: C concentrate, cryoprecipitate, or fresh-frozen plasma did not produce the expected increase in F VIII: C. Measurement of F VIII: C inhibitor levels (Bethesda Units, BU) revealed values in the range between 9 and 64 BU. The two patients subjected to long-term therapy with a combination of prednisone (initially 2-3 mg/kg BW) and azathioprine (2-3 mg/kg BW) responded positively; the F VIII: C concentration increased. The third patient, treated only with a low dose of prednisone (30 mg/day), did not show any reaction at all. Since hereditary hemophilia A could be excluded, the inhibitors apparently were acquired. Malignant tumors did not appear. In conclusion, long-term therapy of an acquired F VIII: C inhibitor with a combination of prednisone and azathioprine may lead to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency. [ABSTRACT FROM AUTHOR]

The evidence for use of high-dose chemotherapy and autologous stem cell transplantation for breast cancer still remains inconclusive at best. A number of prospective randomized phase III studies have been either published or presented recently or are underway in North America and Europe. It will be crucial to complete the available prospective randomized phase III study and obtain the data when all studies reach a mature status. Only then will level I evidence become available to determine the efficacy and effectiveness of high-dose chemotherapy and autologous stem cell transplantation in breast cancer. Bone Marrow Transplantation (2000) 25, 1017–1019. [ABSTRACT FROM AUTHOR]