Although reduced within the past decade, the delay of diagnosis of common variable immunodeficiency remains unacceptable. Recurrence of upper respiratory tract infection or pneumonia should lead to systematic evaluation of serum immunoglobulin.

Preemptive treatment increased the incidence of invasive fungal disease, without increasing mortality, and decreased the costs of antifungal drugs. Empirical treatment may provide better survival rates for patients receiving induction chemotherapy.

IntroductionThe geographic heterogeneity in the incidence of B-cell nonHodgkin lymphomas (NHLs) suggests that environmental factors such as infections might have a role in lymphomagenesis. 1,2 Because of the inherent genetic instability of lymphocytes, lymphoid proliferation increases the risk of transformation, and sustained activation of the lymphoid system, which can be observed during chronic infection, immunodeficiency, and autoimmunity, constitutes a risk factor for lymphomas. [3][4][5] Congenital and acquired immunodeficiencies associated with HIV infection and solid organ or hematopoietic transplantation increase the risk of developing B-cell NHLs. 6,7 Similarly, Sjögren syndrome and other autoimmune conditions are also associated with an increased risk of lymphomas. 8,9 Certain types of lymphomas are associated with specific microbial infections, and infection-associated lymphomas currently fall in diverse histopathologic categories (Table 1). 10 Infections may contribute to lymphomagenesis by promoting favorable conditions for lymphocyte transformation, such a increased proliferation or decreased apoptosis of lymphoid cells. 11 Direct lymphocyte transformation by a given microbial agent is the simplest scenario accounting for infection-associated lymphomas. Lymphotropic transforming viruses such as Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and human Tlymphotropic virus 1 (HTLV-1) directly infect a subset of lymphoid cells in which they express viral oncogenes. [12][13][14] An alternative scenario to direct transformation of lymphocytes has more recently emerged for microbial species associated with lymphomas but that do not directly infect or transform lymphoid cells. They have in common the ability to persist chronically in host tissues and trigger a sustained lymphoid proliferation, giving a selective advantage to lymphoid clones that still remain dependent upon antigen stimulation. 15,16 According to this model, the microbial pathogen is neither intrinsically transforming nor oncogenic, but can be viewed as a chronic source of antigens increasing the proliferative rate of lymphoid effectors, hence fueling the transformation process. This model has emerged with the description of several lymphomas developing in the context of chronic antigen-dependent immune stimulation, among which H pylori-associated gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the best characterized 15,17,18 (Figure 1). Precise elucidation of the mechanisms underlying this "indirect" lymphomagenesis as well as completion of the inventory of the microbial species driving these antigen-dependent lymphoproliferations may provide important clues for their early diagnosis and the rationalization of the therapeutic interventions for this subtype of lymphomas.This group of lymphomas often involves extranodal sitesnormally devoid of organized lymphoid tissue-and manifests initially as indolent low-grade proliferations, reminiscent of the normal lymphoid hyperplasia driven by a physiologic antigenic stimulation....

Several distinctive features differentiate CVID enteropathy from other causes of enteropathy including CS. Replacement i.v. Ig therapy is insufficient to improve gastrointestinal symptoms. Steroids are effective in reducing inflammation and restoring mucosal architecture.

IntroductionExtranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare and severe malignancy. It is more frequent in Asia and Central/South America than in Europe and North America. It is thought to arise from NK cells or, occasionally, from a subset of ␥␦ or ␣␤ cytotoxic T cells, and shows a tight association with Epstein-Barr virus (EBV). It is classically characterized by a cytoplasmic CD3 ⑀ phenotype, with no surface CD3 or T-cell receptor expression, no T-cell receptor gene rearrangements, an activated cytotoxic profile with perforin, granzyme B, and TIA-1 expression, and frequent CD56 expression. [1][2][3] Extranodal NK/T-cell lymphoma is usually diagnosed in adults, with a median age in the fifth decade. The nasal cavity or other parts of the upper aerodigestive tract are primarily involved, but some cases occur at extranasal sites. The term "nasal-type" is used in the World Health Organization classification to describe forms arising both in the nasal cavity and in extranasal sites. 3,4 Because disease incidence is rare even in prevalent areas, there has been no randomized controlled trial, and most treatment protocols are consensus-guided. 5 Localized NK/T-cell lymphomas often respond to radiotherapy 6,7 or to concurrent radiation and chemotherapy, 8 but relapse is common. Chemotherapy protocols used for lymphomas of other histologic subtypes are poorly effective, at least in part, because of frequent multidrug resistance gene expression by tumor cells. 9 Patients with disseminated or relapsing disease have a very poor outcome, 4,10,11 and there is no standard management for relapsed or refractory disease. We and others, in small retrospective studies, 12-16 have observed very good response and survival rates in patients treated with L-asparaginase, a drug with an original antitumoral mechanism not affected by MDR. NK cells lack asparagine synthase activity, and asparaginase has been shown to induce apoptosis of tumoral NK cells in vitro. 17 These findings provided the rationale for this open-label phase 2 study of an L-asparaginase-containing regimen for patients with relapsed and/or refractory extranodal NK/T-cell lymphoma. We chose to combine L-asparaginase with methotrexate, a drug insensitive to the multidrug resistance pathway, because of its well-known synergistic effect with asparaginase in acute lymphoblastic leukemia and its ability to prevent central nervous system involvement. Dexamethasone was added because T-cell lymphomas are usually sensitive to corticosteroids and dexamethasone For personal use only. on May 12, 2018. by guest www.bloodjournal.org From seems to be associated with a lower risk of thrombosis when given with L-asparaginase. 18 Methods PatientsThe patients were at least 18 years of age, with relapsed or refractory extranodal NK/T-cell lymphoma. Eligibility criteria included biopsyproven diagnosis of NK/T-cell lymphoma, nasal-type, irrespective of the anatomic site. Malignant cells in all cases had a CD3⑀ ϩ , CD20 Ϫ phenotype, a cytotoxic profile, and evidence of E...

These results indicate that campylobacter and immunoproliferative small intestinal disease are associated and that C. jejuni should be added to the growing list of human pathogens responsible for immunoproliferative states.

Our results provide the basis for a detailed prospective evaluation of autoimmunity and inflammation in the context of PIDs, with a view to accurately assessing these risks and describing the possible effect of medical intervention.

Heterozygous germline GATA2 mutations strongly predispose to leukemia, immunodeficiency, and/or lymphoedema. We describe a series of 79 patients (53 families) diagnosed since 2011, made up of all patients in France and Belgium, with a follow up of 2249 patients/years. Median age at first clinical symptoms was 18.6 years (range, 0-61 years). Severe infectious diseases (mycobacteria, fungus, and human papilloma virus) and hematologic malignancies were the most common first manifestations. The probability of remaining symptom-free was 8% at 40 years old. Among the 53 probands, 24 had missense mutations including 4 recurrent alleles, 21 had nonsense or frameshift mutations, 4 had a whole-gene deletion, 2 had splice defects, and 2 patients had complex mutations. There were significantly more cases of leukemia in patients with missense mutations (n=14 of 34) than in patients with nonsense or frameshift mutations (n=2 of 28). We also identify new features of the disease: acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, fatal progressive multifocal leukoencephalopathy related to the JC virus, and immune/inflammatory diseases. A revised International Prognostic Scoring System (IPSS) score allowed a distinction to be made between a stable disease and hematologic transformation. Chemotherapy is of limited efficacy, and has a high toxicity with severe infectious complications. As the mortality rate is high in our cohort (up to 35% at the age of 40), hematopoietic stem cell transplantation (HSCT) remains the best choice of treatment to avoid severe infectious and/or hematologic complications. The timing of HSCT remains difficult to determine, but the earlier it is performed, the better the outcome.