Emerging echinocandin-resistant Candida albicans and glabrata in Switzerland

Abstract Echinocandins represent the first-line therapy of candidemia. Echinocandin resistance among Candida spp. is mainly due to acquired FKS mutations. In this study, we report the emergence of FKS-mutant Candida albicans/glabrata in Switzerland and provide the microbiological and clinical characteristics of 9 candidemic episodes. All patients were previously exposed to echinocandins (median 26 days; range 15–77). Five patients received initial echinocandin therapy with persistent candidemia in 4 of them. Overall mortality was 33%.

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Danazol As First-Line Therapy for Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v128.22.5528.5528 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5528-5528

Author(s):

Perla Rocío Colunga-Pedraza ◽

Alejandra Garza-Ledezma ◽

Julia Colunga-Pedraza ◽

Olga Cantu-Rodriguez ◽

Rosa Elena Lozano-Morales ◽

...

Keyword(s):

Platelet Count ◽

Blood Cell ◽

Board Of Directors ◽

Neutrophil Count ◽

Clinical Characteristics ◽

Refractory Anemia ◽

First Line ◽

Advisory Committees ◽

First Line Therapy ◽

Line Therapy

Abstract Introduction: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematological disorders characterized by ineffective hematopoiesis and variable degrees of peripheral cytopenias. Neither curative nor standard therapy has been available yet for the majority of patients with MDS. Patients with available matched donor may undergo an allogeneic bone marrow transplant with a potential cure rate 30-50%. Danazol is a synthetic anabolic steroid with properties similar to corticosteroids, such as inhibition of interleukin-1 and TNF-α production. Also, has demonstrated activity in immune cytopenias and aplastic anemia but its efficacy in MDS has shown contradictory results. Recently there has been increasing interest in telomere dysfunction in hematological diseases. Short telomeres are the major prognostic risk factor for clonal evolution to myelodysplasia and acute leukemia. Danazol not only prevents telomere loss, but a mean increase occurs with improvement observed early during the course of hormone therapy. In our center with poor access to new strategies and therapies the use of danazol remains as an attractive option for patients with MDS because of its low cost. In this study we aim to document the clinical evolution of patients diagnosed with MDS treated with danazol as first-line therapy in our institution. Methods: We include patients diagnosed with MDS according to WHO criteria treated with danazol between 2005 and 2015. Response was defined as one or more of the following criteria: a rise in the platelet count >25 x 109/I, an increase in hemoglobin >2 g/dl or disappearance of a previous requirement for red blood cell transfusion, or an increase in neutrophil count >0.5 x 109/L. All patients received packed red blood cell and platelet transfusions according to physician criteria. Patients were given intravenous or oral antibiotics as needed as prophylaxis. Criteria for stop danazol included: no response to treatment, toxicity or patient's refusal to continue treatment. Blood counts were preformed at least 1-month intervals for the first 4 months. We compared those who responded versus no responders using the Student's t test or Mann-Whitney U test as corresponded. Results: Forty-two patients with MDS were treated with danazol. Median follow-up was 12 months (range 3-75). Median dose used was 400 mg (range 100-600) orally in two divided doses. Mean duration of treatment for all patients was 6 months (range 3-72 months). The distribution by WHO subtypes included 26 refractory cytopenia with multilineage dysplasia (RCMD) (62%), 6 patients with refractory cytopenia with unilineage dysplasia (RCUD), 6 refractory anemia with excess blasts (RAEB), 2 refractory anemia with ring sideroblasts (RARS) and 1 MDS associated with isolated del(5q). Twenty-four (60%) patients presented clinical response. Response for patients with anemia was 23.8% (10/24), increase in absolute neutrophil count occurred in 36.8% (7/19), and 60% (24/40) presented an increase in platelet count. Time to initial response was 2 months (range, 1-8) while time to better response of 3 month (range, 1-8). Response was not associated to any MDS classification or administrated dose. Toxicity was mild and danazol was not discontinued in any patient. Side effects included three patients with gastrointestinal symptoms, and 4 patients reported weight gain. Median overall survival was 24 months (CI95% 5.1-42). Fifteen patients died (35.7%). Five patients progressed to AML. Conclusion: Different agents have been used in MDS. However, for the majority of patients with MDS no curative treatment exists. In conclusion our data suggest that Danazol may be effective in MDS with minimal toxicity, especially in patients with thrombocytopenia. Response was independent of severity, WHO classification and administrated dose. Table Clinical characteristics of responders versus non-responders Table. Clinical characteristics of responders versus non-responders Disclosures Gomez-Almaguer: Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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Patients with non-small-cell lung cancer harbouring a BRAF mutation: a multicentre study exploring clinical characteristics, management, and outcomes in a real-life setting: EXPLORE GFPC 02-14

Current Oncology ◽

10.3747/co.25.3945 ◽

2018 ◽

Vol 25 (5) ◽

Cited By ~ 6

Author(s):

J. B. Auliac ◽

S. Bayle ◽

A. Vergnenegre ◽

H. Le Caer ◽

L. Falchero ◽

...

Keyword(s):

Clinical Characteristics ◽

Real Life ◽

Stage Iv ◽

Small Cell ◽

Second Line ◽

Small Cell Lung ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Nsclc Patients

Background Mutations in BRAF are rare oncogene mutations, found in 2% of non-small-cell lung cancers (nsclcs). Little information is available about the management of patients with BRAF-mutated nsclc, except for those included in clinical trials. We undertook the present study to assess the clinical characteristics, management, and outcomes of those patients in a real-life setting.MethodsThis retrospective multicentre observational study included all patients with BRAF-mutated nsclc diagnosed between January 2012 and December 2014.ResultsPatients (n = 59) from 24 centres were included: 57.6% men; mean age: 64.5 ± 14.5 years; 82% with a performance status of 0–1 at diagnosis; smoking status: 40.3% current, 32.6% former; 93% with adenocarcinoma histology; 75% stage iv; 78% with V600E mutations; 2 with EGFR and 2 with ALK co-mutations. Of the stage iv patients, 79% received first-line therapy (14.2% anti-BRAF), and 48% received second-line treatment (23.8% anti-BRAF). Response rate and progression-free survival were, respectively, 51.7% and 8.7 months [95% confidence interval (ci): 6.4 months to 15.2 months] for first-line therapy and 35.3% and 4.1 months (95% ci: 2 months to 10.9 months) for second-line treatments. The 2-year overall survival was 58.5% (95% ci: 45.8% to 74.8%). Outcomes in patients with stage iv nsclc harbouring BRAF V600E mutations (n = 32) did not differ significantly from those of patients with other BRAF mutations.ConclusionsIn this real-world analysis, most nsclc patients with a BRAF mutation were men and current or former smokers. Survival appears to be better in these BRAF-mutated patients than in nsclc patients without an oncogenic driver.

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Preliminary Analysis of Clinical Characteristics of Patients Enrolled in the HD01 Protocol: A Randomised Trial of High Dose Therapy and Autologous Stem Cell Transplantation Versus Conventional Therapy for Patients with Advanced Hodgkin's Disease Responding to First Line Therapy

Leukemia & Lymphoma ◽

10.3109/10428199509052710 ◽

1995 ◽

Vol 15 (sup1) ◽

pp. 63-66 ◽

Cited By ~ 2

Author(s):

Massimo Federico ◽

Vera Clo ◽

Angelo M. Carella

Keyword(s):

Stem Cell ◽

Preliminary Analysis ◽

Clinical Characteristics ◽

Randomised Trial ◽

High Dose ◽

First Line ◽

High Dose Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Advanced Hodgkin’S Disease

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Aspirin Use and Survival in Multiple Myeloma Patients

Blood ◽

10.1182/blood-2018-99-113025 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3250-3250 ◽

Cited By ~ 1

Author(s):

Catherine R. Marinac ◽

Graham A Colditz ◽

Bernard Rosner ◽

Irene M. Ghobrial ◽

Brenda M Birmann

Keyword(s):

Multiple Myeloma ◽

Clinical Data ◽

Cox Proportional Hazards ◽

Health Study ◽

First Line ◽

Use Patterns ◽

First Line Therapy ◽

Line Therapy ◽

Overall Mortality

Abstract Background: Multiple myeloma (MM) is a lethal malignancy with 5- and 10-year survival rates of 46.7% and 20.6%, respectively. Marked advancements in treatment have improved survival within the last decade but are expensive and do not achieve cure. It is known that inflammation is important in MM pathogenesis, and regular aspirin use has been shown to confer a reduced risk of incident MM. However, the influence of aspirin on survival after diagnosis of MM is unknown. We investigated this question prospectively in two large cohorts. Methods: We identified 567 men and women diagnosed with MM between 1980 and 2012 in the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). Participants in both cohorts reported aspirin intake biennially on follow-up questionnaires beginning in 1986 in HPFS and 1980 in NHS. Using multivariable Cox proportional hazards regression models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for MM-specific and overall mortality through 2015 according to aspirin use patterns. We also examined differences in MM clinical characteristics by aspirin use patterns in a subset of participants with available clinical data. Results: After a median follow-up of 40 months, there were 135 total deaths (76%) and 107 MM−specific deaths (60%) among 177 participants who used aspirin after MM diagnosis, compared with 222 total deaths (90%) and 195 MM−specific deaths (79%) among 247 participants who did not use aspirin. Compared with nonusers, participants who used aspirin after diagnosis had a multivariable HR for MM−specific mortality of 0.55 (95% confidence interval [CI], 0.41, 0.73) and for overall mortality of 0.58 (95% CI, 0.45, 0.75), after adjustment for age at diagnosis, year of diagnosis, sex, body mass index, pre-diagnosis aspirin use, and number of comorbidities. We also observed evidence of a dose response association between postdiagnosis aspirin quantity for both MM-specific and overall mortality (P-trend <0.01). The association between postdiagnosis aspirin use and MM-specific and overall mortality were not materially different in models that excluded deaths that occurred within 12 months of completing the postdiagnosis aspirin assessment. We could not adjust for first line therapy, but adjustment for year of diagnosis may partially control for first line therapy in these cohorts. In a subsample (n=225) of participants with clinical data available, we did not observe statistically significant differences in the clinically presenting features of MM by post diagnosis aspirin use. We also did not observe statistically significant associations between pre-diagnosis quantity or duration of aspirin use and MM-specific or overall mortality. Conclusions: Although lack of adjustment for clinical parameters is a limitation, the findings suggest that aspirin use after MM diagnosis is associated with a lower risk of MM−specific and overall mortality. Disclosures Ghobrial: Celgene: Consultancy; BMS: Consultancy; Janssen: Consultancy; Takeda: Consultancy.

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Clinical Characteristics and Treatment Outcome of Refractory Cytopenia of Childhood (RCC): A Prospective Registration Through the Japanese Society of Pediatric Hematology

Blood ◽

10.1182/blood.v118.21.2781.2781 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2781-2781

Author(s):

Daisuke Hasegawa ◽

Xiaojuan Chen ◽

Shinsuke Hirabayashi ◽

Yasushi Ishida ◽

Shizuka Watanabe ◽

...

Keyword(s):

Bone Marrow ◽

Clinical Characteristics ◽

Who Classification ◽

Japanese Society ◽

Normal Karyotype ◽

First Line ◽

Monosomy 7 ◽

Pediatric Hematology ◽

First Line Therapy ◽

Line Therapy

Abstract Abstract 2781 Introduction: Refractory cytopenia of childhood (RCC) is a subtype of myelodysplastic syndrome (MDS) in children proposed by the World Health Organization (WHO) classification, which is characterized by dysplastic features of hematopoiesis and persistent cytopenia without increased blasts in bone marrow and peripheral blood. Recommendation of the treatment options for RCC, such as immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (SCT), has been proposed base on transfusion dependency, karyotype and the availability of donors. In this study, we retrospectively analyzed clinical characteristics and the outcome of 75 children with RCC and discussed the utility of treatment modalities. Patients and Methods: Of 222 children with MDS younger than 16 years of age, who were prospectively registered to the Japanese Society of Pediatric Hematology between 1999 and 2008, 75 children were diagnosed with RCC according to the WHO classification and were eligible for analysis. The median age at diagnosis was 7.9 years. Three-fourths of the patients showed cytopenia in multiple lineages. Hypoplastic BM was documented in 74% of the biopsy specimens. Forty-two patients (56%) had normal karyotype, 9 patients (12%) had chromosome 7 abnormalities, and 18 patients (24%) had other abnormal karyotype. As a first-line therapy, 25 patients received SCT and 22 patients IST, respectively. In the SCT group, 14 patients received total-body irradiation as a conditioning regimen. Twenty-six patients who were not transfusion dependent or severely neutropenic were followed without treatment (Watch and Wait; W&W). Patients were divided into 2 subgroups according to the severity of dysplasia in bone marrow: RCC with unilineage or multilineage dysplasia (RCC-UD: n=40, RCC-MD: n=35). The patients with RCC-MD showed hypoplastic BM less frequently (57%) and had monosomy 7 more frequently (20%) than those with the RCC-UD (88% and 5%, respectively). Proportion of patients with trisomy 8 was similar between RCC-UD and RCC-MD (10% and 9%). Outcome: The 5-year overall survival (OS) for all patients was 71+/−9%; 31+/−17% in the SCT group, 89+/−8% in the IST group and 100+/−0% in the W&W group. Only 1 patient in the W&W group progressed to advanced MDS 20 months after diagnosis. One patient suffered from relapse after IST. Transplant-related mortality (TRM) was the most common cause of treatment failure in SCT group. In the IST group, 15 patients (68%) including 5 patients who had chromosome abnormalities responded. Cyclosporine (CSA) alone induced comparable response with combination of CSA and anti-thymocyte globulin (6/10 and 9/12, respectively; p=0.65). Of 7 non-responders, 4 patients were rescued by the second-line SCT. In the W&W group, all children were alive and 1 patient suffered from disease progression. Two of 11 children with normal karyotype who underwent SCT died of TRM, whereas 5 of 7 children with monosomy 7 who received SCT died of TRM. There was no difference in OS at 5 years between RCC-UD and RCC-MD (73+/−9% and 72+/−12%, respectively; p=0.07). Conclusion: Disease progression and relapse were rare in this patient population. We did not observe a clear impact of severity of dysplasia on clinical outcome. Given a high rate of TRM, indication and conditioning regimens of SCT need to be reconsidered. Since IST, even CSA alone, was effective in more than half of the patients and showed a favorable survival rate also in non-responders, IST might be considered as a first-line therapy in a broader population of RCC. W&W strategy seems to be appropriate if patients do not suffer from severe cytopenia. Disclosures: No relevant conflicts of interest to declare.

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