Real World Outcomes in Adult Histiocytosis: 23-Year Canadian Single Center Analysis
Notice bibliographique
Résumé
Background: Adult histiocytic disorders are rare. Existing knowledge has largely been extrapolated from the pediatric counterparts. Langerhans Cell Histiocytosis (LCH), Erdheim Chester Disease (ECD) and Rosai-Dorfman Disease (RDD) are three most encountered histiocytic disorders. This study aimed to address the paucity of data on the clinical findings and outcomes in adult histiocytic disorders. Methods: Using REB approved Princess Margaret Cancer Center database, we did a retrospective analysis on adult patients (aged >18 years) with histiocytic disorders presenting to our center from January 2000 to June 2023. Results: We identified 96 patients with various primary adult histiocytic disorders. Median age was 45.5 (range 18-80) years; 54 (56%) were males. LCH constituted the majority at 62% (n=60), followed by RDD 20% (n=19), ECD 11% (n=11) and non-LCH histiocytosis 7% (n=6) patients. Unisystem involvement occurred in 34 (57%) LCH patients; isolated bone in 18 (30%), primary pulmonary LCH in 9 patients (15%), isolated skin/subcutaneous in 3 (5%) and, lymph node in 1 patient. Multisystem LCH occurred in 26 (43%) patients; >2 organ systems were involved in 11 (18%) patients. Sixteen patients (27%) patients had high-risk organ (HRO) involvement defined as involvement of spleen, liver, CNS, or bone marrow. Twelve (20%) patients had CNS involvement; diabetes insipidus in 11 (18%) patients. History of smoking was significantly elicited in patients with LCH compared to ECH or RDD. (67% vs 13% vs 16%; p<0.0001). Although BRAF V600E positivity was low (28%; available in 36 patients) in our cohort, it was equally distributed amongst unisystem (33%) and multisystem (24%) disease. (p= 0.51). Amongst ECD patients, common (often overlapping) presentations included retroperitoneal or mediastinal fibrosis in 6, exophthalmos secondary to periorbital infiltration in 4 and cerebellar symptoms (ataxia and dysarthria) in 3 patients. Surprisingly, bone involvement was only seen in 36% of the patients. BRAF V600E mutation was positive in 7 (70%) of the 10 patients with available results. Classic nodal involvement was seen in only 8 (42%) of RDD patients and extranodal involvement included subcutaneous masses (n=5), CNS involvement (n=4) and visceral involvement (n=4). Preferred management strategies for unisystem LCH included surgical intervention (n=25), localised radiation (n=4) or “wait and watch” along with smoking cessation (n=14). Systemic cladribine was the given in 15 multisystem LCH patients- 9 received as first line and 6 in subsequent lines. Overall response rates (ORR) after first line of therapy were significantly better in patients with unisystem (76%) compared to multisystem (52%) disease (p=0.049). Twenty (33%) LCH patients required subsequent lines of therapies with four patients receiving targeted therapies (Cobimetinib-3; vemurafenib-1); all these patients attained at least a partial response. Various first line systemic therapies given in ECD were cladribine (n=1), interferon alfa (n=5), anakinra (n=3), vemurafenib (n=1) with ORR of 40%. Eight patients (72%) required subsequent therapies with cladribine in 4, vemurafenib in 2 and dabrafenib and trametinib combination in 2 patients. RDD was managed with systemic steroids in 8 (42%) patients while 4 patients underwent diagnostic surgical excision of the tumour. Concurrent or subsequent hematological malignancies were seen in 3 (5%; included Acute Myeloid Leukemia (AML), Hairy Cell Leukemia (HCL) and JAK2 positive Myeloproliferative Neoplasm (MPN)) LCH patients, 3 ECD patients (CALR mutated MPN, JAK2 positive MPN, Chronic Lymphocytic Leukemia) and 2 RDD patients (AML and MPN). At median follow up of 39.5 months (range 1- 266; IQR-15-96), median Overall Survival (OS) of our cohort was 206 months with 2-year and 5-year OS of 96% and 88% respectively. Although patients with ECD had inferior 5-year OS (79%) compared to patients with LCH (96%) or RDD (86%), it was not statistically significant. (p=0.179) Conclusion: High suspicion is needed in the background of appropriated clinical context since clinical presentation varies widely in adult histiocytic disorders. High incidence of second hematological malignancies in our small cohort warrants more efforts to establish the association between the two entities. Prospective, multicenter studies with molecular discoveries are needed in adult counterpart of this orphan disease.
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 | 0,002 | 0,005 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,005 | 0,011 |
| Études des sciences et des technologies | 0,002 | 0,001 |
| Communication savante | 0,002 | 0,001 |
| Science ouverte | 0,002 | 0,002 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».