scholarly journals Vemurafenib for Refractory Multisystem Langerhans Cell Histiocytosis in Children: An International Observational Study

2019 ◽  
Vol 37 (31) ◽  
pp. 2857-2865 ◽  
Author(s):  
Jean Donadieu ◽  
Islam Amine Larabi ◽  
Mathilde Tardieu ◽  
Johannes Visser ◽  
Caroline Hutter ◽  
...  
Keyword(s):  
Adverse Events ◽  
Disease Activity ◽  
Langerhans Cell Histiocytosis ◽  
Disease Activity Score ◽  
Evaluation Criteria ◽  
Langerhans Cell ◽  
Activity Score ◽  
Organ Involvement ◽  
Hematopoietic Stem

PURPOSE Off-label use of vemurafenib (VMF) to treat BRAFV600E mutation–positive, refractory, childhood Langerhans cell histiocytosis (LCH) was evaluated. PATIENTS AND METHODS Fifty-four patients from 12 countries took VMF 20 mg/kg/d. They were classified according to risk organ involvement: liver, spleen, and/or blood cytopenia. The main evaluation criteria were adverse events (Common Terminology Criteria for Adverse Events [version 4.3]) and therapeutic responses according to Disease Activity Score. RESULTS LCH extent was distributed as follows: 44 with positive and 10 with negative risk organ involvement. Median age at diagnosis was 0.9 years (range, 0.1 to 6.5 years). Median age at VMF initiation was 1.8 years (range, 0.18 to 14 years), with a median follow-up of 22 months (range, 4.3 to 57 months), whereas median treatment duration was 13.9 months (for 855 patient-months). At 8 weeks, 38 complete responses and 16 partial responses had been achieved, with the median Disease Activity Score decreasing from 7 at diagnosis to 0 ( P < .001). Skin rash, the most frequent adverse event, affected 74% of patients. No secondary skin cancer was observed. Therapeutic plasma VMF concentrations (range, 10 to 20 mg/L) seemed to be safe and effective. VMF discontinuation for 30 patients led to 24 LCH reactivations. The blood BRAFV600E allele load, assessed as circulating cell-free DNA, decreased after starting VMF but remained positive (median, 3.6% at diagnosis, and 1.6% during VMF treatment; P < .001) and was associated with a higher risk of reactivation at VMF discontinuation. None of the various empirical therapies (hematopoietic stem-cell transplantation, cladribine and cytarabine, anti-MEK agent, vinblastine, etc) used for maintenance could eradicate the BRAFV600E clone. CONCLUSION VMF seemed safe and effective in children with refractory BRAFV600E-positive LCH. Additional studies are needed to find effective maintenance therapy approaches.

scholarly journals Langerhans cell histiocytosis: An enigmatic disease

2019 ◽  
Vol 08 (03) ◽  
pp. 183-185
Author(s):  
Anubha Jain ◽  
Sushil Kumar ◽  
Priyanka Aggarwal ◽  
Mohan Kumar ◽  
Vineeta Gupta
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Bone Diseases ◽  
Langerhans Cell ◽  
Organ Involvement ◽  
Laboratory Findings ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Bony Involvement ◽  
Disseminated Disease

Abstract Background: Langerhans cell histiocytosis (LCH) is a poorly understood disease with heterogeneous clinical presentation ranging from unifocal bony involvement to disseminated disease with life-threatening complications. Materials and Methods: The clinical profile, laboratory findings, treatment, and long-term outcome were retrieved from maintained medical records from January 2006 to January 2016 and were retrospectively analyzed. The extent of the disease was classified as per the LCH-III trial of “The Histiocyte Society.” The assessment and categorization of treatment response followed LCH III trial definitions. Results: A total of 28 children with LCH were diagnosed. The age ranged between 5 months and 9 years, with a mean of 3½ years. The M: F ratio was 3:1. Single system, unifocal and multifocal bone diseases were seen in nine (32.1%) and two (7.1%) cases, respectively. Disseminated disease without risk organ involvement was seen in six (21.1%), whereas disseminated disease with risk organ involvement was seen in 11 (39.3%) cases. The most common presentation was bony involvement (19 [67.8%]), out of which 16 (88.8%) had skull involvement. During follow-up, 17 (60.7%) were in complete remission though five (17.8%) of them relapsed, but achieved second remission. Two (7.1%) were lost to follow-up. Six (21.4%) had progressive disease of which four expired and two abandoned treatment. Two (10.7%) refused the initiation of treatment. Conclusion: A better understanding of the disease, early suspicion, and diagnosis can improve the outcome of patients with LCH.

Disease course and late sequelae of Langerhans' cell histiocytosis: 25-year experience at the University of California, San Francisco.

1996 ◽  
Vol 14 (7) ◽  
pp. 2073-2082 ◽  
Author(s):  
B Willis ◽  
A Ablin ◽  
V Weinberg ◽  
S Zoger ◽  
W M Wara ◽  
...  
Keyword(s):  
San Francisco ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
Organ Involvement ◽  
Hormone Deficiency ◽  
Disease Course ◽  
Late Sequelae ◽  
Treatment Needs ◽  
Skeletal Defects

PURPOSE The purpose of our investigation was to correlate the extent and degree of organ involvement at presentation of Langerhans' cell histiocytosis (LCH) with subsequent disease course, survival, and late sequelae. MATERIALS AND METHODS The medical records of 71 patients with a pathologic diagnosis of LCH, age 0 to 21 years, who presented between January 1, 1969 and June 30, 1994, were reviewed for organ involvement at diagnosis, treatment, disease course, and late sequelae. Supplementary data were obtained by mailed questionnaire. RESULTS The median follow-up time from diagnosis for all patients was 8.1 years. Involvement at diagnosis included nine patients with skin-only disease, 22 with monostotic disease, 12 with polyostotic disease, and 28 with multisystem presentation. Treatment was surgery only in 17 and chemotherapy and/or radiotherapy in 54 patients. Recurrences were seen in 35 patients, with the highest rate in the polyostotic group. Ten patients died: seven with the multisystem presentation, two with monostotic disease, and one with skin-only disease. Causes included progressive LCH (n = 6) and late sequelae of either treatment (n = 3) or disease (n = 1). Late sequelae were seen in 64% of 51 patients with more than 3 years of follow-up data. The most common were skeletal defects in 42%, dental problems in 30%, diabetes insipidus in 25%, growth failure in 20%, sex hormone deficiency in 16%, hypothyroidism in 14%, hearing loss in 16%, and other CNS dysfunction in 14%. The overall estimated survival rates at 5, 15, and 20 years are 88%, 88%, and 77%, with an estimated event-free survival rate of only 30% at 15 years. CONCLUSION Despite the favorable survival, more than half of LCH patients will have further dissemination of disease or late sequelae, including even some patients with single-system disease at diagnosis. Future treatment needs to be designed to prevent disease progression and late sequelae.

Quantification and phenotype of regulatory T cells in rheumatoid arthritis according to Disease Activity Score-28

Autoimmunity ◽  
2009 ◽  
pp. 1-1
Author(s):  
Jose Miguel Sempere-Ortells ◽  
Vicente Perez-Garcia ◽  
Gema Marin-Alberca ◽  
Alejandra Peris-Pertusa ◽  
Jose Miguel Benito ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Score

Evaluation of Toll-like Receptor 2 Gene Expression in Rheumatoid Arthritis and Correlation with the Disease Activity

2019 ◽  
Vol 13 (2) ◽  
pp. 140-148
Author(s):  
Mai Nasser ◽  
Noha M. Hazem ◽  
Amany Atwa ◽  
Amina Baiomy
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Mrna Expression ◽  
Disease Activity Score ◽  
Activity Score ◽  
Tlr2 Expression ◽  
Positive Correlation ◽  
Tlr2 Mrna

Background: Rheumatoid Arthritis (RA) is an autoimmune, chronic, and systematic disease. It affects joints and bones. The exact etiology of RA is still unclear. Varied genetic and environmental factors have been associated with the increased risk for RA. Overactivation of Toll-Like Receptors (TLRs) could initiate the development of autoimmune diseases including RA. Objective: The aim of the study was to evaluate TLR2 gene expression in rheumatoid arthritis patients and investigate its correlation with the disease activity. Materials and Methods: This study included 60 patients and 20 healthy individuals. The patients were diagnosed with RA according to the 2010 American College of Rheumatology/ European League Against Rheumatism criteria (ACR/EULAR). All included subjects did not have any joint disorders and /or autoimmune diseases. RA disease activity was determined by the disease activity score of 28 joints. Whole blood was collected from all participants. Total RNA extraction was done. TLR2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR). Results: TLR2 mRNA expression was found to be significantly higher in RA patients compared to healthy controls. Also, a strong positive correlation was found between TLR2 expression level and the disease activity score. A non significant positive correlation was found between TLR2 expression and serum Rheumatoid Factor (RF) level. Conclusion: TLR2 pathway may have an important role in RA pathogenesis and could be a new biomarker for diagnosis and monitoring disease activity.

Anti-carbamylated Protein Antibodies and Serum Level of 14-3-3 Protein for Early Detection of Rheumatoid Arthritis Patient in Correlation with Rheumatoid Factor, Anti-CCP Antibodies, Disease Activity and Joint Damage using High Frequency Musculoskeletal Ultrasound

2020 ◽  
Vol 7 (2) ◽  
pp. 141-153
Author(s):  
Sahar A. Ahmed ◽  
Enas M. Darwish ◽  
Walaa A. Attya ◽  
Mai Samir ◽  
Mennatallah Elsayed ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Rheumatoid Factor ◽  
Disease Activity Score ◽  
Joint Damage ◽  
Musculoskeletal Ultrasound ◽  
Activity Score ◽  
Das 28 ◽  
Significant Difference ◽  
Hands And Feet

Background: Rheumatoid arthritis (RA) is a common progressive chronic inflammatory autoimmune disease which affects mostly small joints, causing pain, swelling, deformity, and disability. Although progress has been made in exploring RA nature, still there is a lot to know about the disease pathogenesis, diagnosis, and treatment. Aim of the Work: To investigate the role of serum anti-carbamylated protein antibodies and 14-3-3η in the diagnosis of RA compared to rheumatoid factor (RF), anti-CCP antibodies, and highfrequency musculoskeletal ultrasound used to assess the disease activity and joint damage. Methods: Serum anti-carbamylated protein antibodies and 14-3-3η were measured using ELISA in 61 RA patients and 26 normal controls. RA Disease Activity Score (DAS 28), X-ray and musculoskeletal ultrasound (hands and feet), carotid ultrasound (Intima-Media Thickness IMT) were used in assessing the RA disease. Results: Anti-carbamylated protein antibodies were significantly elevated in RA patients 4.5 (4.1- 8.9 U⁄ml) compared to the control 3.2(1.9- 4.3 U⁄ml) (p< 0.001) but 14-3-3η showed no significant difference. There was a significant positive correlation between anti-carbamylated protein antibodies, 14-3-3η levels and disease activity score assessed by DAS 28, increased IMT measured by carotid duplex, total synovitis and total erosion score were assessed by musculoskeletal ultrasound. There was no correlation between RF and anti-CCP antibodies. Anti-carbamylated protein antibodies were found to have 66.7% sensitivity and 85.2% specificity in RA diagnosis, while 14- 3-3η had 51.9% sensitivity and 72.1% specificity. Conclusion: Anti-carbamylated protein antibodies and 14-3-3η have a high sensitivity and specificity in RA diagnosis and had a correlation with the disease activity and joint damage.

OP0003 Development and Preliminary Validation of a Candidate Disease Activity Score for Gout

2013 ◽  
Vol 72 (Suppl 3) ◽  
pp. A48.3-A49 ◽  
Author(s):  
C. A. Scirè ◽  
C. Viroli ◽  
M. Manara ◽  
M. A. Cimmino ◽  
M. Govoni ◽  
...  
Keyword(s):  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Score ◽  
Preliminary Validation
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