China
Africa
Explore chapters and articles related to this topic
Cutaneous Lymphomas
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Emily Correia, Shalini Krishnasamy, Neda Nikbakht
Clinical presentation: SPTL may present in both children and adults and affects both sexes equally. Typically, patients present with solitary or multiple nodules and plaques that commonly arise on the legs (Figure 22.7). Fever, fatigue, and weight loss may accompany the lesions, while ulceration of lesions and dissemination to extracutaneous sites is uncommon. A life-threatening hemophagocytic lymphohistiocytosis (HLH) may seldom occur and can correspond with a rapidly progressive course. The diagnosis of SPTL may be preceded by a seemingly benign panniculitis.
Clinical Applications of Gene Therapy for Immuno-Deficiencies
Published in Yashwant Pathak, Gene Delivery, 2022
Khushboo Faldu, Sakshi Gurbani, Jigna Shah
Hemophagocytic lymphohistiocytosis (HLH) can be fatal. The symptoms include cytopenias, hyper inflammation, splenomegaly, and uncontrolled immune activation [63]. HLH can be caused due to various underlying conditions, like familial hemophagocytic lymphohistiocytosis (FHL), autoimmunity, infection, or malignancy. Defects in the functioning of cytotoxic T- and NK-cells, together with autosomal recessive alterations in syntaxin 11 (STX11), MUNC 13-4 [Protein unc-13 homolog D (UNC13D)], and perforin (PRF1) result in the development of FHL. The most common cause is PRF1 mutations. AlloHSCT is the preferred treatment modality for genetically mutated or relapsed refractory HLH patients [64, 65]. Etoposide, with or without cyclosporine and glucocorticoids, are a part of the standard of care, but lack adequate disease control in 40% of patients [66]. Emapalumab, an anti-interferon gamma (IFNγ) monoclonal antibody, has been approved as second-line therapy for primary HLH in the USA, as IFNγ plays a central role in pathogenesis in HLH, with levels correlating with active disease [67, 68]. Alemtuzumab and Janus kinase (JAK) inhibitors are being tested for improving remission and allowing progress to HSCT [69–74]. Alemtuzumab with corticosteroids and cyclosporine has provided favorable safety and efficacy in children suffering from primary HLH (91.6% survived to alloHSCT) [74]. HSC-GT and T-cell strategies are being developed for the treatment of FHL [75–79].
Histiocytosis and Lipid Storage Diseases
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Salwa Shabbir Sheikh, David F. Garvin
All the following criteria are required to diagnose hemophagocytic lymphohistiocytosis (HLH): Fever, splenomegaly, cytopenia, hypertriglyceridemia, and/or hypofibrinogenemiaHemoglobin <9 g/L, platelet <100 × 109L, neutrophils <1.0 × 109 g/LHistopathologic criteria—hemophagocytosis in the bone marrow, spleen, or lymph nodes
Secondary hemophagocytic lymphohistiocytosis in pediatric patients: a single center experience and factors that influenced patient prognosis
Published in Pediatric Hematology and Oncology, 2019
Melahat Melek Oguz, Gurses Sahin, Esma Altinel Acoglu, Emine Polat, Husniye Yucel, Fatma Zehra Oztek Celebi, Hilal Unsal, Meltem Akcaboy, Eyup Sari, Saliha Senel
Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation. The pathogenetic mechanisms behind HLH are not completely understood but involve defective granule-mediated cytotoxicity and uncontrolled T-cell activation that is induced by hypercytokinemia. HLH is classified as a primary (familial) and secondary (acquired) disease. Primary HLH, also termed familial hemophagocytic lymphohistiocytosis (FHL), is an autosomal recessive genetic disorder defined by mutations in the following genes: PRF1 in familial hemophagocytic lymphohistiocytosis type 2 (FHL2), UNC13D in familial hemophagocytic lymphohistiocytosis type 3 (FHL3), STX11 in familial hemophagocytic lymphohistiocytosis type 4 (FHL4), and STXBP2 in familial hemophagocytic lymphohistiocytosis type 5 (FHL5). On the other hand, some patients with other congenital immune deficiencies [X-linked lymphoproliferative disorder, Griscelli syndrome, Chédiak–Higashi syndrome (CHS), and Hermansky–Pudlak syndrome (HPS)] may develop HLH with major causative genes, namely, SH2D1A/BIRC4, RAB27A, LYST, and ADTB3A.[1] Secondary HLH is associated with viral, bacterial, fungal, and parasitic infections, autoimmune disease and malignant disorders in patients without an identifiable underlying genetic trigger.[2]
Multivariate analysis of prognosis for patients with natural killer/T cell lymphoma-associated hemophagocytic lymphohistiocytosis
Published in Hematology, 2018
Zhili Jin, Yini Wang, Jingshi Wang, Lin Wu, Ruijun Pei, Wenyuan Lai, Zhao Wang
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder characterized by high inflammatory cytokines production induced by excessive immune activation. HLH can be divided into primary disease, which is characterized by cell dysfunction due to gene mutation; and secondary HLH which is secondary to infection, autoimmune diseases, malignant tumors, and other causes [1–3]. Letendre and co-workers [4] examined 62 cases of HLH patients, and found that tumor-related HLH was the most common cause, accounting for 52% of patients with HLH. Furthermore, Rivière et al. [5] studied 162 cases of HLH patients, and demonstrated that hematological malignancies, especially non-Hodgkin’s lymphoma, were one of the main cause of hemophagocytic syndrome, accounting for 56% incidence. These data suggest that malignant tumors; especially non-Hodgkin’s lymphoma is one of the most common risk factors of HLH. Moreover, in LAHS patients, NK/T cell lymphoma hemophagocytic lymphohistiocytosis (NK/T-LAHS) subtype is one of the most common pathology, accounting for up to 35% of the LAHS patient population [6].
Antibodies to watch in 2018
Published in mAbs, 2018
Hélène Kaplon, Janice M. Reichert
Emapalumab (NI-0501) is a human mAb that targets interferon gamma (IFNγ). It is under investigation as a treatment for primary hemophagocytic lymphohistiocytosis, a hyperinflammatory condition characterized by the overwhelming activation of normal T lymphocytes and macrophages, which leads to clinical and hematologic alterations and death in the absence of treatment. NovImmune SA has received a variety of designations for emapalumab that are intended to facilitate the development of drugs, including Priority Medicines and orphan drug designations in the EU, and Breakthrough Therapy, rare pediatric disease, and orphan drug designations in the US. The Phase 2/3 NCT01818492 study investigating the safety, tolerability, PK and efficacy of multiple IV administrations of emapalumab in children (up to 18 years old) with primary hemophagocytic lymphohistiocytosis is recruiting patients. The primary outcome measure is the overall response rate, the estimated enrollment is 32 patients, and the primary completion date of the NCT01818492 study is December 2017. In addition, a Phase 3 (NCT03312751) study of emapalumab is due to start in January 2018. This study, which has an estimated enrollment of 34, will assess the efficacy, safety, impact on quality of life, and long-term outcome of emapalumab in pediatric patients (up to 18 years old) with primary hemophagocytic lymphohistiocytosis. The primary outcome measure is overall response at week 8 or end of treatment (if earlier), and the estimated primary completion date is June 2019.