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4.
Bone Marrow Transplant ; 56(4): 841-852, 2021 04.
Article in English | MEDLINE | ID: mdl-33130821

ABSTRACT

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.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Adult , Disease-Free Survival , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Retrospective Studies , Transplantation Conditioning , Transplantation, Homologous
5.
Ann Hematol ; 99(12): 2821-2829, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32734548

ABSTRACT

Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P < 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.


Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bendamustine Hydrochloride/administration & dosage , Lymphoma, Follicular/drug therapy , Rituximab/administration & dosage , Aged , Cohort Studies , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/mortality , Male , Middle Aged , Neoplasm Grading/methods , Prednisone/administration & dosage , Retrospective Studies , Survival Rate/trends , Treatment Outcome , Vincristine/administration & dosage
6.
Sens Actuators B Chem ; 122(2): 578-586, 2007 Mar 26.
Article in English | MEDLINE | ID: mdl-32288238

ABSTRACT

We describe herein a newly developed optical immunosensor for detection of antibodies directed against antigens of the Ebola virus strains Zaire and Sudan. We employed a photo immobilization methodology based on a photoactivatable electrogenerated poly(pyrrole-benzophenone) film deposited upon an indium tin oxide (ITO) modified conductive surface fiber-optic. It was then linked to a biological receptor, Ebola virus antigen in this case, on the fiber tip through a light driven reaction. The photochemically modified optical fibers were tested as an immunosensor for detection of antibodies against Ebola virus, in animal and human sera, by use of a coupled chemiluminescent reaction. The immunosensor was tested for sensitivity, specificity, and compared to standard chemiluminescent ELISA under the same conditions. The analyte, anti-Ebola IgG, was detected at a low titer of 1:960,000 and 1:1,000,000 for subtypes Zaire and Sudan, respectively. While the same serum tested by ELISA was one order (24 times) less sensitive.

7.
J Eur Acad Dermatol Venereol ; 33(6): 985-986, 2019 06.
Article in English | MEDLINE | ID: mdl-30983038
8.
Clin Radiol ; 73(5): 485-493, 2018 05.
Article in English | MEDLINE | ID: mdl-29246586

ABSTRACT

AIM: To evaluate the diagnostic per-lesion performance of a simulated gadoxetate disodium-enhanced abbreviated MRI (AMRI) in cirrhotic and chronic hepatitis B (CHB) patients for hepatocellular carcinoma (HCC) screening. MATERIALS AND METHODS: Seventy-nine consecutive patients at risk for HCC due to cirrhosis and/or CHB were included in this retrospective study. For each patient, the first gadoxetate disodium-enhanced MRI between 2008 through 2014 was analysed. Two independent readers read an anonymised abbreviated image set comprising axial T1-weighted (W) images with fat saturation in the hepatobiliary phase, 20 minutes or more after gadoxetate injection, and axial T2W single-shot fast spin echo images. Each observation >10 mm was scored as negative or suspicious for HCC. Inter-reader agreement was assessed. A composite reference standard was used to determine the per-lesion diagnostic performance for each reader. RESULTS: Inter-reader agreement was substantial (κ = 0.75). The final reference standard showed 27 HCCs in 13 patients (median 21 mm, range 11-100 mm). The two readers each correctly scored 23 as suspicious for HCC (sensitivity = 85.2%), scored a total of 27 and 32 observations as suspicious for HCC (positive predictive value [PPV] = 85.2% and 71.9%), and scored 83 and 78 observations or complete examinations as negative for HCC (negative predictive value [NPV] = 95.2% and 94.9%). CONCLUSIONS: The AMRI protocol provides higher per-lesion sensitivity and NPV than reported values for ultrasound, the current recommended technique for screening, and similar per-lesion sensitivity and PPV to reported values for complete dynamic contrast-enhanced MRI.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Contrast Media , Gadolinium DTPA , Liver Neoplasms/diagnostic imaging , Magnetic Resonance Imaging/methods , Carcinoma, Hepatocellular/etiology , Cross-Sectional Studies , Female , Humans , Liver Neoplasms/etiology , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity
9.
Oecologia ; 47(1): 141-144, 1980 Jan.
Article in English | MEDLINE | ID: mdl-28309643

ABSTRACT

Previous workers (McKenzie and Parsons, 1972, 1974; McKenzie, 1974; Briscoe et al., 1975) have found anomalous distributions of species of Drosophila, of sexes of D. melanogaster, and of Adh alleles in and around wineries in Australia and Spain. Field studies in California's Sonoma Valley provide evidence that the explanations advanced for these distributions may incorrect. The anomalous distribution of species was attributed to alcohol, either as a selective agent or as a behavioral stimulus. We find a virtually identical species distribution in the absence of environmental alcohol. The anomalous sex ratio was attributedd to differential survivall of the sexes when raised on alcohol. We present crude evidence thatehe difference may simply be a behavioral response to some product of fermentation, which need not be alcohol. Finally, the allele frequency difference reported from Spain was attributed to differential adult mortality on alcohol. We do not find an allele frequency difference even when alcohol is exposed, and therefore suggest that selection is occurring in pre-adult stages.

10.
Ann Oncol ; 27(11): 2111-2117, 2016 11.
Article in English | MEDLINE | ID: mdl-27742657

ABSTRACT

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) are rare sarcomas that can occur at any age. Surgical resection is the primary treatment for patients with localized disease; however, these tumors frequently recur. Less commonly, patients with IMTs develop or present with metastatic disease. There is no standard of care for these patients and traditional cytotoxic therapy is largely ineffective. Most IMTs are associated with oncogenic ALK, ROS1 or PDGFRß fusions and may benefit from targeted therapy. PATIENT AND METHODS: We sought to understand the genomic abnormalities of a patient who presented for management of metastatic IMT after progression of disease on crizotinib and a significant and durable partial response to the more potent ALK inhibitor ceritinib. RESULTS: The residual IMT was resected based on the recommendations of a multidisciplinary tumor sarcoma tumor board and analyzed by whole-genome mate pair sequencing. Analysis of the residual, resected tumor identified a chromoplectic TPM3-ALK rearrangement that involved many other known oncogenes and was confirmed by rtPCR. CONCLUSIONS: In our analysis of the treatment-resistant, residual IMT, we identified a complex pattern of genetic rearrangements consistent with chromoplexy. Although it is difficult to know for certain if these chromoplectic rearrangements preceded treatment, their presence suggests that chromoplexy has a role in the oncogenesis of IMTs. Furthermore, this patient's remarkable response suggests that ceritinib should be considered as an option after progression on crizotinib for patients with metastatic or unresectable IMT and ALK mutations.


Subject(s)
Neoplasm Recurrence, Local/drug therapy , Receptor Protein-Tyrosine Kinases/genetics , Sarcoma/drug therapy , Tropomyosin/genetics , Adult , Anaplastic Lymphoma Kinase , Crizotinib , Drug Resistance, Neoplasm , Humans , Male , Myofibroblasts/drug effects , Myofibroblasts/pathology , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/pathology , Oncogene Proteins, Fusion/genetics , Protein-Tyrosine Kinases/genetics , Proto-Oncogene Proteins/genetics , Pyrazoles/administration & dosage , Pyridines/administration & dosage , Pyrimidines/administration & dosage , Receptor, Platelet-Derived Growth Factor beta/genetics , Sarcoma/genetics , Sarcoma/pathology , Standard of Care , Sulfones/administration & dosage
13.
Skin Res Technol ; 4(2): 79-82, 1998 May.
Article in English | MEDLINE | ID: mdl-27332103

ABSTRACT

BACKGROUND/AIMS: One clinical sign of photodamage is a sallow discolouration of the skin, and solar elastotic degenerative change in the upper dermis may cause this change. We have attempted to quantify these phenomena and relate them to each other and to age. METHODS: Twenty-seven healthy volunteers (age 18 to 61 years) were recruited. We examined the back of the hand of photodamaged individuals and the inner upper arm to demonstrate changes due to ageing. Each site was assessed for cutaneous blood flux using a laser Doppler fluxmeter (PF4000, Perimed UK), and for melanin pigmentation using a Melanin Index meter (Dermotronics Ltd, Cardiff, UK). Skin colour was measured using a diode array spectrophotometer (MCPD-1000, Photal, Japan), which computes CIE coordinates L*, a*, b*. Biopsies from each site were obtained from 13 of the subjects and were processed and stained with Gomori's aldehyde fuchsin. The percentage area of elastic staining material in the dermis was measured using image analysis. Sections were measured in four bands of 200 micron depth, and four fields were measured per band. RESULTS: Neither melanin content nor skin blood flux correlated with age for either skin site. Percentage area of elastosis correlated with age on the exposed site from the uppermost 600 microns of the dermis, (<200 micron depth, r=0.74, P<0.01, 200

14.
Skin Res Technol ; 1(1): 3, 1995 Feb.
Article in English | MEDLINE | ID: mdl-27328211
16.
Bone Marrow Transplant ; 51(6): 771-7, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26752137

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cell Transplantation/mortality , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/therapy , Adult , Aged , Disease-Free Survival , Female , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Myelodysplastic Syndromes/chemically induced , Myelodysplastic Syndromes/mortality , Recurrence , Survival Rate , Young Adult
17.
Leukemia ; 29(10): 2062-8, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26228813

ABSTRACT

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.


Subject(s)
Adrenal Cortex Hormones/pharmacology , Drug Resistance, Neoplasm/drug effects , Graft vs Host Disease/drug therapy , Hematologic Neoplasms/complications , Hematopoietic Stem Cell Transplantation/adverse effects , Pyrazoles/therapeutic use , Salvage Therapy , Adult , Aged , Animals , Disease Models, Animal , Female , Follow-Up Studies , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Hematologic Neoplasms/therapy , Humans , Janus Kinases/antagonists & inhibitors , Male , Mice , Middle Aged , Neoplasm Staging , Nitriles , Prognosis , Pyrimidines , Recurrence , Retrospective Studies , Survival Rate , Transplantation, Homologous , Young Adult
18.
Bone Marrow Transplant ; 50(5): 690-5, 2015 May.
Article in English | MEDLINE | ID: mdl-25774594

ABSTRACT

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.


Subject(s)
Antimetabolites, Antineoplastic/administration & dosage , Azacitidine/administration & dosage , Leukemia, Myeloid, Acute/therapy , Remission Induction , Stem Cell Transplantation , Adult , Aged , Allografts , Female , Humans , Male , Middle Aged , Retrospective Studies
19.
Ann Hematol ; 94(6): 981-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25645656

ABSTRACT

Transformation of follicular lymphoma (FL) into aggressive disease and relapse of de novo diffuse large B cell lymphoma (DLBCL) are considered highly unfavourable events. However, most published data were acquired when rituximab was not routinely used. We retrospectively analysed 50 patients with transformed FL (tFL) in a multicenter study and compared them to 50 individuals with relapsed DLBCL (rDLBCL) who all obtained rituximab for the treatment of their disease. Our goal was to identify factors that predict a more favourable prognosis. After a median follow-up of 5.4 years from diagnosis, there was no significant difference in median overall survival (OS) from the date of transformation (tFL) or date of the first relapse (rDLBCL) (1.9 versus 3.9 years, P = .542). Of note, 5-year OS of patients with tFL was 46 %. Follicular lymphoma patients, treatment naïve prior to transformation, fared significantly better than pretreated patients (median not reached versus 1.4 years, P = .014). Regarding rDLBCL, female gender (13.9 versus 1.8 years, P = .019) and absence of rituximab prior to the first relapse (14.0 versus 1.8 years, P = .035) were favourable prognostic factors in a uni- and multivariate analysis. Only a proportion of patients received high-dose chemotherapy with autologous stem cell transplantation (HDT-ASCT), i.e. 38 and 52 % of patients with tFL and rDLBCL, respectively. Our data indicate that a favourable prognosis is conferred by treatment naivety in tFL and by rituximab naivety in rDLBCL. In contrast, we did not find a prognostic impact of HDT-ASCT in our series.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, Follicular/diagnosis , Lymphoma, Follicular/drug therapy , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Aged , Female , Follow-Up Studies , Humans , Lymphoma, Follicular/mortality , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Retrospective Studies , Survival Rate/trends , Treatment Outcome
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