Langerhans Cell Histiocytosis, a Rare Disease in Adults: 22 Years of Single Center Experience

Yıl 2022, , 321 - 326, 30.12.2022

Tuba Ersal , Vildan Ozkocaman , Cumali Yalçın , Bedrettin Orhan , Ömer Candar , Sinem Çubukçu , Tuba Güllü Koca , Rıdvan Ali , Fahir Özkalemkaş

https://doi.org/10.32708/uutfd.1165140

Öz

Langerhans cell histiocytosis (LCH) is a rare, multisystemic, and heterogeneous disease seen in adults. There is very little data on how to approach and the treatment of the adult patient. In this study, we retrospectively analyzed 16 adult patients with LCH who were referred to our center between March 2000 and March 2022. 68.7% of the patients were male, and the median age was 30.5 years. At the time of diagnosis, 50% of the patients had a single site, and 50% had multisystemic (MS). Risk organ involvement was present in 3 patients (18.75%). The most involved areas were bone and lung (43.75%), followed by the central nervous system (CNS) (31.25%). All eight patients with indications for systemic treatment were given vinorelbine and steroid treatment in the first line. Other patients underwent surgical excision or radiotherapy. The response rate to treatment was 37.5%, and the partial response rate was 37.5%. 3 (18.75%) of the patients relapsed. All patients with single-site involvement survived and did not relapse. Eleven patients are alive. Median overall survival (OS) was not achieved; 3-year OS was 79.8%. Survival of patients over 30 years of age was found to be lower. However, this difference was not statistically significant (p=0.2). Those with MS had worse median OS data (48 months vs. unavailable, p=0.02). Age at diagnosis over 30 and CNS involvement was associated with lower OS, but this was not statistically significant. Rapid disease progression or refractoriness to treatment was observed in patients with spleen and liver involvement. Especially in patients with poor prognostic features, vinblastine/steroid-based treatments may be insufficient in primary care. Multicenter, prospective studies are needed better to determine the clinical and prognostic features of adult LCH and to develop appropriate treatment strategies.

Anahtar Kelimeler

Adult, langerhans cell histiocytosis, BRAF

Erişkinde Nadir Hastalıklardan Langerhans Hücreli Histiyositoz: 22 Yıllık Tek Merkez Deneyimi

Öz

Langerhans hücreli histiyositoz (LHH) erişkinde nadir rastlanılan multi-sistemik (MS) ve heterojen bir hastalıktır. Erişkin hastaya yaklaşım ve tedaviyle ilgili veri oldukça azdır. Bu çalışmada Mart 2000 ile Mart 2022 tarihleri arasında merkezimize sevk edilen LHH’li 16 erişkin hastayı retrospektif olarak inceledik. Hastaların %68,7’si erkek ve ortanca yaş 30,5 yıl idi. Tanıda hastaların %50’sinde tek bölgede, %50’sinde MS tutulum vardı. Riskli organ tutulumu 3 hastada (%18,75) mevcuttu. En çok tutulan alanlar kemik ve akciğer (%43.75), sonrasında ise santral sinir sistemi (SSS) (%31,25) idi. Sistemik tedavi endikasyonu olan 8 hastanın tamamına birinci sırada vinorelbin ve steroid tedavisi verildi. Diğer hastalara cerrahi eksizyon veya radyoterapi uygulandı. Tedaviye tam yanıt oranı %37.5, kısmi yanıt oranı %37.5 idi. Hastaların 3’ü (%18,75) nüks etti. Tek bölge tutulumu olan hastaların hepsi hayatta ve nüks gelişmedi. On bir hasta ise halen hayattadır. Median genel sağkalıma (OS) ulaşılamadı, 3 yıllık OS %79.8 idi. Otuz yaş üzerindeki hastaların sağkalımı daha düşük bulundu. Ancak bu fark istatistiksel olarak anlamlı değildi (p=0.2). MS hastalığı olanların median OS verileri daha kötüydü (48 aya karşı ulaşılamadı, p=0.02). Tanı yaşının 30’un üzerinde olması ve SSS tutulumu bulunması daha düşük OS ile ilişkiliydi ancak bu istatistiksel olarak anlamlı değildi. Dalak ve karaciğer tutulumu olan hastalarda hızlı hastalık progresyonu ya da tedaviye refrakterlik izlendi. Özellikle kötü prognostik özellikleri olan hastalara birinci basamakta vinblastin/steroid bazlı tedaviler yetersiz kalabilir. Erişkin LHH’da klinik ve prognostik özelliklerinin daha iyi belirlenebilmesi, uygun tedavi stratejilerinin geliştirilmesi için çok merkezli, prospektif çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

Erişkin, langerhans hücreli histiyositoz, BRAF.

Kaynakça

• 1. Lichtenstein L. Histiocytosis X; integration of eosinophilic granuloma of bone, Letterer-Siwe disease, and Schüller-Christian disease as related manifestations of a single nosologic entity. AMA Arch Pathol. 1953;56(1):84-102.
• 2. Allen CE, Merad M, McClain KL. Langerhans-Cell Histiocytosis. The New England journal of medicine. 2018;379(9):856-68.
• 3. Berres ML, Lim KP, Peters T, Price J, Takizawa H, Salmon H, et al. BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups. J Exp Med. 2014;211(4):669-83.
• 4. Allen CE, Li L, Peters TL, Leung HC, Yu A, Man TK, et al. Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells. J Immunol. 2010;184(8):4557-67.
• 5. Luche H, Ardouin L, Teo P, See P, Henri S, Merad M, et al. The earliest intrathymic precursors of CD8α(+) thymic dendritic cells correspond to myeloid-type double-negative 1c cells. Eur J Immunol. 2011;41(8):2165-75.
• 6. Gadner H, Heitger A, Grois N, Gatterer-Menz I, Ladisch S. Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group. Med Pediatr Oncol. 1994;23(2):72-80.
• 7. Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, et al. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008;111(5):2556-62.
• 8. McClain KL. Drug therapy for the treatment of Langerhans cell histiocytosis. Expert Opin Pharmacother. 2005;6(14):2435-41.
• 9. Minkov M, Grois N, Heitger A, Pötschger U, Westermeier T, Gadner H. Response to initial treatment of multisystem Langerhans cell histiocytosis: an important prognostic indicator. Med Pediatr Oncol. 2002;39(6):581-5.
• 10. Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, et al. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001;138(5):728-34.
• 11. Girschikofsky M, Arico M, Castillo D, Chu A, Doberauer C, Fichter J, et al. Management of adult patients with Langerhans cell histiocytosis: recommendations from an expert panel on behalf of Euro-Histio-Net. Orphanet Journal of Rare Diseases. 2013;8(1):72.
• 12. Goyal G, Hu M, Young JR, Vassallo R, Ryu JH, Bennani NN, et al. Adult Langerhans cell histiocytosis: A contemporary single-institution series of 186 patients. Journal of Clinical Oncology. 2019;37(15_suppl):7018-.
• 13. Aricò M, Girschikofsky M, Généreau T, Klersy C, McClain K, Grois N, et al. Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society. Eur J Cancer. 2003;39(16):2341-8.
• 14. Howarth DM, Gilchrist GS, Mullan BP, Wiseman GA, Edmonson JH, Schomberg PJ. Langerhans cell histiocytosis: diagnosis, natural history, management, and outcome. Cancer. 1999;85(10):2278-90.
• 15. Kilpatrick SE, Wenger DE, Gilchrist GS, Shives TC, Wollan PC, Unni KK. Langerhans' cell histiocytosis (histiocytosis X) of bone. A clinicopathologic analysis of 263 pediatric and adult cases. Cancer. 1995;76(12):2471-84.
• 16. Obert J, Vercellino L, Van Der Gucht A, de Margerie-Mellon C, Bugnet E, Chevret S, et al. (18)F-fluorodeoxyglucose positron emission tomography-computed tomography in the management of adult multisystem Langerhans cell histiocytosis. Eur J Nucl Med Mol Imaging. 2017;44(4):598-610.
• 17. Kim HK, Park CJ, Jang S, Cho YU, Park SH, Koh KN, et al. Bone marrow involvement of Langerhans cell histiocytosis: immunohistochemical evaluation of bone marrow for CD1a, Langerin, and S100 expression. Histopathology. 2014;65(6):742-8.
• 18. Goyal G, Tazi A, Go RS, Rech KL, Picarsic JL, Vassallo R, et al. International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults. Blood. 2022;139(17):2601-21.
• 19. Hatemi I, Baysal B, Senturk H, Behzatoglu K, Bozkurt ER, Ozbay G. Adult Langerhans cell histiocytosis and sclerosing cholangitis: a case report and review of the literature. Hepatol Int. 2010;4(3):653-8.
• 20. Cao XX, Li J, Zhao AL, He TH, Gao XM, Cai HC, et al. Methotrexate and cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis: A single arm, single center, prospective phase 2 study. American Journal of Hematology. 2020;95(9).
• 21. Hu M, Goyal G, Young J, Rech K, Bennani NN, Shah MV, et al. Clinical Features and Outcomes of Unifocal Adult Langerhans Cell Histiocytosis. Blood. 2019;134:1667.
• 22. Tazi A, Lorillon G, Haroche J, Neel A, Dominique S, Aouba A, et al. Vinblastine chemotherapy in adult patients with langerhans cell histiocytosis: a multicenter retrospective study. Orphanet J Rare Dis. 2017;12(1):95.
• 23. Cantu MA, Lupo PJ, Bilgi M, Hicks MJ, Allen CE, McClain KL. Optimal therapy for adults with Langerhans cell histiocytosis bone lesions. PLoS One. 2012;7(8):e43257.
• 24. Goyal G, Abeykoon JP, Hu M, Young JR, Shah MV, Bennani NN, et al. Single-agent cladribine as an effective front-line therapy for adults with Langerhans cell histiocytosis. Am J Hematol. 2021;96(5):E146-e50.
• 25. Néel A, Artifoni M, Fontenoy AM, Tessoulin B, Lorillon G, Cohen-Aubart F, et al. Long-term efficacy and safety of 2CdA (cladribine) in extra-pulmonary adult-onset Langerhans cell histiocytosis: analysis of 23 cases from the French Histiocytosis Group and systematic literature review. Br J Haematol. 2020;189(5):869-78.
• 26. Simko SJ, Tran HD, Jones J, Bilgi M, Beaupin LK, Coulter D, et al. Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease. Pediatr Blood Cancer. 2014;61(3):479-87.