Clinical Characteristics And Prognostic Analysis Of Adult Lymphoma-associated Hemophagocytic Syndrome

BackgroundHemophagocytic syndrome(HPS),also known as hemophagocytic lymphohistiocytosis(HLH),is an abnormally high-inflammatory,high-ferritin immune response syndrome,driven by T cells and accompanied by potential The deadly cytokine storm eventually caused multiple organ failure and even death.According to the pathogenesis,it is divided into primary(hereditary)HLH and secondary(acquired)HLH.Hereditary or primary HLH is composed of several genetic heterogeneous diseases,including familial HLH 2-5,Griscelli synthesis Sign II and X-linked lymphoproliferative syndrome.Primary HLH occurs mainly in childhood and may be induced by infection.As with primary HLH,acquired or secondary HLH is not a separate disease entity.In contrast,secondary HLH represents a group of diseases that can occur in multiple situations and is more common in adults.The most common cause of infection is infection,especially when infected with infections such as Epstein-Barr virus(EBV)and cytomegalovirus(CMV).However,the disease can also be induced by certain malignancies,autoimmune or autoinflammatory diseases.Because of their rarity,and the heterogeneity of incentives and clinical outcomes,the diagnosis and treatment of secondary forms of HLH remains challenging.The substantial overlap between the characteristics of HLH and the characteristics of tumors makes the identification of HLH occurring in malignant situations very difficult.Malignancy-associated hemophagocytic syndrome(M-HLH),especially Lymphoma-associated haemophagocytic syndrome(LAHS),is a secondary hemophagocytic syndrome(sHPS).One of the important causes is that the incidence rate increases with age,the disease progresses quickly,early clinical diagnosis is difficult,and the mortality rate is high.Therefore,early diagnosis and initial treatment are important to improve lymphoma-related HLH.The purpose of this study is to retrospectively analyze the clinical characteristics,treatment and prognostic factors of patients with lymphoma-associated HLH in order to improve the understanding of this disease and achieve early diagnosis and early treatment.MethodsRetrospective analysis of clinical data of patients diagnosed with LAHS at the First Affiliated Hospital of Zhengzhou University from December 2012 to December 2018ResultsA total of 43 patients were diagnosed with LAHS,including 25 males and 18 females.The median age was 37 years and the age was 18-78 years.Twenty-seven patients were diagnosed with NK/T-cell lymphoma,accounting for 62.8%of all patients with LAHS.The most common type of histopathology is extranodal natural killer/T-cell lymphoma,with nasal type(ENKL)accounting for 21(48.8%).B-cell lymphomas were diffuse large B-cell lymphomas in 14 cases(32.6%),the rest were angioimmunoblastic T-cell lymphomas in 2 cases(4.6%),and subcutaneous panniculitis-like T-cell lymphomas in 2 cases.(4.6%),2 cases of Hodgkin’s lymphoma(4.6%),1 case of anaplastic large cell lymphoma(2.3%),and 1 case of peripheral T-cell lymphoma(2.3%).Lymphoma-induced HLH,or HLH,occurred in 37 cases(86%)at the time of initial diagnosis or recurrence of lymphoma,while chemotherapy-related HLH occurred in 6 cases(14%)of HLH during chemotherapy or maintenance therapy,of which HLH The time from onset of lymphoma diagnosis ranges from 0 to 32 months,with a median time of 6 months.The most common clinical signs and symptoms are fever(100%),followed by splenomegaly(86%),hepatomegaly(39.6%),edema(25.6%),bleeding from the skin and mucous membranes(25.6%),and polyserosal fluid(25.6%)and jaundice(23.3%).Regarding laboratory test results,the most common are hyperferritinemia(100%),hyperlactate dehydrogenase(76.7%),hypofibrinogenemia(65.1%),and grade Ⅲ/Ⅳthrombocytopenia(62.8%),hypertriglyceridemia(62.8%),gradeⅢ/Ⅳ neutropenia(48.8%),and severe anemia(16.3%).Seventeen patients(39.6%)were positive for peripheral blood EBV virus(5 of them had no EBV test results).Of the 43 patients,32 had phagocytosis(74.4%).Kaplan-Meier analysis found that the OS of NK/T-cell LAHS patients was worse than that of B-cell LAHS patients.High LDH and low fibrinogenemia were significantly associated with decreased survival(P=0.001,0.001).Patients with etoposide and hematopoietic stem cell transplantation have a relatively good prognosis.In addition,multivariate analysis showed that age,splenomegaly,low absolute neutrophil counts,low platelets,high lactate dehydrogenase,and high triglyceride concentrations were independent prognostic factors for all patients with LAHS.Conclusions1.The early clinical manifestations of lymphoma-associated HLH in adults are often atypical,and patients with lymphoma associated with high fever,cytopenia,abnormal coagulation function,and/or hyperferritinemia should be highly suspected of lymphoma-associated HLH.2.NK/T-cell lymphoma is the most common lymphoma-related HLH in adults,and the incidence of ENKL is the highest.3.Adult patients with lymphoma-associated hemophagocytic syndrome progress rapidly and have a high case fatality rate.Early diagnosis and appropriate immunochemotherapy plus HSCT are essential to improve outcomes.4.HSCT is an effective way to prolong the survival of patients with lymphoma-related HLH.5.The overall prognosis of lymphoma-associated HLH is poor.Patients with NK/T cell LAHS have a worse prognosis.Patients with high LDH and low fibrinogen have a worse prognosis.Old age,splenomegaly,low absolute neutrophil counts,low platelets,high lactate dehydrogenase,and high triglyceride concentrations are independent prognostic factors for all patients with LAHS.