Adult Langerhans cell histiocytosis: A contemporary single-institution series of 186 patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7018-7018
Author(s):  
Gaurav Goyal ◽  
Marie Hu ◽  
Jason R Young ◽  
Robert Vassallo ◽  
Jay H Ryu ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Langerhans Cell Histiocytosis ◽  
Overall Response Rate ◽  
Langerhans Cell ◽  
Braf V600e ◽  
First Line ◽  
Multisystem Disease ◽  
Presenting Symptoms ◽  
Systemic Therapies

7018 Background: Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm driven by MAPK-ERK mutations in majority of patients. Contemporary data on treatments and outcomes in adult LCH are lacking. Hence, we undertook this study to analyze a large cohort of adult LCH patients. Methods: This was a retrospective study of adult (≥18 years) LCH patients seen at our institution between 1998 and 2018. Results: We included 186 patients with adult LCH (median age 43; 19-88), and 54% were females. 70% of patients were diagnosed after 2007. Common presenting symptoms were cough/dyspnea (30%), rash (17%), pain/swelling in head (17%), and diabetes insipidus (10%). 70 (38%) patients had multisystem LCH, 62 (33%) had isolated pulmonary LCH, and 35 (19%) had unifocal LCH. Common sites of involvement included lung (59%), bone (37%), skin (21%), and nervous system (16%). 121 (65%) were smokers; 48% of these had lung disease, while 52% had multisystem disease. 18 of 31 tested (58%) patients had BRAF-V600E mutation. Most common first-line treatment was smoking cessation in 24 patients, and led to an overall response rate (ORR) of 83% in pulmonary lesions. Radiation therapy was used in 11 patients, and led to an ORR 82%. Surgical resection of lesion was done in 23 patients, with relapses in 24%. Systemic therapies were used in 78 (42%) patients (Table). Most common first-line systemic therapy was cladribine with ORR of 78%. Vemurafenib was used in 3 patients with BRAF-V600E, leading to an ORR of 67% . After a median follow-up of 23 months (0-261), 21 patients had died. Of these, 10 died of progressive LCH. Median OS was not reached, and mean OS was 196 months. Conclusions: This is the largest contemporary series of adult LCH. It shows that diverse clinical spectrum, ranging from benign course to a progressive multisystem disease. Although smoking cessation was an effective treatment for pulmonary LCH, a large subset required systemic chemotherapy. [Table: see text]

scholarly journals Case Report: Early Association of Vemurafenib to Standard Chemotherapy in Multisystem Langerhans Cell Histiocytosis in a Newborn: Taking a Chance for a Better Outcome?

2021 ◽  
Vol 11 ◽  
Author(s):  
Stefania Gaspari ◽  
Valentina Di Ruscio ◽  
Francesca Stocchi ◽  
Roberto Carta ◽  
Marco Becilli ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Laboratory Data ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Line Treatment ◽  
First Line ◽  
Standard Chemotherapy ◽  
Multisystem Disease ◽  
Response To Chemotherapy ◽  
First Line Treatment

Langerhans cell histiocytosis (LCH) is due to aberrant monoclonal proliferation and accumulation of dendritic cells, ranging from a self-limiting local condition to a rapidly progressive multisystem disease with poor prognosis. Pathogenic cells originate from a myeloid-derived precursor characterized by an activation of the MAPK/ERK signaling pathway in about 70% of cases. In particular, BRAF V600E mutation is usually associated with a more severe clinical course and poor response to chemotherapy. We report on a newborn with multisystem LCH in life-threatening medical conditions. At diagnosis, the patient was successfully treated with the early association of BRAF inhibitor Vemurafenib to standard chemotherapy representing a new approach in first-line treatment. A rapid clinical improvement with a prompt fever regression from day 2 and complete resolution of skin lesions by week 2 were observed; laboratory data normalized as well. Vemurafenib was discontinued after 12 months of treatment. No signs of relapse occurred after 12 months of discontinuation. This case indicates that early combination of target therapy with standard treatment may induce rapid response and prolonged disease remission without significant toxicities in infants. This approach represents a valid and safe option as first-line treatment in multisystem disease, especially in high-risk patients.

Cladribine Activity in Adult Langerhans-Cell Histiocytosis

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4125-4130 ◽  
Author(s):  
Alan Saven ◽  
Carol Burian
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Overall Response Rate ◽  
Single Agent ◽  
Langerhans Cell ◽  
Median Response ◽  
Major Activity ◽  
Prior Surgery ◽  
Grade 3 ◽  
Experienced Grade

Abstract Langerhans-cell histiocytosis (LCH) results from the accumulation of tissue histiocytes derived from the same progenitor cells as monocytes. Because cladribine is potently toxic to monocytes, we conducted a phase II trial of cladribine. Cladribine was administered to 13 LCH patients at 0.14 mg/kg per day by 2-hour intravenous infusion for 5 consecutive days, every 4 weeks for a maximum of six courses. Median age was 42 years (range, 19 to 72) and median pretreatment disease duration was 99 months (range, 6 to 252). One patient was untreated, one had received prior prednisone only, one prior radiation only, six prior radiation and chemotherapy, and four prior surgery, radiation, and chemotherapy. Seven patients had cutaneous involvement, six multifocal osseous, six pulmonary, two each with soft tissue and nodal involvement, and four had diabetes insipidus. Of 13 patients, 12 were evaluable for response and all for toxicity. After a median of three courses (range, 1 to 6), seven (58%) patients achieved complete responses (two pathologic and five clinical) and two (17%) patients achieved partial responses; overall response rate, 75%. Median response follow-up duration was 33 months (range, 1 to 65). Seven patients experienced grade 3 to 4 neutropenia. Only one patient had a documented infection, dermatomal herpes zoster. At a median follow-up of 42 months (range, 5 to 76), 12 patients remain alive and one patient has died. Thus, cladribine has major activity in adult LCH and warrants further investigation in both pediatric and adult LCH as a single agent and in combination with other drugs.

Upper Gastrointestinal Langerhans Cell Histiocytosis: A Report of 2 Adult Cases and a Literature Review

2020 ◽  
pp. 106689692096456
Author(s):  
Yui Matsuoka ◽  
Yoshiki Iemura ◽  
Masakazu Fujimoto ◽  
Shinsuke Shibuya ◽  
Atsushi Yamada ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Mononuclear Cells ◽  
Malignant Neoplasm ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Gi Tract ◽  
Upper Gi ◽  
Upper Gastrointestinal ◽  
Upper Gi Tract

Langerhans cell histiocytosis (LCH) with primary involvement of the upper gastrointestinal (GI) tract is rare. We report 2 adult cases of localized LCH in the upper-GI tract, including the second reported adult case of esophageal LCH and review 11 previously reported cases. Case 1 involved the esophagus of a 61-year-old man; histiocytosis was detected when endoscopy was performed for an examination of epigastric pain. Case 2 involved the stomach of a 56-year-old woman wherein the lesion was detected during a follow-up endoscopy after Helicobacter pylori infection. Both biopsy specimens exhibited diffuse proliferation of mononuclear cells with nuclear convolution and a background of eosinophilic infiltrate. The cells were immunohistochemically positive for CD1a and langerin, and BRAF V600E mutation was detected in Case 2. Follow-up endoscopy for both cases revealed that the lesions disappeared without any treatment. It is important to avoid misdiagnosing LCH of the upper-GI tract as a malignant neoplasm.

scholarly journals Pulmonary Langerhans Cell Histiocytosis: An Update From the Pathologists' Perspective

2016 ◽  
Vol 140 (3) ◽  
pp. 230-240 ◽  
Author(s):  
Anja C. Roden ◽  
Eunhee S. Yi
Keyword(s):  
Pulmonary Hypertension ◽  
Langerhans Cell Histiocytosis ◽  
Treatment Options ◽  
Additional Treatment ◽  
Langerhans Cell ◽  
Braf V600e ◽  
First Line ◽  
Clonal Proliferation ◽  
Pulmonary Langerhans Cell Histiocytosis ◽  
Appropriate Treatment

Context Pulmonary Langerhans cell histiocytosis (PLCH) is a rare histiocytic disorder that almost exclusively affects the lungs of smokers. PLCH is characterized by bronchiolocentric nodules and/or cysts in an upper and mid lung distribution with sparing of the costophrenic angles. The diagnosis can be challenging and often requires transbronchial biopsy or surgical lung biopsy. Pulmonary hypertension is a relatively common and sometimes severe complication of PLCH. The pathogenesis of PLCH is still debated. Recently, BRAF V600E mutation and BRAF expression have been identified in some patients with PLCH, suggesting that at least a subset of PLCH has a clonal proliferation. While smoking cessation is the first-line treatment of PLCH, some patients might require additional treatment and eventually transplant. Given that the lesional cells of PLCH express BRAF in some patients, MAPKinase pathway–targeted treatment might be useful for therapy-resistant patients. Objective —To present the more recently recognized clinical and pathologic aspects of PLCH, including pulmonary hypertension in PLCH, pathogenesis, and treatment, as well as the basic diagnostic approach to PLCH. Data Sources Authors' own research, and search of literature database (PubMed) and UpToDate. Conclusions —Despite the recent progress, more studies are needed to elucidate the biology of PLCH for identification of prognostic factors and appropriate treatment options, especially for therapy-refractory PLCH cases.

Cladribine Activity in Adult Langerhans-Cell Histiocytosis

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4125-4130 ◽  
Author(s):  
Alan Saven ◽  
Carol Burian
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Overall Response Rate ◽  
Single Agent ◽  
Langerhans Cell ◽  
Median Response ◽  
Major Activity ◽  
Prior Surgery ◽  
Grade 3 ◽  
Experienced Grade

Langerhans-cell histiocytosis (LCH) results from the accumulation of tissue histiocytes derived from the same progenitor cells as monocytes. Because cladribine is potently toxic to monocytes, we conducted a phase II trial of cladribine. Cladribine was administered to 13 LCH patients at 0.14 mg/kg per day by 2-hour intravenous infusion for 5 consecutive days, every 4 weeks for a maximum of six courses. Median age was 42 years (range, 19 to 72) and median pretreatment disease duration was 99 months (range, 6 to 252). One patient was untreated, one had received prior prednisone only, one prior radiation only, six prior radiation and chemotherapy, and four prior surgery, radiation, and chemotherapy. Seven patients had cutaneous involvement, six multifocal osseous, six pulmonary, two each with soft tissue and nodal involvement, and four had diabetes insipidus. Of 13 patients, 12 were evaluable for response and all for toxicity. After a median of three courses (range, 1 to 6), seven (58%) patients achieved complete responses (two pathologic and five clinical) and two (17%) patients achieved partial responses; overall response rate, 75%. Median response follow-up duration was 33 months (range, 1 to 65). Seven patients experienced grade 3 to 4 neutropenia. Only one patient had a documented infection, dermatomal herpes zoster. At a median follow-up of 42 months (range, 5 to 76), 12 patients remain alive and one patient has died. Thus, cladribine has major activity in adult LCH and warrants further investigation in both pediatric and adult LCH as a single agent and in combination with other drugs.

BRAF V600E Mutation: A Significant Biomarker for Prediction of Disease Relapse in Pediatric Langerhans Cell Histiocytosis

2019 ◽  
Vol 22 (5) ◽  
pp. 449-455 ◽  
Author(s):  
Erdener Ozer ◽  
Akin Sevinc ◽  
Dilek Ince ◽  
Resmiye Yuzuguldu ◽  
Nur Olgun
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Direct Sequencing ◽  
Prognostic Significance ◽  
Braf V600e Mutation ◽  
Langerhans Cell ◽  
Braf V600e ◽  
Erk Pathway ◽  
Disease Relapse ◽  
Multisystem Disease ◽  
Mutational Status

Langerhans cell histiocytosis (LCH) is a rare disease presenting with usually a localized disease but sometimes a widespread aggressive disorder especially in children. Among the somatic mutations in RAF-MEK-ERK pathway, especially BRAF mutation has been detected so far in LCH. We aimed in this study to investigate the prognostic significance of the mutations of target genes playing a role in the RAF-MEK-ERK pathway in pediatric LCH. Mutation analyses were performed on tumor DNA extracted from formalin-fixed paraffin-embedded biopsy specimens of 38 pediatric LCH cases using a direct sequencing technique for BRAF, ARAF, MAP2K1, and MAP3K1 genes. The mutational status was correlated statistically with survival, clinical progression (disease relapse), and the established clinical prognostic parameters of LCH such as age, gender, localization, multisystem disease, central nervous system risk lesions, and risk organ or special-site involvement. BRAF V600E mutation was detected in 14 cases (36.8%), whereas ARAF mutation was found in only 1 case. No mutations were identified for MAP2K1 and MAP3K1 genes. The association of BRAF V600E mutation was significant in children with multisystem disease, younger age (<2 years), skin, and special organ involvement. BRAF V600E mutation was an independent predictive parameter for disease relapse. We therefore conclude that BRAF V600E mutation may be a significant marker for predicting disease progression in LCH and a candidate for targeted therapy for children with disease relapse and multisystem disease.

scholarly journals A confusing case report of pulmonary langerhans cell histiocytosis and literature review

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 178-182
Author(s):  
Yang Li ◽  
Wang Zhen ◽  
Ulrich Costable ◽  
Xu Jun ◽  
Ren Zhe ◽  
...  
Keyword(s):  
Smoking Cessation ◽  
Case Report ◽  
Literature Review ◽  
Rare Disease ◽  
Langerhans Cell Histiocytosis ◽  
Langerhans Cell ◽  
First Line ◽  
Therapy Options ◽  
Pulmonary Langerhans Cell Histiocytosis ◽  
Insidious Onset

AbstractPulmonary Langerhans Cell Histiocytosis (PLCH) is a rare disease. From the insidious onset and nonspecific manifestations, it is difficult to diagnose PLCH. To help improve the diagnosis and therapy options of adult PLCH, we present this case report and literature review about a confusing case of PLCH. In this report, we present a 37-year-old male PLCH case that was negative for CD1a and S100 expression. Smoking cessation and use of prescribed Spiriva appeared to improve the patient’s symptoms. To the best of our knowledge, this is the first reported case of PLCH in which improved symptoms were seen with the use of Spiriva alone.The mechanism is not clear, but potentially has some relationship with dilating the airway, decreasing the mucous hypersecretion and promoting anti-inflammatory pathways. From this patient’s case, we may be able to find more cases to then find other first line therapies for PLCH patients.

scholarly journals Specific Guidelines Including Multidisciplinary Approach Is Critical of Management of Langerhans Cell Histiocytosis in Adults

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1041-1041
Author(s):  
Lorenzo Rizzo ◽  
Michelina Santopietro ◽  
Gianluca Sfaciotti ◽  
Marco Brunori ◽  
Luisa Cardarelli ◽  
...  
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Multidisciplinary Approach ◽  
Central Nervous System Involvement ◽  
Langerhans Cell ◽  
Age At Diagnosis ◽  
Braf V600e ◽  
Adequate Treatment ◽  
Previously Treated ◽  
Over Time

The knowledge of Langerhans Cell Histiocytosis (LCH) is based on pediatric studies. Adults with LCH are usually treated with pediatric protocols. In 2001, guidelines for adults with LCH (GIMEMA LCH 2001) were proposed, in order to standardize the diagnostic and therapeutic approaches for this category of patients. The aims of this retrospective study are: a) to evaluate the role of a multidisciplinary assessment in adults with LCH, according to the GIMEMA LCH 2001 guidelines, and b) to analyze the results obtained with the GIMEMA LCH 2001 guidelines and those obtained with pediatric protocols. Pts aged >18 years with a diagnosis of LCH (S-100+, CD1a+, CD207+) managed at our Institution since 1985 to 2018 were considered. As diagnostic and treatment approaches, two different strategies were used over time: the GIMEMA LCH 2001 guidelines and the pediatric protocols. The GIMEMA LCH 2001 guidelines included a multidisciplinary diagnostic work-up with complete odontostomatologic, pulmonary and endocrinologic assessments; treatment strategy consisted of: wait and see or local therapy in unifocal single system (SS), indomethacin in bone multifocal SS and vinblastine combined with low-dose prednisone (PDN) in multi-system (MS), PDN in pulmonary honey-combing disease (PHCD) and cladribine in central nervous system involvement. DAL-HX 83 and 90, LCH-I and LCH II were the pediatric protocols utilized over time. Response to treatment was defined as complete (CR) or intermediate (IR). Persistence of the symptoms and/or appearance of new lesions were defined no response (NR). Progression was considered the appearance of symptoms and/or new lesions after initial response. One-hundred-thirty-one LCH pts (females 72, males 59) with a median age at diagnosis of 36 years (range 18 - 71) were considered. Median follow up was 43 months (range 12 - 330). One-hundred-seven patients were managed according to the GIMEMA LCH 2001 guidelines, 16 of them previously treated with a pediatric protocol. Pulmonary and/or oral involvements were identified in 31/107 (29%) and 12/107 (11%) patients, respectively, 5/16 (31%) and 3/16 (19%), respectively, of previously treated asymptomatic patients. Ninety-one newly diagnosed patients (median age at diagnosis: 36 years) were treated according to the GIMEMA LCH 2001 guidelines and 40 (median age at diagnosis: 33 years) were managed with pediatric protocols. All patients treated with the GIMEMA LCH 2001 were evaluable for response. In particular, all patients with SS-LCH achieved a response (100%), that was complete in 20/26 (76.9%) unifocal-SS and in 10/14 (71.4%) multifocal-SS. All but one patient with MS-LCH reached a response that was complete in 22/45 (48.9%). Of 6 pts with PHCD, 5 had a IR and one a CR. No pt presented CNS involvement at initial diagnosis. Thirty-nine of 40 pts managed with pediatric protocols were evaluable for response. All 13 pts with SS-LCH had a response that was complete in 6 (46.1%). Among 26 patients with MS-LCH, 3 of them with organ risk involvement achieved a response, that was complete in 1, while among 23 patients without organ risk, 12 (52.2%), 8 (34.8%) and 3 (13%) had a CR, IR and NR, respectively. Overall, 12 patients were lost to follow-up. Disease progression was recorded in 47/95 pts (49.5%) after a median time of 19 months (range: 6-147 months). The progression-free survival at 43 months was significantly better for patients treated according to the GIMEMA LCH 2001 guidelines compared to those managed with pediatric protocols, 67% (IC95% 53.14 - 80.86%) vs 48% (IC95% 31.37 - 64.63%), respectively (p 0.005). Overall, 7 deaths were recorded, 5 in patients treated with the pediatric protocols. The overall survival at 43 months, was similar in patients managed with the GIMEMA LCH 2001 guidelines and in those treated with pediatric protocols (97.9%, CI 95%: 93.75% - 100% and 97.3%, (IC95% 91.96% - 100%). BRAF V600E mutation was found in 13/35 (37%) evaluable cases. No differences in response and outcome between BRAFV600E-mutated patients and those not-mutated were found. Our experience in a large cohort of LCH adults shows that a multidisciplinary approach is useful in identifying organ involvement in adults, including those asymptomatic. This is critical for an adequate treatment. Moreover, guidelines specific for adults with LCH proved efficacy in improving the outcome in this category of patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical characteristics and survival of children with Langerhans cell hystiocytosis

2008 ◽  
Vol 136 (9-10) ◽  
pp. 514-518
Author(s):  
Nada Krstovski ◽  
Dragana Janic ◽  
Lidija Dokmanovic ◽  
Radivoj Brdar
Keyword(s):  
Langerhans Cell Histiocytosis ◽  
Clinical Characteristics ◽  
Clinical Presentation ◽  
Clinical Course ◽  
Langerhans Cell ◽  
Single System ◽  
Multisystem Disease ◽  
System Disease ◽  
The Central Nervous System

INTRODUCTION Langerhans cell histiocytosis is a rare disease in children, initial presentation is variable, clinical course, prognosis and survival are mostly unpredictable. OBJECTIVE To summarise clinical characteristics and treatment results in children with Langerhans cell histiocytosis. METHOD Retrospectively there were analyzed patients with LCH diagnosed and treated at Hematology Department of University Children's Hospital in Belgrade from 1990 to 2006. Clinical presentation, therapy and survival according to Kaplan-Meier's statistical test was analysed. RESULTS 30 patients were treated, aged from 4 months to 14 years, mean 3.9 years, median 2.3 years, 18 (60%) males, 12 (40%) females. A single system disease was diagnosed in 16 (53%) patients, of whom 6 patients with multifocal bone disease. All patients were in complete remission averagely following162 and 82 months respectively. Multisystem disease was found in 14 (47%) patients. The lymph nodes and skin were more frequently involved organs than the central nervous system (diabetes insipidus), lung, liver and spleen. The number of involved organs ranged from 2 to 8, mean 4.2. Four patients died due to disease progression 3, 16, 36 and 66 months after diagnosis. Nine patents with multisystem disease were in remission with 117 months of follow-up. One patient was lost on follow-up. CONCLUSION The clinical course of patients with a single system disease is usually benign while a multisystem disease has to be aggressively treated with precise initial evaluation and staging before therapy.

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