Reduced doses of cladribine and cytarabine regimen was effective and well tolerated in patients with refractory‐risk multisystem Langerhans cell histiocytosis

Abstract

were re-imaged within the recommended time period had a shorter duration of oral antifungal therapy, emphasizing the importance of minimizing delayed imaging. Further collaborative studies would help to characterize stopping criteria in larger cohorts of patients. AcknowledgementsThis work was undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding Scheme. Author contributionsAll authors were involved in the design of the research. MAVM and KSP performed the research, analysed the data and wrote the manuscript. KJT and KSP revised the manuscript. Competing interestsMAVM has received an independent speaker honorarium from Pfizer. KSP has received research funding from Merck, and advisory board honoraria from Pfizer, Merck and Gilead. Reduced doses of cladribine and cytarabine regimen was effective and well tolerated in patients with refractory-risk multisystem Langerhans cell histiocytosisLangerhans cell histiocytosis (LCH) is a rare disease in which lesions contain cells with features similar to the Langerhans cell of the epidermis. The clinical forms of LCH range from a self-healing unique lesion to multisystem (MS) involvement with risk organ (RO) dysfunction resistant to current therapies. Very young children with MS disease and hepatic or haematological dysfunction are usually treated with multiagent chemotherapy including vinblastine and corticosteroids, but the prognosis of patients with disease progression during this 'standard' chemotherapy is extremely poor (Gadner et al, 2001). Our previous study analysed the poor prognosis of this high-risk group of patients, who presented an overall 3-year survival rate less than 20% (Braier et al, 2010).

Clinical features and treatment of Langerhans cell histiocytosis

“…Six patients received six courses and three received five due to toxic events. Six patients achieved a complete remission after the planned therapy, and the overall probability of survival at 3 years was estimated to be 73%, with much less toxicity than with the higher dose regimen 48 …”

“…However, this regimen is associated with significant toxicity; treatment‐related death was 8%, and profound myelosuppression resulted in high rates of severe infectious complications 46 . Rosso et al have explored a lower dose regimen; in a series of nine patients with refractory multi‐system LCH with risk‐organ involvement, low‐dose cytarabine (100 mg/m 2 /day for 4 days) was combined with cladribine (5 mg/m 2 /day for 5 days) in monthly cycles 48 . Six patients received six courses and three received five due to toxic events.…”

CD207+CD1a+ cells circulate in pediatric patients with active Langerhans cell histiocytosis

“…LCH is characterized by invasive lesions with multiple cell type infiltrations, including pathological CD1a 1 CD207 1 cells affecting one or several organs. [1][2][3][4][5] The etiology of LCH is unknown, and debate centers on LCH resulting from either a malignant transformation of Langerhans cell (LC) precursors or as consequence of a deregulated immune response giving rise to pathological LCs from immature myeloid cells. 2,6,7 LCs are potent antigen-presenting cells of the epidermis that self-renew in the steady state 8 but are recruited in waves after inflammation from the circulation.…”

Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study

“…A literature review identified only one case report in the United States, 19 one survey of 5 cases without risk organs, 19,20 a small survey from China (written in Chinese), 21 and a retrospective survey of 9 cases in Argentina. 22 An important finding in this study involves the DAS (supplemental Table 3). Due to the varied clinical manifestations of LCH, a comprehensive LCH activity scoring system was used to determine the initial severity of the disease and to objectively assess the efficacy of therapy.…”