scholarly journals First line treatment selection modifies disease course and long-term clinical outcomes in Mycobacterium avium complex pulmonary disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kiyoharu Fukushima ◽  
Seigo Kitada ◽  
Sho Komukai ◽  
Tomoki Kuge ◽  
Takanori Matsuki ◽  
...  
Keyword(s):  
Pulmonary Disease ◽  
Mycobacterium Avium ◽  
Propensity Scores ◽  
Cox Regression ◽  
Line Treatment ◽  
First Line ◽  
Standard Regimen ◽  
Cox Regression Analysis ◽  
First Line Treatment

AbstractThe combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by current guidelines have been reported. We undertook a single-centred retrospective cohort study to evaluate the long-term outcomes in 295 patients with MAC-PD following first line treatment with standard (RFP, EB, clarithromycin [CAM]) or alternative (EB and CAM with or without fluoroquinolones (FQs) or RFP, CAM, and FQs) regimens. In this cohort, 80.7% were treated with standard regimens and 19.3% were treated with alternative regimens. After heterogeneity was statistically corrected using propensity scores, outcomes were superior in patients treated with standard regimens. Furthermore, alternative regimens were significantly and independently associated with sputum non-conversion, treatment failure and emergence of CAM resistance. Multivariate cox regression analysis revealed that older age, male, old tuberculosis, diabetes mellitus, higher C-reactive protein, and cavity were positively associated with mortality, while higher body mass index and M. avium infection were negatively associated with mortality. These data suggest that, although different combination regimens are not associated with mortality, first line administration of a standard RFP + EB + macrolide regimen offers the best chance of preventing disease progression in MAC-PD patients.

Addition of Rituximab to Front-Line-Treatment Highly Improved the Outcome of Elderly Patients with Follicular Lymphoma: a Population Based-Study From the Modena Cancer Registry

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5077-5077
Author(s):  
Stefano Luminari ◽  
Irene Biasoli ◽  
Luigi Marcheselli ◽  
Monica Bellei ◽  
Alessandra Dondi ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Cox Regression ◽  
The Elderly ◽  
Population Based ◽  
Line Treatment ◽  
First Line ◽  
Population Based Study ◽  
Cox Regression Analysis ◽  
Second Period ◽  
First Line Treatment

Abstract Abstract 5077 Background: The benefit of adding Rituximab to combination chemotherapy in Follicular Lymphoma (FL) has been established in several randomized clinical trials (RCT). All of them have shown improvements in response rates, time to progression or overall survival (OS). The aim of the study was to assess the impact of the introduction of Rituximab in the treatment of FL in the general population of elderly patients, usually not included in RCT. Methods: All FL patients diagnosed in the province of Modena, Italy that had been diagnosed between 1997 and 2010 were identified from the archives of the Modena Cancer Registry that covers a population of approximately 600. 000 people. In the studied region Rituximab was available for first line treatment of FL since 2004. Therefore, for study purposes patients were grouped according to the year of diagnosis in 2 study periods (1997–2003, and 2004–2010). Elderly patients were defined using a cut off for age at 60 years. Clinical and treatment characteristics and also OS were compared according to the period of diagnosis and also, regarding the use or not of Rituximab as part of first line treatment. Moreover, a Cox regression analysis was performed to identify clinical factors and treatment characteristics associated with OS. Results: A total of 340 FL patients were identified of whom 177 (52%) were older than 60 years. No difference was found regarding clinical characteristics at diagnosis (age, gender, stage, bulky disease and LDH level) among study periods. Regarding treatment, no difference was found for the first general approach (watch and wait, chemotherapy or radiotherapy) across time. Among 229 patients initially treated with chemotherapy, antracyclines (ADM) or fludarabine (F)-based-regimens were the most frequently used. However, the use of ADM and/or F-based-regimens decreased from 82% (85/104) in the first period to 66% (83/125) in the last period (p=0. 03). Elderly patients (67%; 83/124) received less frequently ADM or F-based-regimens in comparison with younger patients (81%; 85/105) (P<0. 001). In contrast, the use of Rituximab alone or as part of front line treatment remarkably increased from 15% (16/104) in the first period to 94% (118/125) after 2003 (p<0. 001). This increase was also observed among elderly patients (8% (4/49) in the first period and 92% (69/75) in the last period, p<0. 001). After a median follow up of 68 months (range 8 to 176) for living patients, median OS was not reached. In univariate analysis factors associated with inferior OS were older age (>60), period of diagnosis before 2004, no use of Rituximab and abnormal LDH levels. The 5-years OS increased from 73% to 85% moving from first to second study periods (p=0. 008). In the Cox-Regression analysis, age > 60 (HR 11. 27 95%CI 5–25) and abnormal LDH level (HR 2. 7 95%CI 1. 56–4. 8) at diagnosis were identified as independent adverse risk factors. In contrast, the use of Rituximab yielded a protective effect (HR 0. 4 95%CI 0. 23–0. 79). In multivariate analysis period of diagnosis and use of Rituximab were mutually exclusive. Comparing young with elderly patients, only the latter group had a significant improvement in OS across the study periods: among the young, the 5-years OS in the first and second period was 89% and 98%, respectively, p= 0. 07; and among the elderly the 5-years OS in the first and second period was 58% and 72%, respectively p=0. 02. Conclusion: The present population based study showed a remarkable improvement in OS of FL patients after 2003, as a consequence of introduction of Rituximab as part of first line treatment. This improvement was mostly pronounced in the elderly population. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical and Biological Characteristics and Outcomes of Richter Transformation : A French Multicenter Study from the Filo Group

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4112-4112
Author(s):  
Charline Moulin ◽  
Romain Morizot ◽  
Thomas Remen ◽  
Hélène Augé ◽  
Florian Bouclet ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Intermediate Risk ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Long Term Survivors ◽  
First Line Treatment

Introduction: About 2 to 10% of patients (pts) diagnosed with Chronic Lymphocytic Leukemia (CLL) develop diffuse large B-cell lymphoma (DLBCL, so-called Richter transformation (RT)) over long-term follow-up. The outcomes of pts with RT are variable and poorly understood and there is no consensus on the best therapeutic approach. The aim of this study was to analyze the clinical characteristics, outcomes and factors predictive of survival in a large series of RT from the French Innovative Leukemia Organization (FILO). Methods: Biopsy-confirmed RT (limited to DLBCL and excluding Hodgkin lymphoma) diagnosed from 2001 to 2018 were identified from eight FILO centers. Clinical and biological characteristics of CLL and RT at diagnosis, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) analyzed by immunohistochemistry and RT score (Tsimberidou AM et al, J Clin Oncol, 2006) were analyzed as well as treatment and outcomes. Overall survivals (OS) were defined as time from CLL and RT diagnosis to death from any cause and analyzed using the Kaplan-Meier method. Statistical analyses were performed with SAS version 9.4. Results: A total of 70 CLL pts who developed RT were identified. The median age at CLL diagnosis was 62 years old (range 35-82), and 50 (71.4 %) were male. The median time to transformation was 5.5 years (range 0 to 22 years), with 12 simultaneous diagnosis of CLL and RT. Prior to RT, 20 (29%) pts had not been treated for CLL, 50 received one (n=21) or more (n= 29) line of treatment ; 6 pts had received a novel agent (ibrutinib, idelalisib or venetoclax). The median age at RT diagnosis was 68 years old (range 42-88). All biopsies were centrally reviewed; 38/58 pts (66%) had elevated LDH (>1.5N) ; 35/65 pts (54 %) had bulky disease (≥ 5 cm); 10/54 (18.5%) pts had del(17p) or TP53 mutation ; 9/42 pts (21%) had a complex karyotype (at least 3 abnormalities). The CLL and RT were clonally related in 27/27 (100%) tested pts. COO by Hans algorithm was non germinal center B cell-like (GCB) in 26/28 pts (93%). EBV was positive or detected in 5/40 (12.5%) pts. The median of Ki67 positivity was 70% (range 30% to 100%). The RT score (based at RT diagnosis on ECOG performance status 2-4, LDH >1.5 x normal, platelets<100 x 109/L, tumor size >5 cm and >1 prior therapy for CLL) was : low risk in 17 pts (31%), low-intermediate risk in 10 pts (19%), high-intermediate risk in 14 pts (25%) and high risk in 14 pts (25%). The most common first-line treatment of RT was immunochemotherapy (n=57, 87%) including R-CHOP-like regimen (n=48, 73%). Autologous or allogeneic transplantation was performed for 7 pts (11%). Response to first-line treatment was complete or partial response in 26 pts (40%), and stable disease or progression in 39 pts (60%). After a median follow-up of 8 years, 51/64 pts (80%) have died. The main causes of death were progressive DLBCL (n=36, 71%), infection (n=8, 16%) or progressive CLL (n=2, 4%). The median OS of the cohort from CLL and RT diagnosis (Figure 1) were 7.8 years and 9.5 months, respectively. In univariate analysis, patients with TP53 disruption at CLL stage, low platelets count, elevated LDH, elevated beta2-microglobulin, high ECOG score, high RT score, EBV positivity and absence of response to first-line RT treatment had worse OS. The ECOG score, platelets count and TP53 disruption remain significant in multivariate Cox-regression. Last, we compared the clinical and biological parameters of two Richter groups defined as: (i) short-term survivors (<12 months, n = 34) and (ii) long-term survivors (>48 months, n = 18). Long survival was significantly associated with elevated platelets count, low LDH, low ECOG, low RT score and response to RT first-line treatment. Discussion: The clinical outcomes of RT patients is poor and novel treatment options are needed. However, a group of long-term survivors was identified, characterized by elevated platelets count, low LDH, low ECOG, low RT score and response to immunochemotherapy. Disclosures Leblond: Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Cymbalista:Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Abbvie: Honoraria. Guièze:Abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria. Broseus:Janssen: Honoraria; Gilead: Honoraria; Novartis: Research Funding. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Severe aplastic anemia: allogeneic bone marrow transplantation as first-line treatment

2018 ◽  
Vol 2 (15) ◽  
pp. 2020-2028 ◽  
Author(s):  
George E. Georges ◽  
Kris Doney ◽  
Rainer Storb
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Marrow Transplantation ◽  
Severe Aplastic Anemia ◽  
Unrelated Donor ◽  
Line Treatment ◽  
First Line ◽  
Matched Unrelated Donor ◽  
First Line Treatment

Abstract Treatment of severe aplastic anemia has improved significantly over the past 4 decades. This review will summarize the key areas of progress in the use of allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive therapy (IST) for the treatment of aplastic anemia and then summarize the recommendations for first-line treatment. Based on recent data, we argue that guidelines for the initial treatment of patients with newly diagnosed severe aplastic anemia require revision. At the time of diagnosis, before beginning treatment, HLA typing should be done to identify a marrow donor among family members or in the unrelated donor registries, and a marrow transplant should be considered first-line therapy. The priority order of donor source for bone marrow transplantation is: (1) HLA-identical sibling, (2) HLA-matched unrelated donor, and (3) HLA-haploidentical donor if an HLA-matched unrelated donor is not rapidly available. Each of these donor marrow sources may be preferable to nontransplant IST. We make this recommendation because of the long-term persistent risk for disease relapse and secondary myelodysplastic syndrome or acute myeloid leukemia with the use of nontransplant IST for patients with aplastic anemia. In contrast, marrow transplantation is associated with high cure rates of aplastic anemia and a relatively low risk for graft-versus-host disease, with many patients now living for decades without the risk for disease recurrence or the development of clonal disorders. Implementation of this first-line treatment strategy will provide patients with severe aplastic anemia the best chance of long-term disease-free survival.

scholarly journals Lactate Dehydrogenase (LDH) Response to First-Line Treatment Predicts Survival in Metastatic Breast Cancer: First Clues for A Cost-Effective and Dynamic Biomarker

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1243 ◽  
Author(s):  
Giacomo Pelizzari ◽  
Debora Basile ◽  
Silvia Zago ◽  
Camilla Lisanti ◽  
Michele Bartoletti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lactate Dehydrogenase ◽  
Prognostic Factor ◽  
Metastatic Breast ◽  
Prognostic Impact ◽  
Line Treatment ◽  
First Line ◽  
Cox Regression Analysis ◽  
First Line Treatment

Background: Elevated plasmatic lactate dehydrogenase (LDH) levels are associated with worse prognosis in various malignancies, including metastatic breast cancer (MBC). Nevertheless, no data are available on the prognostic role of LDH as a dynamic biomarker during first-line treatment in unselected MBC. Methods: We reviewed data of 392 women with MBC to evaluate the association between LDH variation after 12 weeks of first-line treatment and survival. The prognostic impact was tested by multivariate Cox regression analysis. Results: Plasmatic LDH was confirmed as an independent prognostic factor in MBC. Patients who maintained elevated LDH levels after 12 weeks of first-line treatment experienced worse progression-free survival (PFS, HR 2.88, 95% CI: 1.40–5.89, p = 0.0038) and overall survival (OS, HR 2.61, 95% CI 1.16–5.86, p = 0.02) compared to patients with stable normal LDH levels, even after adjustment for other prognostic factors. Notably, LDH low-to-high variation emerged as an unfavorable prognostic factor for PFS (HR 3.96, 95% CI 2.00–7.82, p = 0.0001). Conclusions: Plasmatic LDH and its variation during first-line treatment predict PFS and OS in MBC, providing independent prognostic information. It would be worthwhile to prospectively evaluate the association between LDH variation and therapeutic benefit in MBC, and explore how it may affect treatment strategies.

scholarly journals Management of Pearly Penile Papules: A Review of the Literature

2019 ◽  
Vol 24 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Anthony D. Honigman ◽  
Danielle P. Dubin ◽  
Justin Chu ◽  
Matthew J. Lin
Keyword(s):  
Psychological Distress ◽  
Long Term Results ◽  
Treatment Modalities ◽  
Line Treatment ◽  
Review Of The Literature ◽  
First Line ◽  
Cosmetic Outcomes ◽  
First Line Treatment ◽  
Ablative Laser

Pearly penile papules (PPPs) are benign, dome-shaped lesions found around the corona of the penis. Despite being asymptomatic and benign in nature, the appearance of PPPs may cause a great deal of psychological distress to both the patient and their sexual partner. While patient reassurance may be the first-line treatment, several other treatment modalities including cryotherapy, electrodessication and curettage, and laser therapy have all been used to treat PPPs in order to achieve a cosmetic outcome that satisfies the patient. Based on the evaluation of the existing literature, ablative laser therapies offer satisfactory cosmetic outcomes with good long-term results.

scholarly journals Glucocorticoids in Graves’ orbitopathy: mechanisms of action and clinical application

2020 ◽  
Vol 11 ◽  
pp. 204201882095833
Author(s):  
Jan Längericht ◽  
Irene Krämer ◽  
George J. Kahaly
Keyword(s):  
Low Cost ◽  
Standard Of Care ◽  
Daily Basis ◽  
Clinical Severity ◽  
Line Treatment ◽  
First Line ◽  
Graves Orbitopathy ◽  
Meta Analyses ◽  
First Line Treatment

Background: Graves’ orbitopathy (GO) is the most frequent extrathyroidal manifestation of the autoimmune Graves’ disease. GO significantly impacts quality of life and has a psycho-social morbidity. Inflammation and swelling of the orbital tissue often leads to proptosis, diplopia, and decrease of visual acuity. Due to the inflammatory background of the disease, glucocorticoids (GC) have been used as a first-line treatment for decades. Methods: PubMed and MeSH database were searched for original articles, clinical trials, reviews, and meta-analyses published between 1 January 2000 and 31 March 2020 and pertaining to both the mechanism of action and immunological effects of GC as well as to the treatment of GO by GC. The publications were evaluated according to their setting and study design. Results: GC act through genomic (trans-activation and trans-repression) and rapid non-genomic mechanisms. GC in general, and the intravenous (IV) administration of GC in particular, markedly decrease the activity and number of the most potent antigen-presenting dendritic cells. According to the internationally acknowledged European Thyroid Association Guidelines for the management of GO, weekly IVGC application over 12 weeks is recommended as first-line treatment for patients with active and severe GO. The daily and cumulative dose should be tailored according to clinical severity, for example, 4.5 g of IV methylprednisolone for the inflammatory component versus 7.5 g in the presence of diplopia and severe proptosis. Fast and significant improvements in orbital symptoms and signs are noted in 65–70% of patients. Long-term experience over decades, and worldwide availability at low cost, underline the clinical and therapeutic relevance of GC. Adverse events are rarely severe, dose-dependent, and usually reversible, hence easy to handle by medical investigators. Oral GC application on a daily basis is characterized by high bioavailability but reduced efficacy and increased toxicity. Conclusion: IVGC still represents the standard of care in active/severe GO. Innovative biologicals, like monoclonal antibodies targeting the thyrotropin/Insulin-like growth factor-1 receptors or pro-inflammatory cytokines (e.g., Interleukin-6) should be compared with standard GC treatment with respect to short- and long-term efficacy, safety, costs, and global availability.

Blood platelet volume to predict treatment-specific outcomes of metastatic castration-resistant prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 242-242
Author(s):  
Wataru Fukuokaya ◽  
Takahiro Kimura ◽  
Fumihiko Urabe ◽  
Shoji Kimura ◽  
Kojiro Tashiro ◽  
...  
Keyword(s):  
Radiographic Progression ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Castration Resistant ◽  
Psa Progression ◽  
Pre Treatment ◽  
First Line Treatment

242 Background: In the present guidelines for the management of metastatic castration-resistant prostate cancer (CRPC), it is unclear who benefits from androgen receptor axis-targeted agents (ARATs) or docetaxel as a first-line treatment. Methods: We conducted a single-institutional retrospective study to explore treatment-specific biomarkers for treatment response of metastatic CRPC. A cohort of 211 patients with metastatic CRPC treated with either ARAT (abiraterone acetate or enzalutamide) or docetaxel as a first-line treatment was evaluated. In addition to well-established biomarkers such as hemoglobin, neutrophil-to-lymphocyte ratio, alkaline phosphatase, and lactate dehydrogenase, we also assessed red cell distribution width, platelet count, and mean platelet volume (MPV). Laboratory measures were assessed within 1 month before starting treatment. Prostate-specific antigen progression-free survival (PSA-PFS) and radiographic progression-free survival (RPFS) were evaluated. Multivariable Cox regression models were used to assess the association between biomarkers and the risk of events. We also studied the statistical interaction between biomarkers and clinical outcomes. Results: Of all blood-based biomarkers, multivariable Cox regression models identified pre-treatment MPV (≤9.0 fL) as an independent prognostic factor of both PSA progression (hazard ratio [HR]: 2.62, 95% confidence interval [CI]: 1.25-5.48, P = 0.011) and radiographic progression (HR: 4.46, 95% CI: 1.79-11.1, P = 0.001). In addition, these models showed a lower risk of PSA progression (HR: 0.38, 95% CI: 0.15-0.96, P = 0.041) and radiographic progression (HR: 0.16, 95% CI: 0.05-0.50, P = 0.002) with docetaxel compared with ARAT when pre-treatment MPV was small. Conclusions: The present study identified MPV as a significant treatment-specific prognostic factor of PSA progression and radiographic progression in patients with metastatic CRPC treated with a first-line treatment. Furthermore, our results suggested that small MPV was associated with superior survival benefit on docetaxel over ARAT.

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