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Purpose Pulmonary mucormycosis is a highly lethal invasive fungal infection usually found in immunocompromised patients. We report herein the case of an adult woman who developed pulmonary mucormycosis with possible systemic dissemination after recovering from acute liver failure secondary to acetaminophen overdose. Results Our case developed an invasive pulmonary mucormycosis with probable systemic dissemination. She did not suffer from any immunocompromising disease other than severe acute liver failure. She did not survive the disease, although she received appropriate antifungal treatment. We also performed a systematic review of the literature on pulmonary mucormycosis, with or without dissemination, in immunocompetent patients. We found 16 cases of pulmonary or disseminated mucormycosis in immunocompetent patients. Fifty-seven percent of them died and none occurred after an acute liver failure episode. Conclusion This case report is the first one to present an invasive pulmonary mucormycosis infection after acute liver failure in an adult patient. The clinical course of this disease is highly lethal, even in immunocompetent adults.

A 25-year-old man presented to the emergency department with a 3-day history of fever, anorexia, jaundice, and a generalized skin eruption. His liver function tests showed marked cholestatic and cytolytic abnormalities without liver insufficiency. A liver biopsy was performed, and morphology with routine stains was considered non-specific. Because of the dermatological findings, the non-specific biopsy morphology, and the absence of an identified infectious etiology, a diagnosis of Kawasaki disease was presumed. However, additional colorations on liver biopsy with Warthin–Starry stain revealed multiple thin and coiled microorganisms compatible with spirochetes. His serology for leptospirosis was found to be positive for IgM, supporting the diagnosis of acute leptospirosis with liver involvement. Our case illustrates the diagnostic challenge of leptospirosis and highlights the utility of conventional laboratory tests to confirm the diagnosis. Exceptionally, Warthin–Starry stain allowed the identification of leptospires in liver biopsy and confirmed liver involvement of systemic leptospirosis.

Acute Central Nervous System (CNS) Graft Versus Host Disease (GvHD) is a rare form of GvHD, only described in case reports. Knowledge about this condition is extrapolated from chronic CNS GvHD cases occurring mostly after hematopoietic stem cell transplantation. GvHD following solid organ transplantation is an unexpected complication. GvHD after liver transplantation has a poor prognosis, and the optimal management is not yet known. Here we describe the case of a 63-year-old man who underwent deceased donor liver transplantation and subsequently developed skin rash, colitis and pancytopenia followed by refractory status epilepticus. Following the identification of lymphocytes of donor origin in the cerebrospinal fluid of the patient, he was diagnosed with acute CNS GvHD. He was treated with an intensive immunosuppressive regimen, but care was withdrawn due to lack of improvement and worsening neurologic prognosis. It is the second known case of acute CNS GvHD following liver transplantation. Clinicians should be aware of this possible, although rare, complication of liver transplantation, especially when there is refractory status epilepticus of unknown origin.

Summary Background Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding Sanofi and Regeneron Pharmaceuticals.

An amendment to this paper has been published and can be accessed via the original article.

This is an update to the 2014 Canadian Hereditary Angioedema Guideline with an expanded scope to include the management of hereditary angioedema (HAE) patients worldwide. It is a collaboration of Canadian and international HAE experts and patient groups led by the Canadian Hereditary Angioedema Network. The objective of this guideline is to provide evidence-based recommendations, using the GRADE system, for the management of patients with HAE. This includes the treatment of attacks, short-term prophylaxis, long-term prophylaxis, and recommendations for self-administration, individualized therapy, quality of life, and comprehensive care. New to the 2019 version of this guideline are sections covering the diagnosis and recommended therapies for acute treatment in HAE patients with normal C1-INH, as well as sections on pregnant and paediatric patients, patient associations and an HAE registry. Hereditary angioedema results in random and often unpredictable attacks of painful swelling typically affecting the extremities, bowel mucosa, genitals, face and upper airway. Attacks are associated with significant functional impairment, decreased health-related quality of life, and mortality in the case of laryngeal attacks. Caring for patients with HAE can be challenging due to the complexity of this disease. The care of patients with HAE in Canada, as in many countries, continues to be neither optimal nor uniform. It lags behind some other countries where there are more organized models for HAE management, and greater availability of additional licensed therapeutic options. It is anticipated that providing this guideline to caregivers, policy makers, patients, and advocates will not only optimize the management of HAE, but also promote the importance of individualized care. The primary target users of this guideline are healthcare providers who are managing patients with HAE. Other healthcare providers who may use this guideline are emergency and intensive care physicians, primary care physicians, gastroenterologists, dentists, otolaryngologists, paediatricians, and gynaecologists who will encounter patients with HAE and need to be aware of this condition. Hospital administrators, insurers and policy makers may also find this guideline helpful.

Background: Treat-to-target therapy approaches are established for chronic diseases such as diabetes, hypertension, and more recently rheumatoid arthritis, resulting in improved patient outcomes. These approaches do not use patient reported outcomes (PRO) as targets of therapy. Chronic spontaneous urticaria (CSU), also called chronic idiopathic urticaria (CIU), is defined as recurrent urticaria of known and unknown cause, lasting more than 6 weeks. Treatment of CSU can be challenging. However, with the advent of proven therapies and validated instruments for measuring disease activity, the concept of treat-to-target (T2T) can be successfully applied to CSU. Herein, we propose a potential PRO therapeutic target and suggest a T2T approach for the management of patients with CSU. Methods: Principles and recommendations for a treat-to-target approach in CSU (T2T/CSU) were developed by a Canadian task force, consisting of dermatologists, immunologists, and allergists. The task force formulated recommendations for therapeutic targets in CSU on the basis of a systematic literature review and expert opinion. Results: The key features of these T2T/CSU recommendations are the use of a PRO as the principal target, with symptom control as measured by Urticaria Activity Score 7 (UAS7 ≤ 6), targeting symptom remission (UAS7 = 0). Conclusion: Treatment targets such as UAS7 ≤ 6 and UAS7 = 0 provide a benchmark for success in the care of patients with CSU, and will permit the evaluation of a PRO-based T2T approach in the care of these patients and the effect of this approach on improved patient care as seen in other chronic diseases.

Background IgPro20 (Hizentra®), a 20% subcutaneous immunoglobulin G (IgG), is an effective treatment for patients with primary immunodeficiencies with impaired IgG production. Flexible dosing regimens of IgPro20 have been supported by pharmacokinetic (PK) modeling and simulation. This study further describes the PK characteristics of serum IgG concentrations after weekly and biweekly administration of IgPro20 and compares predicted and actual serum IgG data using a previously-developed population PK (popPK) model. Methods A popPK model was developed by combining data from a previously-published model with data from a Phase 4 study (IgPro20_4005). An external validation of the original model using dosing, demographics, and historic endogenous serum IgG concentrations from patients enrolled in study IgPro20_4005 was performed. This dataset was then simulated 300 times and predicted serum IgG PK characteristics compared with the observed data. Results A total of 173 patients (156 unique patients from original model and 17 patients from study IgPro20_4005) provided 4078 observations of serum IgG concentrations. The popPK estimates obtained demonstrated a clearance (% inter-individual variability) of 0.138 L/day (35%), volume of central compartment of 3.95 L (78.6%), inter-compartmental clearance of 0.260 L/day (56%), and volume of peripheral compartment of 4.44 L. Validation results indicated that observed serum IgG concentration vs time data fell within the 90% prediction intervals for median, 25th, and 75th percentiles of the simulated IgG concentration time courses. Conclusions The present analysis validated the ability of the previously published popPK model to predict serum IgG concentration time profiles after biweekly subcutaneous IgPro20 administration.

An ectopic pancreas, also known as pancreatic rest or heterotopic pancreas, consists of pancreatic tissue found in a location with no continuity with the anatomic pancreas. This lesion can occasionally cause gastrointestinal obstruction, ulceration or become inflamed and cause ectopic pancreatitis. We present the case of a 29-year-old immunocompromised female patient due to a previous kidney transplant. She presented with nausea and vague abdominal discomfort and was admitted for investigation and treatment of an acute kidney injury. A small bowel mass of unknown etiology was incidentally found on abdominal computed tomography imaging. Due to the high suspicion of a post-transplant lymphoproliferative disease, a surgical exploration took place and revealed the presence of a pancreatic rest with chronic pancreatitis. Ectopic pancreas diagnosis is challenging and surgical exploration is warranted when a neoplastic process is suspected.

Item does not contain fulltext BACKGROUND: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. OBJECTIVE: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. METHODS: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. RESULTS: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%; median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16% (n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal (59%), or neurological features (29%). Eight affected mutation carriers had lymphoma, and 3 had gastric cancer. An EBV association was found in 6 patients with malignancies. CTLA4 mutations were associated with lymphopenia and decreased T-, B-, and natural killer (NK) cell counts. Successful targeted therapies included application of CTLA-4 fusion proteins, mechanistic target of rapamycin inhibitors, and hematopoietic stem cell transplantation. EBV reactivation occurred in 2 affected mutation carriers after immunosuppression. CONCLUSIONS: Affected mutation carriers with CTLA-4 insufficiency can present in any medical specialty. Family members should be counseled because disease manifestation can occur as late as 50 years of age. EBV- and cytomegalovirus-associated complications must be closely monitored. Treatment interventions should be coordinated in clinical trials.

Cronkhite-Canada syndrome is a rare syndrome consisting of extensive gastrointestinal polyposis and ectodermal changes including cutaneous hyperpigmentation, alopecia, and onychodystrophy. We report the case of a 45-year-old Caucasian male patient who failed multiple treatments over 2 years including steroids, azathioprine, adalimumab, and cyclosporine. He had recurrent and prolonged hospitalizations because of diarrhea, abdominal pain, weight loss, and malnutrition. Sirolimus was initiated with a significant clinical and endoscopic benefit apparent within, respectively, 2 and 8 weeks. An ongoing remission was achieved and maintained for over 6 months after prednisone tapering. We review the current evidence on treatment of Cronkhite-Canada syndrome and suggest the incorporation of sirolimus in that algorithm.

Introduction: Mastocytosis, a heterogeneous group of disorders, is characterized by an abnormal increase in the number of mast cells that is limited to the skin (cutaneous mastocytosis), involving extracutaneous tissues (systemic mastocytosis), or presenting as solid tumours (mastocytoma and mast cell sarcoma). Recent studies estimate that 1 in 10,000 people are diagnosed with mastocytosis. Although prompt diagnosis and appropriate management are crucial, little is known about the natural history and currently there are no established management guidelines. We have conducted a systematic review to assess the natural history and management of different mastocytosis subtypes. Methods: A systematic review and meta-analysis were conducted using the PubMed and Ovid database of studies published in English and French over the last fifteen years, from January 2001 to December 2016. Keywords ‘Cutaneous mastocytosis’, ‘Systemic mastocytosis’, ‘pathophysiology’, ‘clinical course’, ‘prognosis’, ‘drug therapy’, and ‘therapy’ were searched. Rate of complete resolution was subjected to pooled analysis for different mastocytosis subtypes. Meta-analysis was conducted using Stata version 12.0. Results: We reviewed 634 papers, of which 5 were included in the analysis of resolution, and 138 were included in the assessment of management. Pooled estimate for rate of complete resolution varied depending on the mastocytosis subtype. In cutaneous mastocytosis, the complete resolution rate for mastocytoma was 10% per year (95% CI: 4.8%, 15.1%) while the rate for urticaria pigmentosa was 1.9% per year (95% CI: −0.5%, 4.3%). Diffuse cutaneous mastocytosis and systemic mastocytosis subtypes did not show evidence of complete resolution in the studies reviewed. Treatment of cutaneous and systemic mastocytosis is purely symptomatic with topical corticosteroids, antihistamines, omalizumab and imatinib being common choices. Conclusion: Rate of resolution of mastocytosis is only shown in urticaria pigmentosa and mastocytoma. Better management guidelines are required to improve the health of these patients.

The aim of this paper is to study the group of elliptic units of a cyclic extension $L$ of an imaginary quadratic field $K$ such that the degree $[L:K]$ is a power of an odd prime $p$. We construct an explicit root of the usual top generator of this group, and we use it to obtain an annihilation result of the $p$-Sylow subgroup of the ideal class group of $L$.

Resume L’infection au Human T-cell leukemia virus type 1 ou HTLV-1 est un probleme de sante publique dans certaines regions endemiques telles que le Japon, l’Amerique centrale ou l’Afrique. Bien que la majorite des porteurs du HTLV-1 soient asymptomatiques durant toute leur vie, certains patients developpent des anomalies neurologiques, une arthropathie inflammatoire aussi appelee arthropathie associee a l’HTLV-1, voire une hemopathie lymphoide, la leucemie/lymphome a cellules T (LLT) qui a un pronostic tres reserve. L’arthropathie associee a l’HTLV-1 a ete decrite comme une entite proche de la polyarthrite rhumatoide mais caracterisee par une reponse pauvre ou nulle aux corticoides et aux Disease Modifying AntiRheumatic Drugs (DMARDs). L’utilisation des anti-TNF alpha chez ces patients constitue une alternative interessante mais souleve la question du risque de developpement de LLT. Nous rapportons le cas exceptionnel d’une patiente atteinte d’une forme indolente de LLT associee a une arthropathie liee a l’HTLV-1, refractaire aux corticoides, aux DMARDs et au rituximab, traitee avec succes par l’etanercept, sans passage a une forme agressive sur une periode de suivi de cinq ans.

We introduce two types of zeta functions (Ψ-type and ζ-type) of one complex variable associated to an arbitrary number field K. We prove various arithmetic identities which involve both of them. We also study their special values at integral arguments.

Let K be a real quadratic number field and let p be a prime number which is inert in K. We denote the completion of K at the place p by Kp. We propose a p-adic construction of special elements in Kp× and formulate the conjecture that they should be p-units lying in narrow ray class fields of K. The truth of this conjecture would entail an explicit class field theory for real quadratic number fields. This construction can be viewed as a natural generalization of a construction obtained by Darmon and Dasgupta who proposed a p-adic construction of p-units lying in narrow ring class fields of K.

Let K K be a real quadratic field, let p p be a prime number which is inert in K K and let K p K_p be the completion of K K at p p . As part of a Ph.D. thesis, we constructed a certain p p -adic invariant u ∈ K p × u\in K_p^{\times } , and conjectured that u u is, in fact, a p p -unit in a suitable narrow ray class field of K K . In this paper we give numerical evidence in support of that conjecture. Our method of computation is similar to the one developed by Dasgupta and relies on partial modular symbols attached to Eisenstein series.

In this paper we prove a functional equation for a certain class of zeta functions attached to an arbitrary number field K. The proof of the functional equation relies on the transformation formula of a multivariables theta function. The techniques which are used are classical and are due essentially to Riemann and Hecke. As a special case, we obtain a functional equation for partial zeta functions of K twisted by sign characters.

DRESS (drug reaction with eosinophilia and systemic symptoms) syndrome is a severe adverse drug-induced reaction. It manifests with pyrexia, eosinophilia, and lymphadenopathy, with multiple organ involvement, mainly the skin, liver, and kidneys. The purpose of this article is to demonstrate that DRESS syndrome can be associated with cerebral manifestations, a concept not well known in the neuroradiological literature. We describe three cases of DRESS syndrome associated with cerebral vasculitic-like lesions and realize a review of the literature to demonstrate that this association represents a very rare entity. Acute ischemic lesions were found among two patients. In all cases, perivascular enhancement was present. Magnetic resonance angiography (MRA) sequence was normal. Although no cerebral biopsy was performed, this enhancement pattern is strongly suggestive of a vasculitic process associated with DRESS syndrome. Diagnosis of cerebral vasculitic-like associated lesions must be considered in patients with DRESS syndrome since it can be reversed completely by withdrawing the causal medication and instigating corticosteroid treatment in a timely fashion.

Post-TAFA is an uncommon but serious complication of organ transplantation. This study aimed to compare the incidence of FA in CsA and tacrolimus-treated children following OLT and identify risk factors. The medical charts of all patients who underwent OLT at our institution were reviewed. Between 1985 and 2010, 218 OLTs were performed on 188 pediatric recipients, of which 154 were included in the study. Three patients (3%) of the 102 receiving CsA developed FA, compared with nine (17%) in the 52 tacrolimus-treated patients, the latter exceeding general population reported FA prevalence (RR 5.88; 95% CI: 1.66-20.81). All TAFA cases underwent transplantation before the age of three with an incidence of 29% (9/31) in the tacrolimus-treated children in comparison with 7% (3/41) in the CsA group (RR 3.97; 95% CI: 1.17-13.45). Eosinophilia was present in 81% of children receiving tacrolimus compared with 54% in the CsA group (p = 0.002). We observed a statistically significant increase incidence of FA in tacrolimus-treated children following an OLT and those under the age of three are particularly vulnerable. The underlying process is still unknown and probably multifactorial.

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Background IL-15 is involved in the development and homeostasis of CD8 lymphocytes, NK and iNKT cells, and intraepithelial lymphocytes. It also promotes migration, proliferation and survival of mast cells. Its receptor on lymphocytes is a heterotrimeric complex which shares the IL2-Rb and common gamma ( gc ) chains. IL-15-mediated signaling in mast cells might make use of an alternative receptor provisionally designated as IL-15RX. In a murine model, gc-dependent signaling was shown to be essential for IL4– and IL-9–induced proliferation and survival of mast cells, but not IL-15 even in the wild-type mouse.

1601 Background: The prognosis of follicular lymphoma (FL) remains a challenge despite stratification on the FLIPI scoring, histological grading, and microenvironement cell type infiltration. Thus, new biomarkers are needed to identify patients (pts) who require a more aggressive therapeutic strategy or targeted therapies. Transferrin receptor (TfR) is highly expressed in proliferating cells including non Hodgkin lymphoma cells. High TfR level has been associated with disease progression in chronic lymphocytic leukaemia and is observed at relapse in mantle cell lymphoma. Murine anti human TfR (CD71) antibody has been validated for histological and flow cytometric evaluation of TfR expression. The aim of this work was to assess expression and prognosis value of TfR expression on FL cells. Material and Methods: We retrospectively analyzed the expression level of CD71 in neoplastic B cells of FL lymph node biopsies at diagnosis of 45 pts who received first-line treatment with Rituximab and anthracyclines based chemotherapy at the hematology department of Necker Hospital, Paris, France, and assessed its prognosis value (second treatment free survival (TFS) and overall survival (OS)). High CD71 and Ki67 expression in FL lymph nodes biopsies were defined as upper than 25% of FL cells. CD71 expression was compared with FLIPI at diagnosis and the expression and prognosis value of Ki67 expression. Results: Characteristics of the cohort are shown in [table 1][1]. FLIPI risk was low in 7 pts (16%), intermediate in 19 (43%) and high in 18 (41%). FLIPI stratification did not show correlation with both OS and TFS in this small cohort of pts. Among 44 evaluable pts, CD71 expression was heterogeneous ranging from 0% to 90% of FL cells. T cell labeling was used as a quality control. CD71 low expression (225% of tumor cells) was observed in 31 samples (69%) and KI67 low expression in 27 (60%). After a median follow-up of 40 months (range 1 – 94) for the all cohort, TFS was 68.9 % (95 % CI 0.55–0.82) and OS was 91.1% (95% CI 0.83 – 0.99). The mean TFS after R-chemotherapy was 86 months in the low CD71 level group vs. 18 months in the high CD71 level group (p=0,075). The mean estimated OS after first R-chemotherapy was 89 months in the low CD71 group vs. 54 months in the high CD71 group (p=0,006) ([figure 1][2]). By univariate analysis, high Ki67 expression was associated with significant lower OS (p=0.035) but not TFS (p=0,162). In multivariate analysis including CD71 level, FLIPI risk, FLIPI parameter groups, CD71 was the only factor independently associated with OS (p=0,019) and TFS (p=0,037). Furthermore, Cox regression analysis did not reveal any significant correlation between Ki67 and TFS or survival. Conclusion: CD71 expression is an important independent histological prognostic factor in this monocentric retrospective study predicting OS in FL patients after first-line treatment with R anthracyclin based regimen. Ki 67 was also associated with OS in univariate analysis, but CD71 was the only independent factor associated with OS and TFS in multivariate analysis. These promising results warrant further studies in a larger prospective cohort and provide a rationale to target Tfr in relapsing refractory FL. ![Figure 1:][3] Figure 1: Overall survival (OS) after first line R anthracycline therapy according to the CD71 high and low risk groups | Characteristics | CD71 low | CD71 high | p. | |:--------------------------------------:| ---------------- | ------------- | ----- | | n (%) | 31 (69%) | 14 (31%) | | | At Diagnosis | | Age | | | | | < 60 ans | 19 | 3 | 0,045 | | 3 60 ans | 12 | 10 | | | Sex | | | | | Male | 16 | 7 | 1 | | Female | 15 | 7 | | | Clinical stage | | | | | I-II | 4 | 1 | 1 | | III-IV | 27 | 13 | | | BM involvement | | | | | Yes | 22 | 7 | 0,173 | | No | 9 | 7 | | | No. of involved nodes area (FLIPI) | | | | | 24 | 15 | 4 | 0,335 | | >4 | 16 | 9 | | | LDH | | | | | N | 22 | 12 | 0,313 | | > N | 9 | 2 | | | Hemoglobin | | | | | 3 12 g/dl | 1 | 2 | 0,204 | | < 12 g/dl | | | | | FLIPI risk group | | | | | Low | 6 | 1 | 0,251 | | Intermediate | 15 | 4 | | | High | 10 | 8 | | | Ki67 expression | | | | | Low (225%) | 23 | 8 | 0,007 | | High (>25%) | 4 | 10 | | | After treatment | | Median FU (months) | 47.8 [10.5-92.5] | 30 [1.1-75.1] | | | Need second line of treatment: No. (%) | 10 (32) | 7 (50) | ns | | Deceased: No. (%) | 1 (3) | 4 (29) | 0.03 | Table 1. Characteristics of the pts at baseline and evolution after first line R-CHOP like regimen according to the CD71 risk groups Disclosures: No relevant conflicts of interest to declare. [1]: #T1 [2]: #F1 [3]: pending:yes

Abstract 1057 Background: Primary immunodeficiencies (PID) are rare congenital disorders involving defects of the immune system. Aside from infectious complications, patients are at increased risk of malignant complications, which represent a leading cause of mortality in this context. The pathophysiology underlying malignant complications, especially lymphoid malignancies, in PID is not fully understood. The molecular mechansims of PID, that often involve lymphoid developent pathways, may also play a role in oncogenesis. A better understanding of the epidemiology of malignancies in PID may provide important insights in oncogenesis, particularly in lympomagenesis. Material and methods: French National Reference Center for Primary Immune Deficiencies (CEREDIH) has registered 4632 patients with PID as of July 2012. T-cell immunoficiencies and B-cell immodificencies reprensent 35.8% and 46.1% respectively. Patients with Ataxia-Telangiectasia and Severe Congenital Neutropenia were excluded frome the present analysis as they represent a more homogeneous group in terms of molecular pathophysiology and have been described elsewhere. T-cell immunodeficiencies comprise Severe combined immudoficiencies, Combined immunodeficiencies, other well defined T-cell immunoficiencies (including Wiskott-Aldrich Syndrome), and diseases of immune regulation (including X-linked lymphoproliferative disease and Autoimmune lymphoproliferative syndrome). B-cell immunodeficiencies include Agammaglobulinemia, Common Variable Immunodeficiency, Unspecified primary hypogammaglobulinemia, Selective IgA deficiency, Hyper-IgM symdrome and IgG subclass deficiency. Diagnostic class of PID, Age at diagnosis of PID, age at diagnosis of neoplastic complication, type of neoplasia, and survival were retrospectively colloected from the medical files. Non-melanomatous skin cancers and lymphoproliferative disorders occuring after allogeneic stem cell tranplantation were excluded from the analysis. Results: 4632 patients with PID were analyzed. Two hundred and sixty seven patients developed 276 cancers (incidence 5.8%). One hundred and fifty seven patients developed lymphoid malignancies and 78 patients developed solid tumors (56.4% vs. 28.3% respectively). Compared to patients with B-cell PID, patients with T-cell PID had lower age at diagnosis of PID (5.5 [0–12.4] vs. 1.3–78]). Lymphoid malignancies, mainly high grade lymphomas were more prevalent in T-cell PID and PID diagnosed at a younger age (median age at diagnosis of PID for patients with lymphoid malignancies vs. solid tumors, 5.2 yr [0–85] and 37.5 [0–80] respectively, p Discussion: PID bear a high risk of malignancies (5.8%). Solid tumors are observed mainly in B-cell PID and are diagnosed at an older age. Lymphoid malignancies are observed mainly in T-cell PID and B-cell PID diagnosed at a younger age, underlying a possible pathophysiological link between T-cell PID and a subset of B-cell PID. Disclosures: No relevant conflicts of interest to declare.