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Primary effusion lymphoma (PEL) is a rare B‐cell non‐Hodgkin lymphoma associated with Kaposi Sarcoma‐associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein‐Barr virus (EBV) in 60−80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow‐Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations. [ABSTRACT FROM AUTHOR]

Summary: Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD‐PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow‐up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD‐PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain‐of‐function p.N666S variant in two. Interestingly, both patients had hyaline‐vascular UCD subtype, were in the UCD‐PNP subgroup and had FDCS. Sera from 25 UCD‐PNP patients and 6 PNP patients without UCD were tested for PNP‐associated autoantibodies. Sera from UCD‐PNP patients had a strong reactivity against the N‐terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD‐PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history. [ABSTRACT FROM AUTHOR]

Survivors of immune‐mediated thrombotic thrombocytopenic purpura (iTTP) are exposed to clinical relapses when a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13 (ADAMTS13) activity decreases during follow‐up. Although preemptive rituximab usually improves ADAMTS13 activity in this context, 15% of patients experience refractoriness or intolerance to rituximab and require alternative strategies. Here, we addressed whether cyclosporine A (CSA) could improve ADAMTS13 activity and prevent clinical relapses in this context. We treated preemptively with CSA 14 iTTP patients who were unresponsive (n = 11) or intolerant (n = 3) to rituximab. All patients had a severe ADAMTS13 deficiency (activity <20%) and otherwise in clinical remission. ADAMTS13 activity normalized in almost all patients (n = 13, 93%), after a median time of 2.5 months [IQR 1–6] following initiation. Median duration of CSA treatment was 17.5 months [IQR 10–34]. ADAMTS13 activity further declined to undetectable values during follow‐up in five patients, but retreatment with rituximab or CSA allowed a recovery in ADAMTS13 activity in three cases. CSA could be stopped durably in two patients, while two others experienced an ADAMTS13 relapse. Severe but reversible side effects requiring cessation of the treatment occurred in two patients. CSA provides high and sustained response rates in patients who are refractory or intolerant to rituximab, with acceptable adverse events. [ABSTRACT FROM AUTHOR]

Summary: Hepatic dysfunction (HD) is common in patients with haematological malignancies. Hepatic haemophagocytosis (HH) was detected in >50% of liver biopsies taken when HD remained unresolved after standard examination. We aimed to explore the contribution of liver biopsy in patients with both haematological malignancies and HD, describe the population of patients with HH, assess the prognostic impact of HH, and investigate haemophagocytic syndrome diagnostic score (HScore) utility in patients with HH. Between 2016 and 2019, 116 consecutive liver biopsies (76 transjugular, 40 percutaneous) were taken in 110 patients with haematological malignancy and HD (hyperbilirubinaemia, elevated transaminases, and/or cholestasis) and without a clear diagnosis. Liver biopsies were safe and diagnostically efficient. Predominant diagnoses included: HH (56%), graft‐versus‐host disease (55%), associated infections (24%), sinusoidal obstruction syndrome (15%), and tumoral infiltration (8%). Of patients, 35% were critically ill and 74% were allogeneic haematopoietic stem cell transplantation recipients, while 1‐year overall survival (OS) was 35% with HH versus 58% without HH (p = 0.026). The 1‐year OS was 24% with a HScore of ≥169 versus 50% with a HScore of <169 (p = 0.019). Liver biopsies are feasible in and contribute significantly to haematology patients with HD. HH occurred frequently and was associated with a poor prognosis. Combined with liver biopsy, the HScore may be helpful in refining haemophagocytic syndrome diagnosis. [ABSTRACT FROM AUTHOR]

Summary: Idiopathic multicentric Castleman disease (iMCD) is a non‐clonal inflammatory lymphoproliferative disorder of unknown origin. Recently, TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis and organomegaly) emerged as a singular variant of iMCD in Asia and was associated with a severe course and a poor outcome. The present study describes the first large Western cohort of TAFRO syndrome patients (n = 25) meeting the All Japan TAFRO Syndrome Research Group diagnostic criteria. Characteristics of TAFRO patients were compared to iMCD‐not otherwise specified (iMCD‐NOS) patients used as a control group (n = 43). Our results show that despite baseline characteristics in accordance with previously reported series, Western TAFRO syndrome patients do not appear to present with a worse outcome than iMCD‐NOS patients. There were no significant differences between the two groups regarding treatment choice, response to rituximab (71% vs. 67%) or tocilizumab (69% vs. 91%) in TAFRO and iMCD‐NOS, respectively. The two‐year overall survival was above 95% in both groups. Limits of inclusion and exclusion criteria for TAFRO definition are also discussed. Our findings raise the question of the singularity of the TAFRO entity in Western countries. The data should promote further research using unsupervised models to identify markers of disease severity in Western cohorts of iMCD patients. [ABSTRACT FROM AUTHOR]

The proportion of HIV-infected patients aged >=65 years is projected to nearly triple between 2010 to 2030, from 8.5% to 21.4% in Western countries.7 The number of patients enrolled in the HIV-lymphoma cohort was relative stable over time, with an increased incidence rate of MCL during recent years as half of the cases were diagnosed in the past 4 years. This result should be interpreted with caution due to the small number of patients and the context of COVID-19 pandemic and should not prevent treating these patients according to the current guidelines with up-front ASCT when feasible and rituximab maintenance therapy. Mantle cell lymphoma (MCL) is a rare subtype of lymphoid malignancy, representing 5%-7% of adult-onset non-Hodgkin lymphoma (NHL) in Western countries, but with a rising incidence.1 Most patients with MCL have an aggressive disease. [Extracted from the article]

Reactive hemophagocytic lymphohistiocytosis (rHLH) management requires early recognition, trigger identification, and adequate treatment in order to reduce mortality. We assessed the diagnostic yield of tissue biopsies to identify trigger in severe rHLH. We included all consecutive patients presenting an rHLH diagnosis (HLH‐2004 criteria) admitted to the intensive care unit (ICU) of a tertiary hospital. This retrospective diagnostic accuracy study was conducted according to the Standards for Reporting Diagnostic Accuracy Statement. Among the 134 included patients (median age 47 years [IQR 47–56]), an underlying immunodeficiency was previously known in 61.2%. rHLH trigger was identified in 127 patients (94.8%) (hematological disorder 75%, infection 16%, systemic disease 4%). Diagnostic yield of tissue biopsies was as follows: lymph node 75% (95% confidence interval [CI], 61–85), skin 50% (95% CI, 27–73), bone marrow 44% (95% CI, 34–55), liver 30% (95% CI, 15–49). Splenectomy (yield 77%; 95% CI, 46–95) was reserved to cases of diagnostic deadlock. Procedural severe adverse events included two cases of reversible hemorrhagic shock. Seventy‐eight percent of patients received etoposide regarding to the rHLH severity, and 68% could receive trigger‐specific treatment in the ICU. A comprehensive diagnostic workup led to an rHLH trigger identification in 95% of patients, allowing prompt initiation of appropriate therapy. Prospective studies to validate a standardized diagnostic approach are warranted. [ABSTRACT FROM AUTHOR]

Intensive rituximab regimen in immune-mediated thrombotic thrombocytopenic purpura can circumvent unresponsiveness to standard rituximab treatment We focused on iTTP patients in clinical remission who failed to display improved ADAMTS13 activity following a standard treatment with rituximab.3 Patients were enrolled prospectively in our registry from January 2012 to July 2018 through the French Reference Center for Thrombotic Microangiopathies network (www.cnr-mat.fr). We report that an intensive rituximab regimen inspired by maintenance regimens of low-grade B-cell lymphomas allows improving ADAMTS13 activity in most cases (>75% of formerly unresponsive patients), with an acceptable safety profile. So far, only single cases previously supported the relevance of this strategy.10,11,12 Of interest, all three patients who did not respond to intensive therapy received a regimen consisting in a twice-a-year infusion of rituximab instead of the two- to three-month infusion regimen typically offered to the other patients. [Extracted from the article]

We describe a unique case of human T‐lymphotropic virus 1 (HTLV‐1)‐associated infective dermatitis‐like lesions in systemic lupus erythematosus. This suggests that some lupus patients may have immunological abnormalities resembling to those described in chronic HTLV‐1 infection. [ABSTRACT FROM AUTHOR]

Summary: We report the off‐label use of bortezomib combined with dexamethasone in eight adults with severe and multi‐refractory warm auto‐immune haemolytic anaemia (wAIHA). After six cycles of induction therapy, 6 of the 8 patients achieved response (3 complete response, 3 response). Response was obtained after a median of 2 (1–4) cycles. After a median follow‐up of 14 (6–36) months, six patients maintained a response (bortezomib/dexamethasone maintenance, n = 4); five patients experienced at least one moderate adverse event, including peripheral neuropathy (n = 2). These results suggest that bortezomib/dexamethasone combination is a promising approach with acceptable toxicity for treating severe refractory wAIHA in adults. [ABSTRACT FROM AUTHOR]

Summary: We retrospectively analysed 71 cases of Unicentric Castleman disease, a rare, usually asymptomatic, benign lymphoproliferative disorder presenting as a unique nodal mass. Although surgery is considered as the gold standard therapy, only 38 patients (54%) underwent initial surgical resection and 95% were cured. An additional 9 patients had surgery after an attempt at medical reduction. Reduction therapy was used in 21 patients with a 55% response rate, but without evidence for an optimal regimen. Radiotherapy was limited to 8 patients because of associated toxicity. Watch and wait was considered in 13 asymptomatic patients and 11 of these remained stable for up to 17 years. [ABSTRACT FROM AUTHOR]

Objective: Angioimmunoblastic T‐cell lymphoma (AITL) is frequently associated with autoimmune cytopenia (AIC). Whether such patients have a particular phenotype and require particular management is unclear. Method: Angioimmunoblastic T‐cell lymphoma patients from the multicentric database of the Lymphoma Study Association presenting with AIC during disease course were included and matched to AITL patients without AIC (1/5 ratio). Results: At diagnosis, AIC patients (n = 28) had more spleen and bone marrow involvement (54% vs 19% and 71% vs 34%, P < 0.001), Epstein‐Barr virus replication (89% vs 39%, P < 0.001), gamma globulin titers (median 23 vs 15 g/L, P = 0.002), and proliferating B cells and plasmablasts in biopsies, as compared to control patients (n = 136). The 28 AIC patients had 41 episodes of AIC, diagnosed concomitantly with AITL in 23 (82%) cases. After a median follow‐up of 24 months (range 3‐155), 10 patients relapsed, all associated with AITL relapse. Conclusion: Our results provide new insight into AIC associated with AITL by highlighting the significant interplay between AITL and B‐cell activation leading to subsequent autoimmunity. [ABSTRACT FROM AUTHOR]

Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy (TMA) syndrome (Kremer et al. [8]). These three cases of TTP occurred during lenalidomide therapy (Table)- there was nothing that can usually be associated with thrombotic microangiopathy - no infectious trigger, no association with other autoimmune disorders, and no drugs intake. For our patients, the presence of anti-ADAMTS13 antibodies in each case and the efficacy of TPE and/or rituximab therapies imply an immune-mediated reaction. Montefusco et al. ([10]) described six autoimmune diseases after lenalidomide administration to 140 patients (4-3%): three autoimmune cytopenias and three organ-specific autoimmune disorders, occurring mostly in the first months of treatment. [Extracted from the article]

Summary: Lymphoma‐associated haemophagocytic syndrome (LAHS) accounts for most cases of secondary haemophagocytic syndrome (HS) and has been extensively described in Asian populations. However, little is known about the epidemiology of LAHS in Western countries. We herein report a case series of 71 LAHS patients in which the lymphomas were mainly of the aggressive type. Diagnoses included non‐Hodgkin B cell lymphoma (46·5%) including human herpes virus 8‐associated non‐Hodgkin lymphoma (12·7%), T cell lymphoma (28·2%) and Hodgkin lymphoma (23·9%). An underlying immunodeficiency was described in 30 patients (42·3%). Early mortality within the 30 days following HS diagnosis was observed in 26·8% of cases. The overall survival was estimated at 45·7% [95% confidence interval, CI (35·4–59·0)] at 6 months, and 34·3% [95% CI (24·8–47·4)] at 2 years. Concurrent infection, age over 50 years, ethnicity and etoposide treatment were independently associated with mortality. While it appears that certain types of lymphomas were more prone to trigger HS, LAHS were not restricted to a few types of lymphoma. The overall prognosis was poor, with a particularly high rate of early mortality, highlighting the importance of both early recognition and choice of initial therapeutic management. [ABSTRACT FROM AUTHOR]

Abstract: Heavy‐chain deposition disease (HCDD) is characterized by tissue deposits of a truncated monoclonal immunoglobulin heavy‐chain (HC) on basement membranes. Diagnosis is usually made on kidney biopsy, showing nodular glomerulosclerosis with HC deposits which can be missed, resulting in delay in diagnosis. We report four γ1‐HCDD patients presenting with cutis laxa, hypocomplementemia and hypoalbuminemia. In two patients, unsuspected HCDD was revealed by cutis laxa and diagnosis was made on skin biopsy. In all patients, serum albumin and complement represented surrogate markers for disease monitoring. In γ‐HCDD, extrarenal manifestations such as cutis laxa may precede renal injury and are precious tools for an early diagnosis, which is crucial to avoid progression of irreversible renal and elastic tissue damage. [ABSTRACT FROM AUTHOR]

Nonadherence to treatment is a major cause of lupus flares. Hydroxychloroquine (HCQ), a major medication in systemic lupus erythematosus, has a long half‐life and can be quantified by high‐performance liquid chromatography. This international study evaluated nonadherence in 305 lupus patients with flares using drug levels (HCQ <200 ng/ml or undetectable desethylchloroquine), and self‐administered questionnaires (MASRI <80% or MMAS‐8 <6). Drug levels defined 18.4% of the patients as severely nonadherent. In multivariate analyses, younger age, nonuse of steroids, higher body mass index, and unemployment were associated with nonadherence by drug level. Questionnaires classified 39.9% of patients as nonadherent. Correlations between adherence measured by questionnaires, drug level, and physician assessment were moderate. Both methods probably measured two different patterns of nonadherence: self‐administered questionnaires mostly captured relatively infrequently missed tablets, while drug levels identified severe nonadherence (i.e., interruption or erratic tablet intake). The frequency with which physicians miss nonadherence, together with underreporting by patients, suggests that therapeutic drug monitoring is useful in this setting. (Trial registration: ClinicalTrials.gov: NCT01509989.) [ABSTRACT FROM AUTHOR]

Summary: The spectrum of Castleman disease (CD) has considerably extended since its first description in 1956. Recently, an international collaborative working group has reached consensus on the diagnostic criteria and classification of CD. We herein report 273 patients with lymph node histopathology consistent with CD and investigate the newly established diagnostic criteria. Twenty of these patients with Castleman‐like histopathology were removed from analyses, because they were diagnosed with an exclusionary disorder (18 with haematological malignancy). Among the 253 remaining patients, 57 were considered unicentric CD (UCD), 169 were multicentric CD associated with Human Herpesvirus 8 (HHV‐8+MCD), including 140 patients with human immunodeficiency virus (HIV) infection and 29 patients without HIV infection, and 27 were HHV‐8 negative/idiopathic multicentric CD (iMCD). 2‐(18F)fluoro‐2‐deoxy‐D‐glucose positron emission tomography/computed tomography was useful in 62 patients for staging/classification of the disease and for excluding associated lymphoma. UCD was mainly associated with hyaline‐vascular histopathological features, and most patients were asymptomatic. Of the 27 patients that we had originally diagnosed with iMCD, 26 met the newly established diagnostic criteria. Patients with iMCD and HHV‐8+ MCD demonstrated similar characteristics, including fever, splenomegaly, cytopenia and inflammatory symptoms. However, the disease was more aggressive in HHV‐8+ MCD, particularly in HIV‐infected patients. [ABSTRACT FROM AUTHOR]

Background Data on plasma exchange therapy in the intensive care unit (ICU) setting are scarce. We aimed to describe the technical aspects and the adverse events associated with the procedure in critically ill patients. Methods All adult patients treated by plasma exchange in the medical ICU of the Saint-Louis university hospital between January 1, 2013 and March 31, 2015 were prospectively included. Results We report on 260 plasma exchange procedures performed in 50 patients. The centrifugation technique was used for 159 (61%) procedures and the filtration technique for the other 101 (39%) procedures. Both techniques had similar efficacy to treat hyperviscosity syndrome ( n = 18). Seventy (26.9%) of the 260 plasma exchange procedures were reported with at least one adverse reaction. Centrifugation and filtration techniques had similar rates of adverse reactions (23.9 vs. 31.7%, P = .19). Hypotension was the most reported ( n = 21, 8%) and correlates with a low hematocrit before therapy. Most complications were related to allergic reactions to the replacement fluids. Coagulation disorders depended on the type of replacement fluid. The post-exchange fibrinogen level was decreased by 54% [48;66] with albumin 5%, and 4% [−5;17] with plasma frozen within 24 h. Twenty-three (22.8%) of the 101 filtration procedures experienced filter clotting. Filter clotting was associated with a higher volume exchange prescribed when compared to procedures without filter clotting (4600 [4000;5000] ml vs. 3900 [3600;4800] ml, P < .01). Conclusion Plasma exchange is a relatively safe and generally well-tolerated procedure in the ICU setting. Most adverse events are unpredictable and related to minor allergic reactions. [ABSTRACT FROM AUTHOR]

Central nervous system ( CNS) involvement is reportedly more common in acquired immunodeficiency syndrome ( AIDS)-related lymphomas ( ARL). We describe factors and outcomes associated with CNS involvement at baseline ( CNSB) and relapse ( CNSR) in 886 patients with newly diagnosed ARL. Of 886 patients, 800 received either intrathecal ( IT) therapy for CNSB or IT prophylaxis. CNSB was found in 13%. CNSB was not associated with reduced overall survival ( OS). There was no difference in the prevalence of CNSB between the pre-combination antiretroviral therapy ( cART) and cART eras. 5·3% of patients experienced CNSR at a median of 4·2 months after diagnosis (12% if CNSB; 4% if not). Median OS after CNSR was 1·6 months. On multivariate analysis, only CNSB [hazard ratio ( HR) 3·68, P = 0·005] and complete response to initial therapy ( HR 0·14, P < 0·0001) were significantly associated with CNSR. When restricted to patients without CNSB, IT CNS prophylaxis with 3 vs. 1 agent did not significantly impact the risk of CNSR. Despite IT CNS prophylaxis, 5% of patients experienced CNSR. Our data confirms that CNSR in ARL occurs early and has a poor outcome. Complete response to initial therapy was associated with a reduced frequency of CNSR. Although CNSB conferred an increased risk for CNSR, it did not impact OS. [ABSTRACT FROM AUTHOR]

This retrospective analysis was conducted in 64 patients diagnosed with type I cryoglobulinaemia ( CG) followed at two French centres. Median follow-up was 6·75 years. CG was IgG in 60% and IgM in 40% of all cases and was asymptomatic in 16 patients (25%). Cold-triggered ischaemic skin manifestations were observed in 33 patients (51%). Neurological manifestations were observed in 15 patients and renal manifestations in 13. Most of the patients with necrotic purpura (14/16, P = 0·009) and renal manifestations (11/13, P = 0·057) had IgG CG. IgG CG was associated with monoclonal gammopathy of undetermined significance ( MGUS), myeloma, chronic lymphocytic leukaemia and lymphoplasmocytic lymphoma in 18, 13, 5 and 2 patients, respectively. IgM CG was associated with MGUS and Waldenström macroglobulinaemia in 8 and 18 cases, respectively. One third of patients did not receive any specific treatment. Various treatments, including rituximab, were administered to 25/31 patients with IgG CG and 6/25 patients with IgM CG due to CG-related symptoms. Rituximab was ineffective in all cases associated with a predominantly plasmacytic proliferation. To conclude, type I CG has specific clinico-biological characteristics compared to type II CG. Furthermore, there are differences in terms of related manifestations between type I IgG and type I IgM CG. [ABSTRACT FROM AUTHOR]

Reactive haemophagocytic syndrome is a life-threatening disease for which factors influencing the outcome remain unclear. We sought to identify determinants of early mortality in patients with reactive haemophagocytic syndrome by conducting a non-interventional retrospective multicentre study in three tertiary care teaching hospitals over a 6-year period. The medical files of 162 patients fulfilling our diagnostic criteria of haemophagocytic syndrome were reviewed. Patients were classified according to 30-d outcome following diagnosis. Thirty-three patients (20·4%) died within 30 d. Clinical features at diagnosis associated with 30-d death in univariate analysis were older age ( P = 0·004), underlying lymphoma ( P = 0·04), lower platelet count ( P = 0·001) and elevated aspartate aminotransferase and lactate dehydrogenase ( P = 0·04 both). The use of etoposide as a first-line treatment tended to be associated with a better outcome ( P = 0·079). In multivariate analyses, increasing age, decreasing platelet count, underlying lymphoma and no etoposide in the management were associated with a poorer prognosis ( P = 0·03, 0·01, 0·003 and 0·04, respectively). These prognostic factors could help to identify those patients more severely affected by reactive haemophagocytic syndrome, who should benefit from aggressive supportive care, combined with specific treatment of the precipitating factor. [ABSTRACT FROM AUTHOR]

The article discusses the cases of patients with autoimmune thrombotic thrombocytopenic purpura (TTP) concomitant with human herpes virus 8 (HHV8)-related multicentric Castleman disease (MCD). Topics discussed include the symptoms of TTP which is a thrombotic microangiopathy (TMA), HIV infection in TMA/MCD patients, and the management of the patient through therapeutic plasma exchange (TPE) in combination with steroids.

Objective Because it has no unique clinical, biologic, or histologic features, reactive hemophagocytic syndrome may be difficult to distinguish from other diseases such as severe sepsis or hematologic malignancies. This study was undertaken to develop and validate a diagnostic score for reactive hemophagocytic syndrome. Methods A multicenter retrospective cohort of 312 patients who were judged by experts to have reactive hemophagocytic syndrome (n = 162), were judged by experts to not have reactive hemophagocytic syndrome (n = 104), or in whom the diagnosis of reactive hemophagocytic syndrome was undetermined (n = 46) was used to construct and validate the reactive hemophagocytic syndrome diagnostic score, called the HScore. Ten explanatory variables were evaluated for their association with the diagnosis of hemophagocytic syndrome, and logistic regression was used to calculate the weight of each criterion included in the score. Performance of the score was assessed using developmental and validation data sets. Results Nine variables (3 clinical [i.e., known underlying immunosuppression, high temperature, organomegaly], 5 biologic [i.e., triglyceride, ferritin, serum glutamic oxaloacetic transaminase, and fibrinogen levels, cytopenia], and 1 cytologic [i.e., hemophagocytosis features on bone marrow aspirate]) were retained in the HScore. The possible number of points assigned to each variable ranged from 0-18 for known underlying immunosuppression to 0-64 for triglyceride level. The median HScore was 230 (interquartile range [IQR] 203-257) for patients with a positive diagnosis of reactive hemophagocytic syndrome and 125 (IQR 91-150) for patients with a negative diagnosis. The probability of having hemophagocytic syndrome ranged from <1% with an HScore of ≤90 to >99% with an HScore of ≥250. Conclusion The HScore can be used to estimate an individual's risk of having reactive hemophagocytic syndrome. This scoring system is freely available online (). [ABSTRACT FROM AUTHOR]

Purpose Multicentric Castleman disease ( MCD) is a distinct lymphoproliferative disorder characterized by inflammatory symptoms, lymphadenopathy, splenomegaly, and cytopenia. Kaposi's sarcoma-associated herpesvirus ( KSHV), also called human herpesvirus-8 ( HHV-8), is the cause of virtually all cases of MCD occurring in patients with HIV infection. MCD lesions characteristically contain HHV-8-infected polyclonal IgMλ plasmablasts. A high frequency of HHV-8-related non-Hodgkin lymphoma has been reported in these patients. Patients and methods We now report on three patients who presented with severe symptoms of MCD, extreme splenomegaly, and rapid expansion of B-cell lymphocytosis (44-81%) attributable to circulating HHV-8 positive plasmablasts. Results The circulating plasmablastic cells shared the phenotype (IgMλ, CD19+, CD20− CD138−) of HHV-8-infected cells from MCD lesions, mimicking the leukemic phase of large B-cell lymphoma occurring in HHV-8-related MCD. These patients displayed a very high HHV-8 viral load in blood (>7 logs HHV-8 DNA copies/ml) and high levels of serum vIL-6, the viral homolog of human interleukin 6. Serum IL-6 and IL-10 were also abnormally elevated. HHV-8-infected cells were demonstrated by immunoglobulin gene rearrangement analysis, to be polyclonal and likely represent an expansion of HHV-8-infected cells similar to those found in MCD lesions. Conclusion Thus, the spectrum of HHV-8-related plasmablastic lymphoproliferative disorders in patients with HIV infection is expanded to include HHV-8+ polyclonal IgMλ B-cell lymphocytosis. At onset, this lymphoproliferative disorder may mimic plasmablastic leukemia/lymphoma. Recognizing this unusual complication may have important implications in treatment decision avoiding unnecessary toxicity to the patients. [ABSTRACT FROM AUTHOR]

In tumour lysis syndrome ( TLS), metabolic alterations caused by the destruction of malignant cells manifest as laboratory abnormalities with (clinical TLS) or without (laboratory TLS) organ dysfunction. This prospective multicentre cohort study included 153 consecutive patients with malignancies at high risk for TLS (median age 54 years (interquartile range, 38-66). Underlying malignancies were acute leukaemia (58%), aggressive non-Hodgkin lymphoma (29.5%), and Burkitt leukaemia/lymphoma (12.5%). Laboratory TLS developed in 17 (11.1%) patients and clinical TLS with acute kidney injury ( AKI) in 30 (19.6%) patients. After adjustment for confounders, admission phosphates level (odds ratio [ OR] per mmol/l, 5.3; 95% confidence interval [95% CI], 1.5-18.3), lactic dehydrogenase ( OR per x normal, 1.1; 95% CI, 1.005-1.25), and disseminated intravascular coagulation ( OR, 4.1; 95% CI, 1.4-12.3) were associated with clinical TLS; and TLS was associated with day-90 mortality ( OR, 2.45; 95% CI, 1.09-5.50; P = 0.03). In this study, TLS occurred in 30.7% of high-risk patients. One third of all patients experienced AKI, for which TLS was an independent risk factor. TLS was associated with increased mortality, indicating a need for interventional studies aimed at decreasing early TLS-related deaths in this setting. [ABSTRACT FROM AUTHOR]

Most cases of human immunodeficiency virus ( HIV)-associated non- Hodgkin Lymphoma ( NHL) are of B-cell origin; T-cell NHLs are rarely reported. Within a single centre prospective cohort of 370 HIV- NHL, 17 (5%) were of T-cell origin (82% male; median age, 39 years). Median CD4+ cell count was 0·194 × 109/l and 41% had undetectable plasma HIV- RNA at lymphoma diagnosis. All patients received combination antiretroviral therapy during chemotherapy. All histological samples were centrally reviewed. The distribution of the histological subtypes differed from the general population with absence of angioimmunoblastic subtype. Lymphoma was disseminated in 14 patients, and seven patients had performance status >2. All patients received full-dose chemotherapy: eight standard and nine intensive regimens. Two patients who received intensive chemotherapy died during therapy. The complete remission rate was 53%; 62·5% with standard therapy and 44% with intensive therapy. After a median follow-up of 7·2 years, the median overall survival was 9·4 months. Most deaths (85%) occurred within the first year following diagnosis, as a consequence of lymphoma progression in 10/13 cases. In this rare but severe complication of HIV infection the use of intensive chemotherapy does not appear to be beneficial for response, with increased toxicity. [ABSTRACT FROM AUTHOR]

BACKGROUND: The objective was to assess the efficacy and safety of splenectomy and cyclophosphamide as salvage therapies in severe thrombotic thrombocytopenic purpura (TTP). STUDY DESIGN AND METHODS: During a 10-year period, patients who did not improve with plasma exchanges, steroids, vincristine, and/or rituximab were considered for splenectomy or cyclophosphamide. Patients with a documented severe (<10% of normal value) acquired ADAMTS13 deficiency are reported here. RESULTS: Eighteen patients with a severe acquired ADAMTS13 deficiency required a salvage therapy. Thirteen patients had a splenectomy 19 (interquartile range [IQR], 10-51) days after TTP diagnosis. One patient died the day after splenectomy. The remaining patients improved platelets (PLTs) until Day 6, along with a rapid and major lactate dehydrogenase improvement. Six patients, however, subsequently experienced a transient worsening. Durable PLT count recovery in survivors was observed within 13 (IQR, 11.5-25.5) days. Postoperative complications included thromboembolic events (two cases) and infections (five cases). Five patients received pulses of cyclophosphamide 12 (IQR, 12-15) days after TTP diagnosis. All patients recovered PLTs 10 (IQR, 9-24) days after the first pulse and two experienced a transient worsening. Three patients experienced infections. Three relapses occurred 5 months, 2.5 years, and 4.5 years after splenectomy and one relapse occurred 3.5 years after cyclophosphamide. After a 2.5 (IQR, 0.75-6.2)-year follow-up, the overall survival was 94%. CONCLUSION: Cyclophosphamide and splenectomy provide comparable high remission rates in severe TTP with acceptable side effects and should be considered in the more severe patients who do not improve with other therapies. [ABSTRACT FROM AUTHOR]

The risk of developing Hodgkin lymphoma ( HL) is increased in immunodeficiencies or during the treatment of some autoimmune diseases. The development of new therapeutic agents has highlighted the risk of unusual lymphoid proliferations, particularly classical HL (c HL). We report the clinicopathological findings of 13 c HL arising in patients treated for a primary haematological malignancy. Eight patients had received an immunomodulator, protein tyrosine-kinase inhibitor or monoclonal antibody, which may have contributed to the c HL development. Most patients had disseminated disease with poor prognostic factors at cHL diagnosis. Despite the initial presentation, good outcomes were achieved with standard c HL chemotherapy. [ABSTRACT FROM AUTHOR]

Summary Patients with common variable immunodeficiency (CVID) are at high risk of developing immune thrombocytopenia (ITP) and/or autoimmune haemolytic anaemia (AHA). Given their underlying immunodeficiency, immunosuppressive treatment of these manifestations may increase the risk of infection. To assess efficacy and safety of rituximab in patients with CVID-associated ITP/AHA, a multicentre retrospective study was performed. Thirty-three patients, 29 adults and four children, were included. Patients received an average of 2·6 treatments prior to rituximab including steroids, intravenous immunoglobulin and splenectomy (21%). The median ITP/AHA duration at time of first rituximab administration was 12 months [range 1-324] and the indication for using rituximab was ITP (22 cases), AHA ( n = 5) or both ( n = 7); 1 patient was treated sequentially for ITP and then AHA. The overall initial response rate to rituximab was 85% including 74% complete responses. After a mean follow-up of 39 ± 30 months after rituximab first administration, 10 of the initial responders relapsed and re-treatment with rituximab was successful in 7/9. Severe infections occurred after rituximab in eight adults (24%), four of whom were not on immunoglobulin replacement therapy. In conclusion, rituximab appears to be highly effective and relatively safe for the management of CVID-associated severe immune cytopenias. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cold autoagglutinins (CAs) are almost always of immunoglobulin (Ig)M class and specific for carbohydrate antigens. We report a case of hemolytic anemia caused by a mixture of IgM and IgG cold agglutinins. Both agglutinins were specific for the third extracellular loop of band 3. CASE REPORT: The patient, a 46-year-old man with no medical history, was admitted for an acute, life-threatening hemolytic anemia caused by a cold agglutinin. Improvement was obtained after plasmapheresis, red blood cell (RBC) transfusions, and steroid therapy. Recovery was complete and no etiology was found. STUDY DESIGN AND METHODS: Conventional serologic procedures and immunochemical methods were used. RESULTS: The patient's autoantibody was directed to an antigen equally expressed by adult and cord RBCs, resistant to papain, neuraminidase, and endo-β-galactosidase treatments. This pattern of reactivity excluded all known specificities of cold agglutinins. The antibody failed to react with RBCs treated by α-chymotrypsin or pronase, suggesting that it may be directed to the third extracellular loop of band 3. Serum fractionation showed that the cold agglutinin was composed of IgM and IgG class antibodies. Antibody specificity was confirmed by blocking tests using murine monoclonal antibodies against band 3 and by immunoprecipitation. CONCLUSION: This is to our knowledge the first observation of a CA specific for band 3. The coexistence of IgM and IgG molecules, a very unusual feature for a CA, may be related to the peptidic nature of the target antigen. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Development and validation of the HScore, a score for the diagnosis of reactive hemophagocytic syndrome" in the September 2014 issue is presented.