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.

Keywords: BRAF V600E mutation negative; Langerhans cell histiocytosis; MAP2K1 mutation; autologous hematopoietic stem cell transplantation; high-risk; multisystem.

Figure 1.

The biopsy of the lesions around the L2 vertebral body showing a large number of Langerhans cells with eosinophilic granulocytes and small lymphocytes. (A) hematoxylin and eosin (HE); (B) CD207++; (C) CD1a+; (D) S100++. ×200.

Figure 2.

The PET-CT images of a 28-year-old male patient with LCH before (1 April 2016) and after (1 January 2017) receiving auto-HSCT. (A–D) Images showing multiple lesions (arrowheads in A and C) in liver, lymph nodes, and bones, as well as osteolytic lesions (T7, T8, T9, and S1) with SUVmax 10.5 before therapy. (a–d) Images showing no highly FDG-avid lesions in liver, lymph nodes, or bones and smaller osteolytic lesions. Compared with the initial diagnosis, we found evidence of peripheral sclerosis (T7, T8, T9, and S1), an indicator of bone regeneration. PET-CT, positron emission tomography–computed tomography; LCH, Langerhans cell histiocytosis; auto-HSCT, autologous hematopoietic stem cell transplantation; SUVmax, maximum standardized uptake value; FDG, 18F-fluorodeoxyglucose.

Figure 3.

The liver PET-CT scan showing significantly decreased FDG signal after the administration of auto-HSCT (e; 1 January 2017) compared with the pretreatment period (E; 1 April 2016). PET-CT, positron emission tomography–computed tomography; FDG, 18F-fluorodeoxyglucose; auto-HSCT, autologous hematopoietic stem cell transplantation.

Figure 4.

Metabolic changes in retroperitoneal lymph nodes at the initial diagnosis (1 April 2016) and after auto-HSCT (1 January 2017). (F) Multiple FDG-avid lesions in retroperitoneal lymph nodes (arrowheads). (f) No FDG-avid lesions in retroperitoneal lymph nodes. Auto-HSCT, autologous hematopoietic stem cell transplantation; FDG, 18F-fluorodeoxyglucose.