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CAR-T CELLS RADICALLY MODIFY THE MANAGEMENT OF RELAPSED/REFRACTORY PRIMARY CEREBRAL LYMPHOMAS. We present here the real-life results of the use of commercial CAR-T cells in PCNSL with a prolonged follow up and compare them to the results of patients in the LOC network who did not benefit from them. B Methods: b We retrospectively selected from the French LOC network database the PCNSL patients treated with CAR-T cells from the 3rd line of treatment. [Extracted from the article]

Patients with autoimmune hemolytic anemia (AIHA) may require intensive care unit (ICU) admission. In order to describe the characteristics of AIHA patients in ICU and identify prognosis factors, clinical and biological data from 44 patients admitted in one ICU between 2002 and 2015 were retrospectively analyzed. The main reasons for ICU admission were profound anemia without any organ failure in 19 patients (either for safer transfusion or continuous monitoring only). Twenty-five (57%) patients had a past history of hemopathy. Twenty patients presented with a direct anti-globulin test (DAT) positive for immunoglobulin G (DAT-IgG) only (46%), 8 with a DAT positive for both IgG and complement (DAT-IgG+C) (36%), and 16 with a DAT positive for complement only (DAT-IgG+C) (18%). Corticosteroids and rituximab were administered to respectively 44 (100%) and 12 (25%) patients. Red blood cell transfusion was required in 28 (64%) patients. Ten (23%) patients received vasopressors. Renal replacement therapy was necessary in 14 (31.8%) patients. Thirteen (30%) patients died in the ICU. There was no difference between survivors and non-survivors regarding associated comorbidities like hemopathy (18/31 [58%] vs. 7/13 [54%], p = 0.80). In decedents, age was higher (72 years [57.8-76.3] vs. 50 years [34.3-64], p < 0.01) and organ dysfunctions were more severe at day 1 (SOFA 8 [7-11] vs. 5.5 [3-7], p < 0.01). Patients with a DAT-IgG displayed poorer outcome in comparison with patients with DAT-IgG+C/C (hospital mortality 69% vs. 36%, p = 0.04). Mortality rate of AIHA patients requiring ICU admission is consequential and appears to be impacted by age, organ failures, and DAT-IgG. [ABSTRACT FROM AUTHOR]

Objectives Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. Methods Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). Results 166 SLE patients’ data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval −472 to −260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). Conclusions No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE. [ABSTRACT FROM AUTHOR]

Objective Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. Methods We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. Results To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index ( P = 0.008), no treatment with corticosteroids ( P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations ( P = 0.017), low platelet count ( P < 0.001), low neutrophil count ( P < 0.001), and high estimated creatinine clearance ( P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) ( P < 0.001). Conclusion We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians. [ABSTRACT FROM AUTHOR]

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Eighteen cases of human herpesvirus 8 (HHV-8)–related Castleman Disease in the absence of human immunodeficiency virus (HIV) infection are reported. Their clinical, laboratory and pathological features are similar to those described in HIV-positive cases. HHV-8 related Castleman Disease might be considered a single clinicopathologic entity whatever the HIV status.Background. Castleman disease (CD) in the context of human immunodeficiency virus (HIV) infection is well described. It is almost always multicentric (MCD) and linked to human herpesvirus 8 (HHV-8). There are limited published data surrounding HHV-8–related CD among HIV-negative patients.Methods. From January 1995 through June 2012, we identified in a single center 18 HIV-seronegative patients with HHV-8–related CD. We report on their clinical, pathological, and laboratory features.Results. All cases were multicentric. Patients were aged 42–83 years and were referred with a relapsing remitting syndrome of fever (94%), constitutional symptoms (100%), peripheral lymphadenopathy (100%), splenomegaly (72%), hepatomegaly (50%), and edema (28%). Kaposi sarcoma was observed in 9 cases. Anemia and serum markers of inflammation were present in all cases. Polymerase chain reaction for HHV-8 DNA was positive on blood samples in all cases, whereas only 12 of 16 patients tested had positive HHV-8 serology at diagnosis. All cases showed the classic histological features of MCD, and LANA-1 immunostaining identified HHV-8–infected plasmablasts in 16 of 16 tested cases. Reactive hemophagocytic syndrome (44%), autoimmune hemolytic anemia (33%), and lymphoma (22%) were the commonest associated complications. Remission was obtained with etoposide in 13 of 15 cases. Rituximab allowed prolonged remission off therapy in 10 cases. Death occurred in 3 patients not treated with rituximab. These features were similar to those described in HIV-positive HHV-8–related MCD. Comparison between these 18 cases and 12 HIV-negative HHV-8–unrelated MCD cases showed marked discrepancies.Conclusions. HHV-8–associated MCD may be considered as a single clinicopathological entity regardless of HIV status. [ABSTRACT FROM PUBLISHER]

Treatment of common variable immunodeficiency disorders ( CVID) is based on replacement therapy using intravenous (i.v.) or subcutaneous (s.c.) immunoglobulin ( Ig)G. Interindividual variation of IgG dose is common. A total of 380 CVID patients on stable IgG replacement from two prospective cohorts were analysed. An 'efficiency' index was defined as the ratio of serum IgG trough level minus IgG residual to the average weekly dose of IgG infusion. A reduced efficiency of IgG was associated independently with the i.v. route ( P < 0·001) and with the presence of at least one CVID disease-related phenotype (lymphoproliferation, autoimmune cytopenia or enteropathy) ( P < 0·001). High IgG efficiency was noted in patients homozygotes for the variable number tandem repeat ( VNTR) 3/3 polymorphism of the neonatal Fc receptor gene [IgG Fc fragment receptor transporter alpha chain ( FCGRT)] promoter, and this was particularly significant in patients treated with IVIG ( P < 0.01). In a multivariate analysis, FCGRT VNTR 3/3 genotype ( P = 0·008) and high serum albumin ( P < 0·001) were associated independently with increased efficiency of i.v. Ig. [ABSTRACT FROM AUTHOR]

Background Cutaneous involvement has been reported in 30–40% of children with the familial form of haemophagocytic syndrome. However, few studies have focused on cutaneous manifestations in patients with reactive haemophagocytic syndrome (RHS). Objectives To describe the frequency, clinical features and prognosis of skin involvement in adult patients with RHS. Methods We conducted a retrospective study in a French university-based tertiary centre. The medical records of all adult patients with a suspected or confirmed diagnosis of RHS during a 2-year period were reviewed. Demographic, clinical, biological and histological data of patients were compared using nonparametric tests. Results The medical charts of 151 patients were reviewed, 69 of whom had a definite diagnosis of RHS (35% women; mean ± SD age 49 ± 17 years). The aetiology of RHS was mainly B-cell or T-cell lymphoma ( n = 33) or herpesvirus infection ( n = 19). Cutaneous manifestations were observed in 32 (46%) patients and were of three types: (i) specific to the underlying malignancy (Kaposi sarcoma n = 8, cutaneous lymphoma n = 4), (ii) reflecting the biological consequences of RHS (thrombopenic purpura n = 10, conjunctival jaundice n = 7), and (iii) a generalized, transient, nonpruriginous maculopapular rash ( n = 18). None presented with erythroderma, or with eczematiform, ichthyosiform, psoriasiform or bullous lesions. One patient had cytophagic histiocytic panniculitis. Histological features of maculopapular rash biopsies were usually nonspecific. The rate of in-hospital death was not significantly associated with cutaneous involvement. Conclusions A generalized, nonpruriginous, transient, maculopapular rash is frequently observed in patients with RHS. Although nonspecific, awareness of this cutaneous involvement may assist physicians in the initial diagnosis of RHS. [ABSTRACT FROM AUTHOR]

The article discusses the rare occurrence of disseminated skin involvement in patients with HIV-associated Burkitt lymphoma (BL). Topics discussed include the histopathological, clinical and cytogenetic features of skin involvement in BL associated with HIV, the histopathological differential diagnosis of BL, and the poor short-term prognosis in the patients.

This study aims to describe [18]F-fluorodeoxyglucose ([18]F-FDG) positron emission tomography/computed tomography (PET/CT) findings in patients with AIDS-related Burkitt lymphoma, at various times of treatment, and to define its utility for a better patient management. We retrospectively studied 13 consecutive HIV-positive patients with Burkitt lymphoma who underwent one or more PET/CT. In 5 of 5 patients imaged before treatment, PET/CT confirmed all involved sites detected at conventional work-up and demonstrated additional sites in 4 of 5 patients. Lymph node involvement, which is known to be uncommon in endemic or sporadic Burkitt lymphoma, was present in 54% of patients. Additionally, in 3 patients, Burkitt lymphoma was predominantly located in parotid lymph nodes, which is also an unusual finding. A negative scan was encountered in 3 of 10 patients imaged during treatment and in 1 of 4 patients imaged after treatment completion and was always associated with lasting complete remission. Presence of residual area of uptake was related to both favorable and unfavorable outcome whether performed during treatment (5/7 and 2/7, respectively) or after (1/3 and 2/3, respectively). Areas of increased uptake could be observed in lung (4 cases) or esophagus (3 cases), and were clinically related to pneumonia or esophagitis. We recommend PET/CT for accurate initial staging of patients with AIDS-related Burkitt lymphoma. PET/CT is also useful to monitor treatment response, as regression of initial disease can be early observed. Furthermore, PET/CT appears to have prognostic value, as a negative scan was always associated with a favorable outcome. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) infection is a risk factor for thrombotic microangiopathy (TMA). We sought whether a severe deficiency in ADAMTS13, the enzyme specifically involved in the cleavage of von Willebrand factor, was associated with specific presenting features and outcome in HIV-associated TMA. In this prospective, multicentre, case–control study, 29 patients of 236 in the French Network on TMA had an HIV-associated TMA. Seventeen patients with severe ADAMTS13 deficiency (ADAMTS13 <5% HIV+ group) were compared to 12 patients with a detectable ADAMTS13 activity (ADAMTS13 ≥5% HIV+ group). HIV+ patients were also compared to 62 patients with idiopathic TMA, either with (45 patients, ADAMTS13 <5% idiopathic group) or without (17 patients, ADAMTS13 ≥5% idiopathic group) severe ADAMTS13 deficiency. ADAMTS13 <5% HIV+ patients had less AIDS-related complications than ADAMTS13 ≥5% HIV+ patients (23.5% versus 91.6%, respectively, P = 0.0005) and their median CD4+ T cell count was higher ( P = 0.05). TMA-associated death rate was higher in ADAMTS13 ≥5% HIV+ patients than in ADAMTS13 <5% HIV+ patients (50% versus 11.7%, respectively, P = 0.04). In ADAMTS13 <5% patients, TMA-associated death rate was comparable between HIV+ and idiopathic patients (15.5% in idiopathic patients, P-value was non-significant). By contrast, TMA-associated death rate in ADAMTS13 ≥5% HIV+ patients was higher than in idiopathic patients (11.7% in idiopathic patients, P = 0.04). In conclusion, HIV-associated TMA with severe ADAMTS13 deficiency have less AIDS-related complications and a higher CD4+ T cell count. TMA prognosis is better and comparable to this of idiopathic forms. [ABSTRACT FROM AUTHOR]

Cryopreservation and thawing of haematopoietic stem cells are associated with cell loss and infusion-related toxicities. We analysed viability, total nucleated cell (TNC) and CD34+ cell recovery, and infusion-related toxicities of 952 thawed and washed products. Mean TNC and CD34+ viable cells recoveries were 55.9±18.6 and 98.0±36.5%, respectively. Mean cell viability was 68.25±18.9%. TNC recovery was correlated with viability but independent of the initial nucleated cell concentration. No difference in TNC recovery or viability was observed according to underlying diseases, except for myeloma, for which these variables were significantly lower (P<0.05). CD34+ cell recovery was not correlated with viability or CD34+ initial count and was similar for all diseases. Cryostorage duration was not associated with cell loss. Immediate adverse events occurred in 169 patients (19%) and were moderate (grade I or II) for the majority of patients. Clinical toxicity was associated with a higher infused cell number and the presence of clumps in infused bags. The washing procedure of cell products lead to a low rate of adverse events, but patients transplanted with high cell numbers or bags in which clumps were identified are predisposed to such complications.Bone Marrow Transplantation (2007) 40, 831–835; doi:10.1038/sj.bmt.1705830; published online 27 August 2007 [ABSTRACT FROM AUTHOR]

Background. Kaposi sarcoma (KS) occurs mainly in immunocompromised patients and is strongly associated with infection with human herpesvirus 8 (HHV-8; also known as 'KS-associated herpesvirus'). We hypothesized that KS is linked to deficiencies in specific anti-HHV-8 T cell immunity. Methods. We studied asymptomatic HHV-8 carriers coinfected with human immunodeficiency virus (HIV; n=23) and patients with HIV-related or classic KS (n=29). We used an interferon-gamma enzyme-linked immunospot assay with 56 specific peptides distributed on 6 HHV-8 proteins (glycoprotein [gp] B, gpH, gp35/37, latent nuclear antigen 1 [LANA-1], K12, and K15) to detect HHV-8-specific T cell responses. Results. We found that patients with KS responded to these peptides less often and had much lower HHV-8-specific T cells counts than did asymptomatic HHV-8 carriers (P=.001 and P=.0004, respectively), regardless of CD4 T cell count or HHV-8 load. The frequency of Epstein-Barr virus-specific T cells was similar in both groups. Conclusions. Our results suggest that HIV-related and classic KS are associated with a lack of HHV-8-specific T cells. Also, we have described 8 new HHV-8 T cell epitopes in LANA-1, K12, and K15, including 2 CD4 T cell epitopes. These data provide new insight into HHV-8 cellular immunity. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

In order to assess the prognostic value of inhibitory anti-ADAMTS13 antibodies in thrombotic thrombocytopenic purpura (TTP), we performed a multicentre prospective study of 33 adult patients with idiopathic acquired TTP. Patients were treated with high-dose plasma infusion and therapeutic plasma exchange. Patients without (group 1, n = 12) and with (group 2, n = 21) detectable inhibitory anti-ADAMTS13 antibodies were compared for clinical presentation, treatment and outcome. Both groups were comparable for clinical presentation. All patients in group 1 achieved a sustained complete remission within a median of 7 d [95% confidence interval (CI), 4–18], which required a median plasma volume of 235 ml/kg (range, 131–1251). In group 2, 17 patients achieved a durable complete remission within a median of 23 d (95% CI, 11–32) ( P = 0·001). Median plasma volume was 718 ml/kg (range, 219–3107) ( P = 0·02). In group 2, there was a trend for more episodes of flare-up than in group 1 (13 vs. 3, respectively, P = 0·07). Four patients, all from group 2, died ( P = not significant). The relapse rate was comparable between both groups. We suggest that TTP with detectable inhibitory anti-ADAMTS13 antibodies displays a worse prognosis, relative to a delayed platelet count recovery, a higher plasma volume requirement to achieve complete remission, and a trend for more frequent episodes of flare-up. [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency (CVID) is a very heterogeneous syndrome defined by impaired immunoglobulin production. The functional classification of CVID patients on the basis of in vitro immunoglobulin production is time consuming and has never shown any predictive value. We propose a classification based on the quantitative repartition of naive/memory B cells according to the dual expression of IgD and CD27. Fifty-seven patients were categorized into three groups: Group MB2 (11 patients, 19%) with normal memory B cells; Group MB 1 (19 patients, 33%) with defective switched memory (IgD[SUP-]CD27[SUP+]) but normal nonswitched memory B cells (IgD[SUP+]CD27[SUP+]); Group MB0 (27 patients, 47%) with almost no memory B cells. In addition, a downexpression of activation markers (CD25, CD21, CD80, CD86) on B cells characterized the group MB1 patients and was associated with an upexpression of activation markers (HLA-DR, CD95, CD57) on T cells. This classification correlates with some clinical aspects showing a higher prevalence of splenomegaly (16/27, 59%), lymphoid proliferation (13/27, 48%) and granulomatous disease (12/27, 44%) in group MB0. Splenomegaly was also frequent in group MB1 (8/19, 42%). In contrast, autoimmunity was observed with similar prevalence in all three groups. Moreover, by analyzing B cell phenotype, immunoglobulin transcript expression, and somatic mutations, we propose different putative mechanisms responsible for impaired B cell activation and memory differentiation in this syndrome. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed 5 cases of hemophagocytic lymphohistiocytosis (HL) associated with human her-pesvirus 8 (HHV-8) reactivation in human immunodeficiency virus (HIV)-infected patients. All patients had clinical and biological features characteristic of HL. Pulmonary symptoms were present in all patients and were frequently life threatening. The mean number of HL episodes was 6. Four patients had HL-associated Kaposi sarcoma, and 3 had multicentric Castleman disease. The mean CD4 cell count was 200 cells/mm(3). HIV loads were stable in all patients. All patients had high levels of HHV-8 in peripheral blood mononuclear cells during attacks, and a significant increase in this parameter before the attacks was seen in 3 patients. Although 2 patients died of HL, 3 are still alive and receiving etoposide therapy (mean follow-up, 3 years). HHV-8-related HL is associated with life-threatening symptoms and biological HHV-8 reactivation, and it may be controlled in the long term by etoposide therapy combined with highly active antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Kikuchi–Fujimoto disease is a rare systemic disease with uncommon neurological involvement. We report the case of a 30-year-old Asian woman who presented a rapidly progressive loss of vision. Magnetic resonance imaging (MRI) of the optic nerve revealed an inflammation of the left optic nerve with chiasmatic involvement, without any encephalic or medullar lesion. Thoracic computed tomography scan showed bilateral axillary lymphadenopathy. Analysis of a biopsy of the axillary lymph node showed typical histological findings of Kikuchi–Fujimoto disease. There was no clinical or biological sign of associated systemic lupus erythematosus. The patient spontaneously recovered normal visual acuity in 4 weeks, with resolution of MRI abnormalities. No optic neuritis relapse or neurological event occurred in a 3-year follow-up. To our knowledge this is the first case of optic neuritis associated with Kikuchi–Fujimoto disease. [ABSTRACT FROM AUTHOR]

A response by G. Le Guenno, L. Galicier, and C. Fieschi to a letter to the editor about sinus histiocytosis with massive lymphadenopathy (SHML) is presented.

We report the case of a 30-year-old HIV-infected man admitted for a meningeal syndrome and a zoster rash. The CSF had cytological features suggesting a primary CNS lymphoma (PCNSL). The large lymphoid cells had a fine chromatin with nucleoli, a basophilic cytoplasm with azurophilic granules and high mitotic activity. Several arguments demonstrated the viral origin of the meningitis: the large lymphoid cells were of T origin with no evidence of clonal TCR γ gene rearrangement. The PCR was positive for Varicella-Zoster Virus (VZV) and EBV DNA. Clinical evolution was favorable under acyclovir. We should be cautious in the differential diagnosis between viral meningitis and PCNSL. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 29-year-old woman with T-cell lymphoma who was referred for epidermodysplasia verruciformis (EV) associated to warts hands, wrists and feet. It highlights the presence of Tinea versicolor-lesions on forehead and neck. It also informs that her immunoglobulin levels were low causing recurrent respiratory tract infections and resulting in bronchiectasis and emphysema.

The article presents a case study of a 67-year-old woman with paraneoplastic dermatomyositis (DM) developing diffuse alveolar haemorrhage (DAH). She received high-dose steroids and prednisone and intravenous cyclophosphamide pulses. In three weeks of treatment, her respiratory function improved, skin rash vanished, and muscle strength was restored. It describes the successful treatment of diffuse alveolar haemorrhage (DAH) occurrence in the course of dermatomyositis (DM).

A response by Alexandre Le Joncour, F. Bidegain and B. Nebbad to letters to the editor about their article "Hemophagocytic lymphohistiocytosis associated with Bartonella henselae infection in an HIV-infected patient" in a 2016 issue is presented.