No abstract

Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma Re-induction rates and event-free survival (EFS) for paediatric patients with relapsed or refractory T-cell acute lymphoblastic leukaemia (ALL) are known to be worse than their pre-B cell counterparts. A review of children with ALL who relapsed after being treated on upfront Children's Cancer Group (CCG) ALL protocols showed a 5-year EFS of 37% for B-cell lineage, but only 23% for T-cell lineage (Nguyen et al, 2008). A major challenge is getting this population into a second remission (CR2). On a recent intensive re-induction platform only two of seven patients (29%) with early relapse (<18 months from diagnosis) of T-cell ALL obtained a CR2; whereas 43 of 63 pre-B cell ALL (68%) went into a second remission . Patients with relapsed T-cell lymphoblastic lymphoma (LL) also have poor CR2 and EFS rates (Burkhardt et al, 2009). The Berlin-Frankfurt-Münster group classifies T-cell relapses as higher risk than their B-lineage counterparts while the Children's Oncology Group (COG) does not separate T from B lineage at relapse, although T-cell immunophenotype was found to be unfavourable in recent COG retrospective reviews of relapse (Barrett et al, 1994;Gaynon et al, 1998). Alternative strategies are needed to treat relapsed and refractory T-cell ALL/LL. Nelarabine (AraG), a purine nucleoside antimetabolite, was approved in 2005 for treatment of acute T-cell ALL/LL in patients of all ages. An overall response rate of 41% was seen in a study of 26 adult patients with T-cell ALL and 13 patients with T-cell LL (DeAngelo et al, 2007). In a combined adult and paediatric phase 1 study, patients with T-cell ALL had a response rate of 54%; although T-cell LL patients only had a 13% response rate . A single agent Phase II paediatric trial in children with refractory T-cell haematological malignancies showed a 48% CR2 rate and a 23% CR3 rate for T-cell ALL (Berg et al, 2005). As a result of toxicity, the dose of AraG had to be de-escalated from the maximal tolerated dose found in the Phase 1 paediatric studies (1. In all studies, grade 3 or 4 neurotoxicity was the dose limiting toxicity. Grade 3 and 4 neurotoxicity documented in paediatric subjects included headache, somnolence, hypoesthesia, seizure, and ataxia, and were usually reversible. A third of patients had peripheral sensory and/or motor neuropathy, but only rarely at grade 3 or higher. Other toxicities included haematological, fatigue, musculoskeletal weakness or pain, and nausea/vomiting (Berg et al, 2005;Kurtzberg et al, 2005;Cohen et al, 2008;DeAngelo, 2009).The combination of etoposide (VP) and cyclophosphamide (CPM) is used widely for refractory and relapsed lympho- (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensor...

Transcriptomic analyses of CF airway epithelia, coupled to genomic (GWAS) analyses, highlight the role of heritable host defense variation in determining the pathophysiology of CF lung disease. The identification of these pathways provides opportunities to pursue targeted interventions to improve CF lung health.

Accurate segmentation of the hippocampus from infant MR brain images is a critical step for investigating early brain development. Unfortunately, the previous tools developed for adult hippocampus segmentation are not suitable for infant brain images acquired from the first year of life, which often have poor tissue contrast and variable structural patterns of early hippocampal development. From our point of view, the main problem is lack of discriminative and robust feature representations for distinguishing the hippocampus from the surrounding brain structures. Thus, instead of directly using the predefined features as popularly used in the conventional methods, we propose to learn the latent feature representations of infant MR brain images by unsupervised deep learning. Since deep learning paradigms can learn low-level features and then successfully build up more comprehensive high-level features in a layer-by-layer manner, such hierarchical feature representations can be more competitive for distinguishing the hippocampus from entire brain images. To this end, we apply Stacked Auto Encoder (SAE) to learn the deep feature representations from both T1-and T2-weighed MR images combining their complementary information, which is important for characterizing different development stages of infant brains after birth. Then, we present a sparse patch matching method for transferring hippocampus labels from multiple atlases to the new infant brain image, by using deep-learned feature representations to measure the inter-patch similarity. Experimental results on 2-week-old to 9-month-old infant brain images show the effectiveness of the proposed method, especially compared to the state-of-the-art counterpart methods.

Benign cystic epithelial inclusions with squamous, glandular, or Müllerian phenotypes are known to occur in the axillary lymph nodes of patients with benign and malignant breast disease. Careful evaluation of hematoxylin and eosin-stained slides and correlation with the histologic findings in the ipsilateral breast are paramount in evaluation of suspected benign inclusions. In this case of ductal carcinoma in situ (DCIS) of the breast in a 73-year-old woman, DCIS also involved epithelial inclusions in an ipsilateral axillary lymph node. The recognition of these benign epithelial elements, and awareness that they can be involved by DCIS, is crucial to avoid the overdiagnosis of metastatic carcinoma.