Deepak Chellapandian1,2,3, Melissa R Hines4, Rui Zhang5, Michael Jeng6, Cor van den Bos7, Vicente Santa-María López8, Kai Lehmberg9, Elena Sieni10, Yini Wang11, Taizo Nakano12, James A Williams13, Nicholas J Fustino14, Itziar Astigarraga15, Ira J Dunkel16, Oussama Abla1, Astrid G S van Halteren17, Deqing Pei18, Cheng Cheng18, Sheila Weitzman1, Lillian Sung1, Kim E Nichols3. 1. Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada. 2. Blood and Marrow Transplant Program, Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida. 3. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. 4. Division of Critical Care, Department of Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee. 5. Hematology and Oncology Center, Beijing Children's Hospital, Beijing, China. 6. Division of Pediatric Hematology/Oncology, Lucile Packard Children's Hospital Stanford, Palo Alto, California. 7. Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, Amsterdam, The Netherlands. 8. Department of Pediatric Hematology/Oncology, Sant Joan de Deu Hospital, Barcelona, Spain. 9. Department of Paediatric Haematology/Oncology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. 10. Department of Paediatric Haematology/Oncology, Meyer Children's University Hospital, Florence, Italy. 11. Department of Medical Oncology, Beijing Friendship Hospital, Beijing, China. 12. Pediatric Hematology/Oncology, Children's Hospital Colorado, University of Colorado School of Medicine, Denver, Colorado. 13. Division of Pediatric Hematology/Oncology, Phoenix Children's Hospital, Phoenix, Arizona. 14. Pediatric Hematology/Oncology, Blank Children's Hospital, Des Moines, Iowa. 15. Department of Paediatric Haematology/Oncology, BioCruces Health Research Institute, Cruces University Hospital, Bizkaia, Spain. 16. Pediatric Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. 17. Immunology Laboratory, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands. 18. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
Abstract
BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a-positive (CD1a+ )/CD207+ histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Nevertheless, to the authors' knowledge, little is known regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop HLH within the context of MS-LCH (hereafter referred to LCH-associated HLH). METHODS: To gain further insights, the authors conducted a retrospective, multicenter study and collected data regarding all patients diagnosed with MS-LCH between 2000 and 2015. RESULTS: Of 384 patients with MS-LCH, 32 were reported by their primary providers to have met the diagnostic criteria for HLH, yielding an estimated 2-year cumulative incidence of 9.3% ± 1.6%. The majority of patients developed HLH at or after the diagnosis of MS-LCH, and nearly one-third (31%) had evidence of an intercurrent infection. Patient age <2 years at the time of diagnosis of LCH; female sex; LCH involvement of the liver, spleen, and hematopoietic system; and a lack of bone involvement each were found to be independently associated with an increased risk of LCH-associated HLH. Patients with MS-LCH who met the criteria for HLH had significantly poorer 5-year survival compared with patients with MS-LCH who did not meet the criteria for HLH (69% vs 97%; P < .0001). CONCLUSIONS: Given its inferior prognosis, further efforts are warranted to enhance the recognition and optimize the treatment of patients with LCH-associated HLH.
BACKGROUND:Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a-positive (CD1a+ )/CD207+ histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Nevertheless, to the authors' knowledge, little is known regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop HLH within the context of MS-LCH (hereafter referred to LCH-associated HLH). METHODS: To gain further insights, the authors conducted a retrospective, multicenter study and collected data regarding all patients diagnosed with MS-LCH between 2000 and 2015. RESULTS: Of 384 patients with MS-LCH, 32 were reported by their primary providers to have met the diagnostic criteria for HLH, yielding an estimated 2-year cumulative incidence of 9.3% ± 1.6%. The majority of patients developed HLH at or after the diagnosis of MS-LCH, and nearly one-third (31%) had evidence of an intercurrent infection. Patient age <2 years at the time of diagnosis of LCH; female sex; LCH involvement of the liver, spleen, and hematopoietic system; and a lack of bone involvement each were found to be independently associated with an increased risk of LCH-associated HLH. Patients with MS-LCH who met the criteria for HLH had significantly poorer 5-year survival compared with patients with MS-LCH who did not meet the criteria for HLH (69% vs 97%; P < .0001). CONCLUSIONS: Given its inferior prognosis, further efforts are warranted to enhance the recognition and optimize the treatment of patients with LCH-associated HLH.
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