Article

A phase II trial using thalidomide for Langerhans cell histiocytosis.

Baylor College of Medicine, Texas Children's Cancer Center/Hematology Service, Houston, Texas, USA.
Pediatric Blood & Cancer (impact factor: 1.89). 02/2007; 48(1):44-9. DOI:10.1002/pbc.20578 pp.44-9
Source: PubMed

ABSTRACT Few new drugs for treatment of Langerhans cell histiocytosis (LCH) have been studied. Tumor necrosis factor-alpha (TNF-alpha) is a prime therapeutic target since it appears to be present in elevated amounts in LCH lesions. Thalidomide inhibits TNF-alpha production by affecting the gene promoter as well as other anti-cytokine effects.
A Phase II trial of thalidomide for treatment of LCH patients who had failed primary and at least one secondary regimen was conducted. Sixteen patients were enrolled: nine males and seven females ranging in age from 19 months to 45 years. Six patients were high risk (HR) because of spleen, liver, lung, or bone marrow involvement. The low risk (LR) patients included six with bone/skin LCH, one with multiple bone, one with skin/bone/pituitary, one with skin/bone/brain, and one with skin only disease involvement. Fifteen patients remained on treatment from 3 weeks to over 1 year.
Among the LR patients there were four complete responses, three partial responses, and two with no response to thalidomide. No HR patient responded to thalidomide and all died of pulmonary, liver, or bone marrow failure. Thalidomide may have played a role in the pulmonary failure. Other toxicities that required stopping therapy included neutropenia, peripheral neuropathy, and fatigue.
Thalidomide is an effective therapy for some LR patients with LCH, but showed no significant responses in HR patients. Dose-limiting toxicities may reduce its efficacy in LR patients. Additional trials with improved anti-TNF therapies would appear warranted.

0 0
 · 
0 Bookmarks
 · 
27 Views
  • Source
    Article: Langerhans cell histiocytosis: a review of the current recommendations of the Histiocyte Society.
    Elizabeth K Satter, Whitney A High
    [show abstract] [hide abstract]
    ABSTRACT: Langerhans cell histiocytosis is a rare proliferative disorder where pathologic Langerhans cells accumulate in a variety of organs. Historically, the nomenclature regarding this entity has been confusing because the disease had been subcategorized simply based upon the different clinical manifestations. In the following article, we summarize the current recommendation of the Histiocyte Society regarding the classification, evaluation, prognosis, and treatment of Langerhans cell histiocytosis.
    Pediatric Dermatology 04/2008; 25(3):291-5. · 1.07 Impact Factor
  • Source
    Article: Clinical characteristics and survival of children with Langerhans cell hystiocytosis
    Nada Krstovski, Dragana Janić, Lidija Dokmanović, Radivoj Brdar
    [show abstract] [hide abstract]
    ABSTRACT: INTRODUCTION Langerhans cell histiocytosis is a rare disease in children, initial presentation is variable, clinical course, prognosis and survival are mostly unpredictable. OBJECTIVE To summarise clinical characteristics and treatment results in children with Langerhans cell histiocytosis. METHOD Retrospectively there were analyzed patients with LCH diagnosed and treated at Hematology Department of University Children's Hospital in Belgrade from 1990 to 2006. Clinical presentation, therapy and survival according to Kaplan-Meier's statistical test was analysed. RESULTS 30 patients were treated, aged from 4 months to 14 years, mean 3.9 years, median 2.3 years, 18 (60%) males, 12 (40%) females. A single system disease was diagnosed in 16 (53%) patients, of whom 6 patients with multifocal bone disease. All patients were in complete remission averagely following162 and 82 months respectively. Multisystem disease was found in 14 (47%) patients. The lymph nodes and skin were more frequently involved organs than the central nervous system (diabetes insipidus), lung, liver and spleen. The number of involved organs ranged from 2 to 8, mean 4.2. Four patients died due to disease progression 3, 16, 36 and 66 months after diagnosis. Nine patents with multisystem disease were in remission with 117 months of follow-up. One patient was lost on follow-up. CONCLUSION The clinical course of patients with a single system disease is usually benign while a multisystem disease has to be aggressively treated with precise initial evaluation and staging before therapy.
    Srpski Arhiv za Celokupno Lekarstvo. 01/2008;
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

1 year
 
19 months
 
Additional trials
 
bone marrow involvement
 
bone/skin LCH
 
Dose-limiting toxicities
 
effective therapy
 
HR patient
 
HR patients
 
Langerhans cell histiocytosis
 
LCH patients
 
low risk
 
LR patients
 
partial responses
 
Phase II trial
 
prime therapeutic target
 
significant responses
 
skin/bone/pituitary
 
Thalidomide inhibits TNF-alpha production
 
Tumor necrosis factor-alpha
 

Kenneth L McClain