Haematopoietic stem cell transplantation for refractory Langerhans cell histiocytosis: outcome by intensity of conditioning

Abstract

Summary Patients with Langerhans cell histiocytosis (LCH) refractory to conventional chemotherapy have a poor outcome. There are currently two promising treatment strategies for high-risk patients: the first involves the combination of 2-chlorodeoxyadenosine and cytarbine; the other approach is allogeneic haematopoietic stem cell transplantation (HSCT). Here we evaluated 87 patients with high-risk LCH who were transplanted between 1990–2013. Prior to the year 2000, most patients underwent HSCT following myeloablative conditioning (MAC): only 5 of 20 patients (25%) survived with a high rate (55%) of transplant-related mortality (TRM). After the year 2000 an increasing number of patients underwent HSCT with reduced intensity conditioning (RIC): 49/67 (73%) patients survived, however, the improved survival was not overtly achieved by the introduction of RIC regimens with similar 3-year probability of survival after MAC (77%) and RIC transplantation (71%). There was no significant difference in TRM by conditioning regimen intensity but relapse rates were higher after RIC compared to MAC regimens (28% vs. 8%, p=0.02), although most patients relapsing after RIC transplantation could be salvaged with further chemotherapy. HSCT may be a curative approach in 3 out of 4 patients with high risk LCH refractory to chemotherapy: the optimal choice of HSCT conditioning remains uncertain.

Langerhans cell histiocytosis: therapeutic strategy and outcome in a 30‐year nationwide cohort of 1478 patients under 18 years of age

“…These present survey results confirm, in a multicentric setting, the results of a phase II study (Donadieu et al , ). Before 1998, other second‐line strategies were attempted, such as 2‐CdA monotherapy (Weitzman et al , ) and HSCT with a myeloablative regimen (Akkari et al , ; Kudo et al , ; Veys et al , ). However, none of those attempts improved survival among patients with refractory RO+ LCH (Akkari et al , ; Weitzman et al , ; Kudo et al , ).…”

Histiocytosis – cutaneous manifestations of hematopoietic neoplasm and non‐neoplastic histiocytic proliferations

“…In adults, the frequent adverse effect of a peripheral neuropathy limits its use. Haematopoietic stem cell transplantation has been used as a curative approach in patients with advanced disease . BRAF inhibition is a promising therapeutic target in LHCH.…”

Evaluation and treatment of Langerhans cell histiocytosis patients with central nervous system abnormalities: Current views and new vistas

“…Discoveries of clonality in LCH lesion DC, recurrent mutations in BRAF‐V600E and other MAPK pathway genes, identification of the BRAF‐V600E mutation in hematopoietic stem cells and myeloid precursors in patients with high‐risk LCH, and ability of enforced expression of BRAF‐V600E in myeloid precursors cells to drive a LCH‐like phenotype in mice strongly support LCH as a bona fide myeloproliferative neoplastic disorder . Clinical presentations of LCH vary from single lesions to life‐threatening disseminated disease . Intracranial intraaxial central nervous system (CNS) lesions have been described in LCH patients, especially in those with diabetes insipidus (DI), craniofacial (orbit, mastoid, sphenoid, or temporal bones categorized as “CNS risk”), multisystem disease, and/or with recurrent LCH .…”