Targeted inhibition of the MAPK pathway: emerging salvage option for progressive life-threatening multisystem LCH by Alexandra Kolenová, Raphaela Schwentner,

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Targeted inhibition of the MAPK pathway: emerging salvage option for progressive life-threatening multisystem LCH by Alexandra Kolenová, Raphaela Schwentner, Gunhild Jug, Ingrid Simonitsch-Klupp, Christoph Kornauth, Lukáš Plank, Júlia Horáková, Ivana Bodová, Tomáš Sýkora, Lucia Geczová, Wolfgang Holter, Milen Minkov, and Caroline Hutter BloodAdv Volume 1(6):352-356 February 14, 2017 © 2017 by The American Society of Hematology

Effect of vemurafenib on disease and BRAF V600E levels. Effect of vemurafenib on disease and BRAF V600E levels. (A) Percentage of the BRAF V600E allele in the peripheral blood of patients at time of relapse (patient 107) or diagnosis (5 other patients). Patient 107 is the patient described in this case report; patients 113 and 134 had MS-LCH, patients 103 and 216 had multifocal bone LCH, and peripheral blood of patient 151 was used as a negative control (no BRAF V600E mutation in lesional cells). (B) Immunohistochemistry of a biopsy (gingiva) of patient 107 with an antibody against V600E. Original magnification ×40. (C) Monitoring of laboratory parameters under vemurafenib. (D) Vemurafenib dosage (milligrams per day) administered to the patient. (E) Disease activity score (DAS) during treatment with vemurafenib until HSCT (see also supplemental Table 1). (F) Percentage of circulating BRAF V600E alleles in the peripheral blood (whole blood) during therapy. Alexandra Kolenová et al. Blood Adv 2017;1:352-356 © 2017 by The American Society of Hematology

Effect of vemurafenib on skin lesions and bone marrow. Effect of vemurafenib on skin lesions and bone marrow. Skin lesions at start of therapy with vemurafenib (A) and after 10 months of treatment with vemurafenib (B). Bone marrow biopsy stained with an antibody against CD1a before (C) and after 9 months (D) of treatment with vemurafenib. Expression of the mutated BRAF protein in the bone marrow before (E) and after 9 months (F) of treatment with vemurafenib. Original magnifications ×20 (C-D) and ×40 (E-F). Alexandra Kolenová et al. Blood Adv 2017;1:352-356 © 2017 by The American Society of Hematology