Autologous hematopoietic stem cell transplantation for efficient treatment of multisystem, high-risk, BRAF V600E-negative Langerhans cell histiocytosis

Abstract

Langerhans cell histiocytosis (LCH) is a disorder caused by clonal proliferation of CD1a+/CD207+ cells and characterized by varying degrees of organ involvement. Treatment of LCH is risk adapted; patients with multisystem disease and risk-organ involvement require more intensive therapy. Optimal therapies for multisystem, high-risk LCH remain uncertain. Recently, targeted therapy using inhibitors of mutated BRAF (the gene encoding serine/threonine-protein kinase B-Raf) has proven very effective in patients with multisystem refractory LCH. Herein, we report a case of LCH with involvement of the bones, liver, and lymph nodes. Using next-generation sequencing of the patient’s pathological sample, we identified a mutation in MAP2K1 in exon 3 (c.362G>C, p.Cys121Ser) and no mutation in BRAF; thus, high-risk, multisystem LCH with MAP2K1 mutation and wild-type BRAF was diagnosed. After four chemotherapy treatments (COEP regimen), the patient received autologous hematopoietic stem cell transplantation (auto-HSCT). Complete remission was confirmed by follow-up positron emission tomography–computed tomography, which showed no lesions in liver, lymph nodes, or bones compared with the pretreatment period. To date, the patient has sustained good health for 24 months. In conclusion, auto-HSCT may be an effective treatment option for high-risk, multisystem BRAF V600E-negative LCH.

International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults

“… 109 There are 6 published cases of adults with refractory LCH (age range 21-35 years) who underwent HSCT, with most cases achieving sustained remissions. 136 , 137 , 138 , 139 , 140 , 141 Data on the efficacy of BRAF and MEK inhibitors in frontline and relapsed setting are emerging with several published cases. The majority had BRAF- V600E mutation and received vemurafenib, although there are also reports using cobimetinib, trametinib, and dabrafenib + trametinib.…”

Langerhans cell histiocytosis: unusual bone marrow infiltration—report of 2 cases in Ecuador

“…Due to the more aggressive clinical presentation and poor prognosis associated with bone marrow involvement, the patients in this report were treated with systemic chemotherapy (cyclosporine for the patient 1 and vinblastine + methotrexate for the patient 2) and steroids. Although the criteria for bone marrow transplantation are not fully established, it is indicated as a last resort after the failure of chemotherapy in these patients ( 15 ), a course of action proposed for patient 1 in this report.…”

Management der Langerhans-Zell-Histiozytose bei erwachsenen Patienten

“…Bei Erwachsenen mit sehr seltenen lebensbedrohlich aggressiven Verläufen einer LCH kommen eine autologe [28] oder allogene Stammzelltransplantation [29] in Betracht. Bei Kindern mit Hochrisiko-LCH stellt eine allogene hämatopoetische Stammzelltransplantation ein inzwischen etabliertes Therapieprinzip dar mit Heilung von 75 % der Patienten [30].…”