Evidence-based Pharmacy Evaluation of 2-Chlorodeoxyadenosine in the Therapy of Pediatric Recurrent/Refractory Langerhans Cell Histiocytosis
XING Ya-bing1, MA Shu-li1, ZHANG Sheng-nan1, ZHANG Miao1, WANG Xiao-ling2*
1. Department of Pharmacy, Children′s Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China; 2. Department of Pharmacy, Beijing Children′s Hospital Affiliated to the Capital Medical University, Beijing 100045, China
Abstract：OBJECTIVE To evaluate the rationality of off-label drug use of cladribine in treatment of recurrent/refractory Langerhans cell histiocytosis in children. METHODS The latest edition of drug labels, clinical practice guideline about Langerhans cell histiocytosis (LCH) and rules for clinical medical were retrieved, to collect all indications of cladribine. And PubMed, Embase, Cochrane Library, Clinical trials, CNKI, CBM, VIP and Wanfang databases were searched from January 1, 1993 to March 27, 2020 to collect all public literatures involved cladribine in treatment of relapsed/refractory LCH in children. And then the efficacy and safety of the drug in treatment of relapsed/refractory LCH were reviewed systematically. RESULTS The latest instruction of cladribine was not approved that the drug could be used to treat LCH. However, two clinical guidelines recommending cladribine was used to treatment of recurrent/refractory LCH as second line regimen or salvage therapy. Although there were no randomized controlled trials (RCT) or well-designed nonrandomized controlled trials were found, there were 13 case series study articles were retrieved for efficacy and safety analysis. CONCLUSION Cladribine as monotherapy is significantly more effective in the treatment of patients with non-risk organ involved, but it is not sufficient to change the final fate of the patients with most severe disease. While, to date, is the best available salvage option for patients with recurrent/refractory diseases cladribine combined with cytarabine which showed extremely response rate and excellent 5-year predicted survival rate besides high treatment toxicity and required highest level of supportive therapy.
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