Central nervous system involvement in adult-onset hemophagocytic lymphohistiocytosis secondary to lymphoma: a case presentation and literature analysis
Ontology highlight
ABSTRACT:
SUBMITTER: He T
PROVIDER: S-EPMC10239994 | biostudies-literature | 2023 Apr
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Opinion statementCentral nervous system (CNS)-hemophagocytic lymphohistiocytosis (HLH) is not a disease in itself, but it is part of a systemic immune response. The vast majority of patients with CNS-HLH also have systemic HLH and a large number of patients with primary and secondary HLH have CNS involvement. Reactivations within the CNS are frequent during the course of HLH treatment and may occur concomitant with or independent of systemic relapses. It is also important to consider primary HLH as an underlying cause of "unknown CNS inflammation" as these patients may present with only CNS disease. To initiate proper treatment, a correct diagnosis must be made. A careful review of the patient's history and a thorough neurological examination are essential. In addition to the blood tests required to make a diagnosis of HLH, a lumbar puncture with cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI) should always be done in all cases regardless of the presence or absence of neurological signs or symptom. Treatment options for CNS-HLH include, but are not limited to, those commonly used in systemic HLH, including corticosteroids, etoposide, cyclosporine A, alemtuzumab, and ATG. In addition, intrathecal treatment with methotrexate and corticosteroids has become a standard care and is likely to be beneficial. Therapy must be initiated without inappropriate delay to prevent late effects in HLH. An interesting novel approach is an anti-IFN-gamma antibody (NI-0501), which is currently being tested. Hematopoietic stem cell transplantation (HSCT) also represents an important CNS-HLH treatment; patients with primary HLH may benefit from immediate HSCT even if there is active disease at time of transplantation, though care should be taken to monitor CNS inflammation through HSCT and treat if needed. Since CNS-HLH is a condition leading to the most severe late effects of HLH, early expert consultation is recommended.
| S-EPMC5290057 | biostudies-literature
Project description:The diagnosis of hemophagocytic lymphohistiocytosis (HLH) with cerebral involvement is challenging given the rarity of HLH and its resemblance to the much more common severe sepsis. Timely diagnosis and treatment may be lifesaving. We report two cases demonstrating different and rare forms of severe brain involvement in adult patients with HLH: acute necrotizing encephalopathy, and diffuse hemorrhagic disease due to disseminated intravascular coagulation. Severe HLH with brain involvement in adults is rare. HLH with cerebral involvement should be considered in patients presenting with severe systemic inflammatory response syndrome (SIRS) but negative cultures and unusual or unexpectedly severe clinical and/or radiologic signs of cerebral dysfunction. Similar brain injury may occur in patients with cytokine storm syndrome due to COVID-19. BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) presents with fevers, rash, organomegaly, cytopenia, and increased triglycerides and ferritin (Ramos-Casals et al., 2014) [1]. Neurologic abnormalities are reported in about one-third of patients (Cai et al., 2017), including a few cases of acute necrotizing encephalopathy (ANE) (Xiujuan et al., 2015). Coagulation abnormalities are frequent in HLH patients (Valade et al., 2015). OBJECTIVE: To raise awareness about the importance of early diagnosis and treatment of HLH with neurological involvement to prevent serious complications and demise.
| S-EPMC7162634 | biostudies-literature
Project description:IntroductionHemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening condition. This study aimed to evaluate treatment outcomes and identify prognostic-related factors in Thai children with HLH.Materials and methodsWe retrospectively reviewed the medical records of 76 pediatric patients with HLH who were treated at Ramathibodi Hospital between January 2004 and December 2019. Treatment outcomes were defined as early mortality (death within 30 days after diagnosis) and early treatment response (resolution of all clinical features and normalization of at least one HLH-related laboratory parameter within 4 weeks).ResultsThe overall mortality rate was 38% (29/76), with an early mortality rate of 45% (13/29). Malignancy-associated HLH had the highest mortality rate (88%), followed by primary HLH (56%). The predictors of early mortality were central nervous system (CNS) involvement [OR 13 (95%CI 2-83), p = 0.007] and platelet counts <44 × 106/mm3 [OR 8 (95%CI 1.3-49), p = 0.024]. The predictors of early treatment response were no CNS involvement [OR 6.6 (95%CI 1.5-28.8), p = 0.011], platelet counts more than 44 × 106/mm3 [OR 8 (95%CI 2.1-30.9), p = 0.003], and total bilirubin levels <1.8 mg/dL [OR 4 (95%CI 1.1-14.8), p = 0.036]. In the mixed-model analysis, platelet counts in non-survivors increased significantly less than those in survivors, with a mean difference in platelet changes between the two groups of 94.6 × 106/mm3 (p = 0.003).ConclusionThe independent predictors of early mortality in children with HLH were CNS involvement and low baseline platelet counts. A slow rate of platelet increases during the first week after diagnosis was also associated with mortality.
| S-EPMC9485874 | biostudies-literature
Project description: Not available
| S-EPMC6391665 | biostudies-literature
Project description:Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by hyperinflammation in an uncontrolled and ineffective immune response. Despite great improvement in diagnosis and treatment, it still represents a challenge in clinical management, with poor prognosis in the absence of an aggressive therapeutic approach. The present literature review focuses on secondary HLH at pediatric age, which represents a heterogeneous group in terms of etiology and therapeutic approach. It summarizes the most recent evidence on epidemiology, pathophysiology, diagnosis, treatment and prognosis, and provides a detailed description and comparison of the major subtypes of secondary HLH. Finally, it addresses the open questions with a focus on diagnosis and new treatment insights.
| S-EPMC10433411 | biostudies-literature
Project description: Not available
| S-EPMC7938066 | biostudies-literature
Project description:Secondary central nervous system large B-cell lymphoma (SCNSL) is rare, with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression-free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal lactate dehydrogenase, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (hazard ratio [HR], 0.278; 95% CI, 0.153-0.506; P ≤ .0001) and ≤2 prior lines of therapy (HR, 0.485; 95% CI, 0.274-0.859; P = .0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR, 0.352; 95% CI, 0.186-0.663; P = .0013) and ≤2 prior lines of therapy (HR, 0.476; 95% CI, 0.257-0.882; P = .0183) were associated with improved survival. In the largest single-center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those who received ≤2 lines of therapy have particularly excellent outcomes.
| S-EPMC9006305 | biostudies-literature
Project description: Not available
| S-EPMC8968463 | biostudies-literature
Project description:BackgroundFive fulfilled hemophagocytic lymphohistiocytosis (HLH)-2004 criteria, and the HScore are widely used and recommended by international expert consensus to diagnose secondary HLH. Both diagnostic scores have never been validated in heterogeneous patient cohorts of secondary HLH patients. We aimed to systematically optimize and validate diagnostic criteria of secondary HLH using a multicenter approach.MethodsWe developed optimized criteria in our cohort of critically ill patients as a first step. We next validated these new criteria together with the original and modified HLH-2004 criteria as well as the HScore using original data of 13 published cohorts, which were identified by a systematic literature search.ResultsThe best performing HLH diagnostic criteria sets over all 13 validation cohorts were the original HLH-2004 criteria with a decreased cut-off (cut-off 4, mean sensitivity 86.5%, mean specificity 86.1%), followed by the revised HLH-2004 criteria (natural killer cell activity removed; cut-off 4, mean sensitivity 83.8%, mean specificity 87.8%) and the HScore (cut-off 169, mean sensitivity 82.4%, mean specificity 87.6%). Our newly developed HLH diagnostic criteria showed inferior performance. Ferritin ≥500 µg/L had 94.0% mean sensitivity over all cohorts.ConclusionsIn this first multicenter validation study, four fulfilled HLH-2004 criteria and an HScore of 169 were suitable to diagnose secondary HLH, which will lead to rapid diagnosis and improved patient outcomes. Ferritin proved as a reliable HLH screening marker. Our results should be taken into account in clinical recommendations and in designing new studies.
| S-EPMC11846073 | biostudies-literature
Project description:Hemophagocytic lymphohistiocytosis (HLH) is a fatal systemic inflammatory syndrome. HLH has been reported as a rare immune-related adverse event (irAE) in patients receiving immunotherapy with nivolumab, ipilimumab, and/or pembrolizumab. The data are limited to case reports and case series. The objective of this research is to compile data on this rare but potentially life-threatening adverse event of immune checkpoint inhibitors (ICIs) and identify the common agents that cause this irAE, clinical spectrum, and successful management strategies to assist the treating oncologists. A review was done using PubMed database. Eligible articles included case reports and case series published from January 1, 2015, through February 1, 2021. Reports published in languages other than English were excluded. Data were compiled into a detailed supplementary table and simple descriptive analysis was used to interpret data. A total of 22 cases were included, which constituted 14 individual case reports and two case series. The immunotherapy prescribed consisted of antibodies against and programmed cell death 1 (PD-1) or its ligand, programmed cell death ligand 1 (PD-L1) in all 22 patients. Out of them, immunotherapy consisting of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) antibodies was prescribed in nine patients. Fever was the most common symptom at the presentation (90.9%). The most common laboratory findings were anemia (90.9%), thrombocytopenia (90.9%), and elevated ferritin (90.9%). All the patients received steroids (100%). HLH responded to treatment in 19 patients. Three patients died. Three patients were rechallenged with immunotherapy, with no recurrence of HLH. HLH in the setting of ICI therapy is life-threatening, but potentially treatable with early detection. However, diagnosis is often delayed due to difficulty in differentiating the presenting symptoms and laboratory findings from complications of cancer and other therapies. Majority have shown an adequate response to standard HLH treatment; however, some required a longer course of corticosteroids. HLH is not always associated with other irAE. Rechallenging with immunotherapy was successful in some patients after completing treatment for HLH.
| S-EPMC9076146 | biostudies-literature