Clinical Outcome and Quality of Life in Patients with ARPC1B Deficiency Managed Conservatively or with Allogeneic Hematopoietic Stem Cell Transplantation
Notice bibliographique
Résumé
Background ARPC1B deficiency leads to a combined immunodeficiency characterized by early clinical onset, recurrent infections, and platelet abnormalities with bleeding tendency. Although most patients with ARPC1B mutations tolerate transplant conditioning, with a high rate of immunodeficiency resolution, there is a lack of studies comparing the clinical outcome and quality of life of patients undergoing transplantation or treated conservatively. The aim of the study is to compare ARPC1B patients managed conservatively and with HSCT assessing clinical outcome and quality of life. Methods The study was approved by ESID, EBMT, and CIS inborn error working parties. The inclusion criteria are patients with ARPC1B deficiency genetically confirmed and treated conservatively or with HSCT. Clinical data including symptoms, genetics, IDDA 2.1 score at last follow-up, and HSCT-related features were collected by local physicians and anonymized. Patients included in the study completed age-related quality of life questionnaires: PedsQL 4.0 and SDQ for children and SF 12 for adults, respectively. Results Thirteen centers from nine countries have been involved, collecting data from 20 patients. Clinical onset was early in all patients (median age 1 month [0-36]). The most frequent homozygous variant was c.311G>C (20%). Eight out of the 20 patients (40%) received allo-HSCT at a median age of 8.8 years [0.76-16.2]. The main clinical features are summarized in Table 1. At last available follow-up, 17 out of 20 patients are alive (85%), with 3 out of 8 patients dead after transplant. The median age at follow-up was 10.41 (1.58-36) for non-transplanted and 14.85 years (0.83-22.2) for transplanted patients. At the time of writing, 10 out of 17 patients (58.8%) had completed the QoL questionnaire (8/12 not transplanted, 2/5 transplanted). Preliminary results from the quality of life questionnaires are highlighted in Figure 1A-B. Table 1. HSCT No-HSCT Total n n=8 100% n=12 % n=20 (100) Infections 8 100 11 92 19 (95%) Recurrent AOM 4 50 9 75 13 (65%) URTI 5 62.5 3 25 8 (40%) LRTI 5 62.5 6 50 11 (55%) Sepsis 3 37.5 0 0 6 (30%) CNS infections 0 0 1 8 3 (15%) Skin infections 6 75 9 75 15 (75%) Severe Warts 2 25 4 33 6 (30%) Acute/Chronic CMV 2 25 4 33 7 (35%) Bleeding 3 37.5 8 67 11 (55%) Enterorrhagia 3 37.5 7 58 10 (50%) Recurrent epistaxis 0 0 2 17 2 (10%) ITP 3 37.5 3 25 6 (30%) Severe eczema 6 75 8 67 14 (70%) Skin vasculitis 2 25 5 42 7 (35%) Arthritis 2 25 4 33 6 (30%) Lymphoproliferation 2 25 1 8 3 (15%) IBD-like 2 25 4 33 6 (30%) Last follow-up IDDA 2.1 score 32.9 [4.1-174] 33.9 [6.9-66] 32.9 [4.1-174] HSCT: Hematopoietic Stem Cell Transplantation; AOM: Acute Otitis Media; URTI: Upper Respiratory Tract Infection; LRTI: Lower Respiratory Tract Infection; CNS: Central Nervous System; CMV: Cytomegalovirus; ITP: Immune Thrombocytopenic Purpura; IBD: Inflammatory Bowel Disease; IDDA: Inflammatory Disease Damage Assessment Figure 1. Patient (A) and proxy (B) PedsQL 4.0 scales scores of pediatric patients with ARPC1B deficiency. Scores are compared with children with healthy pediatric population. Conclusion Preliminary results confirm that HSCT in ARPC1B deficiency is feasible and effective. Even if preliminary, QoL was significantly reduced in patients treated conservatively compared with healthy donors. Notably, there is a marked reduction in the frequency of bleeding, eczema, and autoimmune/autoinflammatory symptoms in the HSCT group. More data are needed to determine its impact on patient outcomes and quality of life.
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 | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| 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 ».