Childhood Langerhans cell histiocytosis hematological involvement: severity associated with BRAFV600E loads.

Autor:	Thalhammer J; Institute of Hematology and Pediatric Oncology,Centre Leon Berard,Lyon, France., Jeziorski E; University Hospital of Montpellier, Montpellier, France., Marec-Berard P; Institut d'Hématologie et Oncologie Pédiatrique (IHOPe)., Barkaoui MA; French Reference Center for Langerhans Cell Histiocytosis, Trousseau Hospital, Paris, France., Pagnier A; Centre Hospitalo-Universitaire de Grenoble, Grenoble Cedex 9, France., Rohrlich PS; CHU Nice, Nice, France., Chevallier A; Hopital Trousseau, Paris, France., Carausu L; CHRU Brest, Brest, France., Aladjidi N; Bordeaux University Hospital / CEREVANCE, BORDEAUX, France., Rigaud C; Gustave Roussy Cancer Campus, Villejuif, France., Leruste A; Institut Curie, Paris, France., Azarnoush S; Hôpital Robert Debré, AP-HP, Université de Paris, Paris, France, Paris, France., Lauvray T; Centre Hospitalo-Universitaire de Limoges, Limoges, France., Le Louet S; French Reference Center for Langerhans Cell Histiocytosis, Paris, France., Gandemer V; Department of Pediatric Hematology and Oncology CHU Hopital Sud, Rennes, France., Treguier P; Department of Pediatric Hematology and Oncology CHU Hopital Sud, Rennes, France., Mansuy L; Centre Hospitalo-Universitaire de Nancy, NANCY, France., Pasquet M; Hopital Purpan, CHU Toulouse, Toulouse, France., Olivier L; Hopital Purpan, CHU Toulouse, Toulouse, France., Rome A; La Timone University Hospital of Marseille, APHM, Marseille, France., Saultier P; La Timone University Hospital of Marseille, APHM, Department of Pediatric Oncology, Marseille, France., Isfan F; La Timone University Hospital of Marseille, APHM, Department of Pediatric Oncology, Marseille, France., Renard C; Institut d'hématologie et d'oncologie pédiatrique, Hospices Civils de Lyon, LYON, France., Li Thiao Te V; CHU AMIENS, Amiens, France., Salmon A; CHRU STRASBOURG, STRASBOURG, France., Blanc L; Centre Hospitalier Universitaire de Poitiers, Poitiers, France., Abou Chahla W; CHU de Lille, Hopital Jeanne De Flandre, Lille, France., Lambilliotte A; CHRU de Lille France, Lille, France., Stephan JL; University of Saint Etienne, Saint Etienne, France., Geissmann F; Memorial Sloan Kettering Cancer Center, NY, New York, United States., Lejeune J; Tours university hospital, Tours, France., Mallebranche C; Université d'Angers, Université de Nantes, Inserm, CNRS, CRCI2NA, SFR ICAT, Angers, France; CHU Angers, Pediatric immuno-hemato-oncology Unit, Angers, France, Angers, France., Reguerre Y; HOPITAL FELIX GUYON LA REUNION, saint denis, France., Grain A; Nantes University Hospital, Nantes, France., Thomas C; Nantes University Hospital, Nantes, France., Hélias-Rodzewicz Z; Nantes University Hospital, Nantes, France., Moshous D; Hôpital Necker-Enfants Malades, Paris, France., Fenneteau O; Hôpital Robert Debré APHP, PARIS, France., Coulomb-L'hermine A; Sorbonne Université - Trousseau Hospital, Paris, France., Lapillonne H; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, AP-HP Hôpital Trousseau, Paris, France, France., de Saint Basile G; Hopital Necker-Enfants Malades, Paris, France., Emile JF; Paris-Saclay University, Versailles SQY University, EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (AP-HP), Ambroise-Paré Hospital, Smart Imaging, Service de Pathologie, Boulogne, France., Héritier S; French Reference Center for Langerhans Cell Histiocytosis, PARIS, France., Donadieu J; Hopital Trousseau, Paris, France.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Nov 01. Date of Electronic Publication: 2024 Nov 01.
DOI:	10.1182/blood.2024025625
Abstrakt:	Hematological involvement (HI) is one of the life-threatening risk organs (ROs) in Langerhans cell histiocytosis (LCH). Lahey criteria have defined HI since 1975 as hemoglobin <10 g/dL and/or platelets <100 G/L and/or leukopenia (white blood cell count <4 G/L) and/or neutrophils <1.5 G/. Among the 2313 patients <18 years old enrolled in the French National Histiocytosis Registry (1983-2023), 331 developed HI (median age at diagnosis: 1 year); median follow-up lasted 8.1 years. Bone-marrow aspirate smears and biopsies may show reactive histiocytes, hemophagocytosis or myelofibrosis but never confirm the diagnosis. Fifty-eight (17%) patients developed macrophage-activation syndrome, sometimes related to acute Epstein-Barr virus or cytomegalovirus infection, sometimes months before typical LCH manifestations appeared. Hemoglobin and platelet thresholds for initiating transfusion(s) appear to accurately distinguish 2 groups: mild HI (MHI; >7 g/dL and >20 G/L, respectively) and severe HI (SHI; ≤7 g/dL and ≤20 G/L). Each entity has different organ involvements, laboratory parameters, mutational status, blood BRAFV600E loads, drug sensitivities and outcomes (respective MHI and SHI 10-year survival rates: 98% and 73%). Since 1998, mortality first declined with combination Cladribine-cytarabine therapy, and then with mitogen-activated protein-kinase inhibitors since 2014. Forty-one (12%) patients developed neurodegenerative complications that have emerged as a risk for long-term survivors. These results suggest limiting the HI-RO definition to SHI, as it encompasses almost all medical complications of LCH. Future clinical trials might demonstrate that targeted-therapy approaches would be better adapted for these patients, while MHI can be managed with classic therapies. (Copyright © 2024 American Society of Hematology.)
Databáze:	MEDLINE
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