Facteurs prédictifs du chimérisme après greffe non apparentée de cellules souches de sang placentaire chez l'enfant

L'objectif de ce travail était de décrire la probabilité de survenue d'un chimérisme complet de type donneur (cDC, >99,9% donneur) après une greffe non apparentée de cellules souches de sang placentaire chez l'enfant, d'en identifier les facteurs prédictifs ainsi que son impact sur le devenir post greffe. 94 enfant greffes par une unité de sang placentaire après préparation myeloablative, ont été inclus dans notre étude. Le chimérisme, quantifié sur sang périphérique selon la technique TAQMAN (sensibilité de 0,1%) a été recueilli de manière séquentielle une période de 3 ans post greffe. L'incidence cumulative de survenue d'un chimérisme >99,9% donneur à 1 an est de 61,8%. Lors de l'analyste multivariée, 3 facteurs prédictifs ont été mis en évidence: le caractère malin de la pathologie initiale (p=0,03) l'âge avec comme facteur péjoratif un âge à la greffe inférieur à 2,16 ans (correspondant ua 1er quartile de notre étude, p=2,9.10-3) et la compatibilité HLA entre donneur et receveur (p=8,7.10-4), qui lorsqu'elle est moindre est associée à une probabilité plus importante d'apparition d'un chimérisme complet au cours du temps. Bien que la quantité cellulaire injectée ait un fort impact sur la reconstitution hématologique, elle ne semble pas influencer le chimérisme après greffe. Concernant le devenir post greffe, l'apparition d'un chimérisme complet précoce (c'est-à-dire un chimérisme >99,9% donneur dans le premier mois qui suit la greffe) apparaît prédictif de la prise de greffe (p=<0.10-3) mais aussi de la survenue de la maladie du greffon contre l'hôte (GvHD pour Graft versus Host Disease) à la fois aiguë et chronique. Aucune GvHD aiguë sévère ou chronique n'a été retrouvée chez les patients n'ayant jamais développé de chimérisme complet ce qui suggère qu'une hématopoïèse résiduelle même minime de type receveur protégerait de la survenue de GvHD après greffe de sang placentaireAIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Peripheral blood cells chimerism after unrelated cord blood transplantation in children: kinetics, predictive factors and impact on post-transplant outcome.

International audienceThis study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99*9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post-transplant outcome. Ninety-four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post-transplant dates, using a real-time polymerase chain reaction method with 0*1% sensitivity. Cumulative incidence of cDC at 1 year post-transplantation was 61*8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0*03), older age (above 2*16 years, the first quartile of age, P = 0*0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5-6/6, P < 0*001) increased the probability of post-transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99*9% donor chimerism on days 15-30 post-transplant) appeared useful to predict engraftment (P = 0*003) as well as acute and chronic graft-versus-host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ≤99*9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT

Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study

BACKGROUND: Activated phosphoinositide 3-kinase δ syndrome (APDS) 2 (p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency [PASLI]-R1), a recently described primary immunodeficiency, results from autosomal dominant mutations in PIK3R1, the gene encoding the regulatory subunit (p85α, p55α, and p50α) of class IA phosphoinositide 3-kinases. OBJECTIVES: We sought to review the clinical, immunologic, and histopathologic phenotypes of APDS2 in a genetically defined international patient cohort. METHODS: The medical and biological records of 36 patients with genetically diagnosed APDS2 were collected and reviewed. RESULTS: Mutations within splice acceptor and donor sites of exon 11 of the PIK3R1 gene lead to APDS2. Recurrent upper respiratory tract infections (100%), pneumonitis (71%), and chronic lymphoproliferation (89%, including adenopathy [75%], splenomegaly [43%], and upper respiratory tract lymphoid hyperplasia [48%]) were the most common features. Growth retardation was frequently noticed (45%). Other complications were mild neurodevelopmental delay (31%); malignant diseases (28%), most of them being B-cell lymphomas; autoimmunity (17%); bronchiectasis (18%); and chronic diarrhea (24%). Decreased serum IgA and IgG levels (87%), increased IgM levels (58%), B-cell lymphopenia (88%) associated with an increased frequency of transitional B cells (93%), and decreased numbers of naive CD4 and naive CD8 cells but increased numbers of CD8 effector/memory T cells were predominant immunologic features. The majority of patients (89%) received immunoglobulin replacement; 3 patients were treated with rituximab, and 6 were treated with rapamycin initiated after diagnosis of APDS2. Five patients died from APDS2-related complications. CONCLUSION: APDS2 is a combined immunodeficiency with a variable clinical phenotype. Complications are frequent, such as severe bacterial and viral infections, lymphoproliferation, and lymphoma similar to APDS1/PASLI-CD. Immunoglobulin replacement therapy, rapamycin, and, likely in the near future, selective phosphoinositide 3-kinase δ inhibitors are possible treatment options