Treatment Strategies and Outcomes of the Rare Histiocytic Disorders: Long-Term Results of the International Rare Histiocytic Disorders Registry (IRHDR)
Notice bibliographique
Résumé
Background: Rare histiocytic disorders (RHDs) are diverse myeloid neoplasms that include Juvenile xanthogranuloma (JXG), Erdheim-Chester Disease (ECD), Rosai-Dorfman disease (RDD), Malignant histiocytoses (MH), ALK+ histiocytosis, indeterminate cell histiocytosis (ICH) and mixed histiocytosis (MXH). Methods: IRHDR data were collected retrospectively and prospectively including clinical features, diagnosis with central pathology (CP) review, treatments and outcomes. Descriptive statistics of data registered during the first 9 years are presented. Results: From April 2015 - June 2024, 214 patients were enrolled, 133 completed CP review; 111 confirmed RHD and 22 excluded. We present 192 RHD patients; median age at diagnosis was 11 years (0.11-77 years), 112 (58.3%) were males. JXG family patients (n=66): 2 KRAS+, 1 BRAF-other+, 1 MAP2K1+, 1 CSFR1+. Thirty-six were cutaneous (2 had JMML): 11 (31%) did well with observation, and 13 (36%) severe cases responded well to surgery +/- steroids. One progressive nodular had partial response (PR) to MEK-inhibitor (MEK-I). Five had reticulohistiocytoma: 2 had observation (complete response - CR), and 2 oral chemotherapy (1 PR; 1 resistant had PR after everolimus). Sixteen were systemic: 3 (19%) had vinblastine/steroids - LCH-III (CR), 1 surgery (CR), and 2 observation (1 CR; 1 stable disease - SD); 7 (44%) had relapsed/refractory (R/R) disease: 2 had cladribine or surgery (PR), and 5 others were refractory to cladribine or clofarabine (1 PR after MEK-I). Two systemic JXG were post-ALL, 1 died from toxicity and 1 is alive (SD). Three had adult JXG: 2 musculoskeletal had surgery/observation (CR), and 1 cutaneous had RET-kinase inhibitor (CR). Five intraocular: 3 had surgery (CR/PR), 2 resistant to oral chemotherapy had MEK-I (1 CR; 1 SD after intrarterial melphalan). ECD patients (n=41): 16 BRAF-V600E+, 3 MAP2K1+, 1 KRAS+. Five were localized, 19 systemic, and 15 CNS. BRAF/MEK-I induced more responses (81% overall response rate - ORR) than conventional therapies (interferon-α, chemotherapy, anakinra, radiation; 55% ORR) as first-line or salvage therapy. RDD patients (n=51): 2 BRAF-V600E+, 2 KRAS+, 1 MAP2K1+. Twenty-four were nodal: 7 (29%) had observation (SD), 12 (50%) had surgery +/- steroids (variable responses), 1 had clofarabine (PR), and 1 had chemotherapy followed by MEK-I (died from progressive disease - PD). Twenty-seven were systemic: 11 (41%) had oral chemotherapy (73% ORR), 3 (27%) R/R had cladribine (all PR); 2 had surgery (75% ORR), 5 observation (40% ORR); 2 had indomethacin or radiotherapy (SD); 5 (19%) R/R received BRAF/MEK-I (60% ORR); 1 refractory to surgery and cladribine (died from PD). MH patients (n=16): 3 KRAS+, 1 BRAF-V600E+. Twelve histiocytic subtype, 2 Langerhans cell, 1 interdigitating cell and 1 indeterminate cell tumour. Eight MH were localized: 3 had surgery +/- chemotherapy (2 CR, 1 relapse had PDL-1 inhibitor), 3 steroids +/- chemotherapy (1 CR, 1 SD, 1 PD with CR after cladribine). One R/R to cladribine/radiotherapy (SD), and 1 post-ALL MH was refractory to cladribine (died from PD). Seven MH were systemic: 3 had ALL-like therapy (2 CR, 1 SD), 2 chemotherapy + steroids (1 SD, 1 died from PD), and 1 had MEK-I (PR then relapsed). One with CNS+ MH had surgery followed by BRAF/MEK-I (CR). ALK+ histiocytosis patients (n=7): 5 localized: 2 musculoskeletal had observation (1 CR, 1 SD), 1 ocular had crizotinib (PR), 1 localized to the trachea had surgery (CR). Two CNS+ had LCH-III +/- surgery (1 CR; 1 R/R had PR to lorlatinib then relapsed). ICH patients (n=6): 1 BRAF-V600E+, 1 BRAF-other+, 1 MAP2K1+. 100% ORR was seen in 4 localized with observation or steroids, and 2 systemic/CNS with LCH-III. MXH patients (n=5): 2 BRAF-V600E+, 1 BRAF-other+, 1 MAP2K1+. One had localized RDD/LCH, 4 were systemic: 3 ECD/LCH, 1 ECD/RDD. Most MXH were refractory to conventional therapies, with durable responses to BRAF/MEK-I. After a median follow-up of 29.6 months, 94.8% of patients (n=182) are alive in CR/SD. Event-free survival is 84%; 28 (15%) relapsed. Five patients died, 4 from PD, and 1 from toxicity. Conclusions:RHDs are characterized by pathological, clinical and molecular diversity, with variable responses to conventional therapies. Most refractory systemic cases respond to ALK/BRAF/MEK-I. Further mutational analysis may identify novel targeted therapies, which could be helpful for resistant RHDs.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».