Langerhans cell histiocytosis with central nervous system involvement—complete response to 2‐chlorodeoxyadenosine after failure of tyrosine kinase inhibitor therapies with sorafenib and imatinib

Abstract

Langerhans cell histiocytosis (LCH) is rare in adults, and only a subset of these patients suffers from central nervous system (CNS) involvement. Hence, evidence-based treatment recommendations are lacking. A case of a 20-year-old student with multisystem LCH and extensive CNS involvement is described, who showed a durable response to 2-chlorodeoxyadenosine after prior therapies with the tyrosine kinase inhibitors sorafenib and imatinib. In accordance to the experiences provided by other case series, which are reviewed herein, 2-chlorodeoxyadenosine can be considered an effective and safe option for adult LCH with CNS involvement.

Long‐term efficacy and safety of 2CdA (cladribine) in extra‐pulmonary adult‐onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review

“…General characteristics. We retrieved 19 publications (five case series and 14 isolated case reports) including 48 patients (Betticher et al , 1994; Dimopoulos et al , 1997; Conias et al , 1998; Saven & Burian, 1999; Weitzman et al , 1999; Grau et al , 2001; Chang et al , 2002; Pardanani et al , 2003; Goh et al , 2003; Ghia et al , 2004; Sander et al , 2004; Caputo et al , 2005; Braiteh & Kurzrock, 2006; Mottl et al , 2006; Dhall et al , 2008; Aerni et al , 2008; Lazor et al , 2009; Black et al , 2011; Baumann et al , 2012). The baseline characteristics of the patients are reported in Table SI.…”

Langerhans cell histiocytosis in children – a disease with many faces. Recent advances in pathogenesis, diagnostic examinations and treatment

“…Moreover, retinoic acid [ 97 ], thalidomide and its analogues [ 98 – 100 ], as well as high doses of steroids [ 55 , 100 ], have been proposed for the treatment of ND-CNS-LCH. Cytotoxic-immunosuppressive approaches have included cladribine [ 101 , 102 ] and cytarabine because of good CNS penetration [ 9 , 17 , 56 ].…”

Cladribine treatment for Erdheim–Chester disease involving the central nervous system and concomitant polycythemia vera: A case report

“…Although there has been no previous report of a patient with ECD exhibiting PV at diagnosis, we treated a patient diagnosed with the very rare concomitant development of ECD harboring the BRAF V600E mutation with CNS involvement, and PV with the JAK2 V617F mutation. Based on previous case reports, we started cladribine therapy 11 , 17 . This case confirmed cladribine to be an effective therapy for ECD harboring the BRAF V600E mutation with CNS involvement.…”

“…However, CNS involvement is reported to be a poor prognostic factor when treating ECD with IFNα due to the blood–brain barrie 10 . On the other hand, therapy with 2-chlorodeoxyadenosine (cladribine), a purine analog, was reported to be effective for LCH harboring the BRAF V600E mutation with CNS involvement 11 …”