Successful treatment of severe splenic lymphoma­associated hemophagocytic syndrome by splenectomy and subsequent chemotherapy: A case report.

Hemophagocytic lymphohistiocytosis (HLH) represents a fatal immunopathology derived from excessive inflammatory reactions. In particular, lymphoma-associated hemophagocytic syndrome (LAHS) is associated with a dismal prognosis. The current study presented a challenging case of splenic LAHS. A 71-year-old man presented with fatigue and anorexia. Laboratory test results revealed anemia, thrombocytopenia, lactate dehydrogenase elevation and markedly elevated levels of ferritin (6,210 ng/ml) and soluble interleukin 2 receptor (sIL-2R; 11,328 U/ml). Abdominal computed tomography revealed marked splenomegaly, while fluorodeoxyglucose positron emission tomography revealed increased tracer uptake in the spleen. An elective splenectomy was performed, which led to the diagnosis of B-cell splenic lymphoma with transformation from indolent to aggressive lymphoma. Prior to the splenectomy, thrombocytopenia and hepatic dysfunction with rapidly progressing jaundice appeared, accompanying further elevation of ferritin (25,197 ng/ml) and sIL-2R levels (30,420 U/ml). On postoperative day 5, the patient was transferred to a tertiary care institution and corticosteroid pulse therapy was immediately initiated after establishing the diagnosis of LAHS. Liver dysfunction gradually recovered and subsequent chemotherapy resulted in complete remission with improved performance status. At eight months after the onset, the patient remains alive without any signs of residual lymphoma. Although splenic lymphoma typically manifests with low-grade lymphoma, it can transform into high-grade lymphoma associated with severe complications, such as HLH and multiple organ failure. In this case, splenectomy assisted in not only establishing the diagnosis but also in tumor cytoreduction before commencing chemotherapy. Through interdisciplinary collaboration, the patient was successfully treated by performing a timely splenectomy, followed by steroid pulse therapy and chemotherapy.

[Gene Polymorphisms of Patients with Lymphoma-Associated Hemophagocytic Syndrome in Longyan area, Fujian Province].

OBJECTIVE: To analyze the gene polymorphisms of patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. METHODS: A total of 125 patients with lymphoma-associated hemophagocytic syndrome in Longyan, Fujian province, admitted to Longyan First Hospital from May 2017 to November 2020 were selected. Peripheral venous blood was collected from all the patients, and the genotypes of perforin 1 (PRF1) and interleukin-10 (IL-10) gene loci were detected by PCR-fluorescence probe method, and the correlation between PRF1 and IL-10 gene polymorphisms and lymphoma-associated hemophagocytic syndrome was analyzed. RESULTS: The mutation frequencies of PRF1 gene loci rs885821 (C>T), rs885822 (C>T), rs1889490 (G>A) in patients with lymphoma-associated hemophagocytic syndrome were 10.40%, 78.8% and 64.4%, respectively. The mutation frequencies of rs1800872 (A>C), rs1800871 (C>T) and rs1800896 (G>A) of IL-10 loci were 56.0%, 45.2% and 77.6%, respectively. CONCLUSION: PRF1 and IL-10 gene loci were polymorphic in patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. Alleles C and G of PRF1 and IL-10 were risk factors, and alleles T and A were protective factors.

Hemophagocytic lymphohistiocytosis secondary to diffuse large B-cell lymphoma presenting with recurrent multi-territory infarcts: A case report.

Lymphoma-associated hemophagocytic syndrome is a life-threatening disease with poor prognosis and may present as ischemic stroke. We report a case of a 56-year-old female with recurrent multi-territory infarcts caused by diffuse large B-cell lymphoma with secondary hemophagocytic lymphohistiocytosis. She had been diagnosed with ischemic stroke and hemophagocytic syndrome probably secondary to Epstein-Barr virus infection 3 months previously and treated with Dexamethasone and Aspirin. High resolution vessel wall magnetic resonance imaging showed vessel wall thickening at some intracranial vessels suggesting vasculitis. Abdominal computed tomography scan revealed splenomegaly, multiple bilateral small nodules of the lung, multiple liver lesions, multiple bilateral renal masses, gastric wall thickening and multiple nodules in the omentum. Cerebrospinal fluid cytology showed increased cerebrospinal-fluid protein level. Hemophagocytosis was showed on bone marrow aspirate cytology. Gastric tissue biopsy revealed large B cell lymphoma. Chemotherapy was not given because the patient had severe pneumonia and sepsis. The patient died 28 days after the definitive diagnosis was confirmed. Ischemic stroke in our patient with diffuse large B-cell lymphoma may be due to vasculitis or intravascular large B-cell lymphoma.

Gene Polymorphisms of Patients with Lymphoma-Associated Hemophagocytic Syndrome in Longyan area, Fujian Province / 中国实验血液学杂志

OBJECTIVE@#To analyze the gene polymorphisms of patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province.@*METHODS@#A total of 125 patients with lymphoma-associated hemophagocytic syndrome in Longyan, Fujian province, admitted to Longyan First Hospital from May 2017 to November 2020 were selected. Peripheral venous blood was collected from all the patients, and the genotypes of perforin 1 (PRF1) and interleukin-10 (IL-10) gene loci were detected by PCR-fluorescence probe method, and the correlation between PRF1 and IL-10 gene polymorphisms and lymphoma-associated hemophagocytic syndrome was analyzed.@*RESULTS@#The mutation frequencies of PRF1 gene loci rs885821 (C>T), rs885822 (C>T), rs1889490 (G>A) in patients with lymphoma-associated hemophagocytic syndrome were 10.40%, 78.8% and 64.4%, respectively. The mutation frequencies of rs1800872 (A>C), rs1800871 (C>T) and rs1800896 (G>A) of IL-10 loci were 56.0%, 45.2% and 77.6%, respectively.@*CONCLUSION@#PRF1 and IL-10 gene loci were polymorphic in patients with lymphoma-associated hemophagocytic syndrome in Longyan area, Fujian province. Alleles C and G of PRF1 and IL-10 were risk factors, and alleles T and A were protective factors.

Research progress of lymphoma-associated hemophagocytic syndrome in children / 中华实用儿科临床杂志

Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is a highly stimulated and defective inflammatory response caused by genetic inheritance or acquired immune regulation abnormalities.Lymphoma-associated hemophagocytic syndrome (LAHS) is a malignancy-associated HLH secondary to lymphoma, with a high clinical misdiagnosis rate and fatality rate and poor prognosis.In this article, the pathogenesis, diagnosis and treatment of LAHS in children were reviewed, in order to increase clinician′s understanding of the disease.

Research progress of lymphoma-associated hemophagocytic syndrome in children / 中华实用儿科临床杂志

Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is a highly stimulated and defective inflammatory response caused by genetic inheritance or acquired immune regulation abnormalities.Lymphoma-associated hemophagocytic syndrome (LAHS) is a malignancy-associated HLH secondary to lymphoma, with a high clinical misdiagnosis rate and fatality rate and poor prognosis.In this article, the pathogenesis, diagnosis and treatment of LAHS in children were reviewed, in order to increase clinician′s understanding of the disease.

Evaluation of lymphocyte function by IFN-γ secretion capability assay in the diagnosis of lymphoma-associated hemophagocytic syndrome.

Lymphoma-associated hemophagocytic syndrome (LAHS) is a highly life-threatening disease characterized by an uncontrolled immune disorder. Both under-recognition and delayed diagnosis may contribute to aggressive diseases, and a poorer prognosis. Identification of laboratory features specific for LAHS patients may allow for early detection and intervention with improved outcomes. In the present study, 120 lymphoma patients at first diagnosis were recruited and the function of lymphocytes was evaluated by IFN-γ secretion assay at first diagnosis and follow up. During the surveillance period, 20 patients who complicated with hemophagocytic lymphohistiocytosis (HLH) were classified as LAHS group, and 30 patients without infectious diseases during the course of treatment were classified as lymphoma control group. In addition, 20 non-malignant associated HLH patients recruited as HLH control group and 50 healthy control (HC) subjects were also included. The IFN-γ secretion capability of lymphocytes was compared between first diagnosis of lymphoma patients who was complicate with HLH or not in the disease progression. Our results showed that only NK cell activity was decreased in lymphoma control group, but the activities of NK, CD4+ and CD8+ T cells were all significantly decreased at the time of lymphoma diagnosis in those who would progress with HLH. During the course of treatment, lymphocyte function was relatively stable in lymphoma patients but became further decreased when suffering from complication of LAHS. The IFN-γ secretion capability of lymphocytes in LAHS and non-malignant associated HLH patients were all significantly decreased compared with HCs. So the occurrence of HLH was the key factor leading to the impaired activity of lymphocytes. These data suggest that decreased lymphocyte function might be used as a predictor of LAHS, which has critical clinical significance in diagnosis and further understanding the pathogenesis of the disease.

Lymphoma-associated hemophagocytic syndrome in six dogs.

Hemophagocytic syndrome (HPS) is a clinicopathological entity characterized by histiocytic proliferation, with marked hemophagocytosis in the reticuloendothelial organs. HPS caused by lymphoma is termed lymphoma-associated hemophagocytic syndrome (LAHS), and there are few reports on canine and feline LAHS. The objective of this study was to examine the clinical, diagnostic, and clinicopathologic features of LAHS in six dogs. The diagnostic criteria of LAHS consisted of lymphoma, bicytopenia or pancytopenia in the blood, and increased hemophagocytosis in the reticuloendothelial organs. In one dog, an ocular form of lymphoma was recognized. A splenic form was recognized in two dogs, and a hepatosplenic form was recognized in three dogs. Immunophenotyping revealed T-cell origin in five dogs and B-cell origin in one dog by polymerase chain reaction for antigen receptor rearrangement analysis. Nonspecific esterase stain was performed to differentiate between neoplastic lymphocytes and hemophagocytes. All five dogs with T-cell lymphoma were diagnosed with large granular lymphocyte (LGL) lymphoma. In three cases, palliative therapy with glucocorticoids was conducted, while the other three cases received chemotherapy as well. The survival times for the three dogs with glucocorticoids only were 6, 6, and 10 days and were 30, 54, and 68 days for the three treated with anticancer therapy. The median survival time for the dogs was 20 days. This report indicates that canine LAHS is likely to be caused by LGL lymphoma, and it has an aggressive behavior and poor general prognosis, as seen in humans.

High concentration of miR-133 is a useful marker for the diagnosis of lymphoma- associated hemophagocytic syndrome.

BACKGROUND: Lymphoma associated hemophagocytic syndrome (LAHS) is one of the major adult secondary hemophagocytic lymphohistiocytosis (HLH). Early diagnosis and treatment contribute to improved outcome. No enlarge lymph nodes can often delay the diagnosis of underlying lymphoma. OBJECTIVE: To find out criteria distinguishing LAHS from HLH induced by benign diseases. METHODS: clinical characteristic and laboratory feature of 31 patients with HLH (10 benign disease-associated HLH and 21 LAHS) were analyzed retrospectively. RESULTS: No significantly differences were observed in the levels of LDH, IL-6, IL-10, TNF-α; however, the level of CRP (C reactive protein) and the mean level of sIL-R (soluble interleukin-2 receptor) were higher in patients with LAHS than those with benign disease associated disease associated HLH while ferritin levels were higher in benign disease associated HLH than in LAHS. Consequently, the serum sIL-2R/ferritin ratio of patients with LAHS was markedly higher than that of patients with benign disease associated HLH (0.33 ± 0.23 vs 5.82 ± 3.26, P= 0.0001). In addition, we found out that the mean level of miR-133 (microRNA-133) was significant higher in LAHS than in benign disease associated HLH (18.83 ± 10.44 vs 5.82 ± 3.26, P⩽ 0.0001). CONCLUSION: Serum miR-133 is a new very useful marker for diagnosing of LAHS, but it need further confirmation by further clinical studies.

A clinical study of 21 patients with hemophagocytic syndrome in 295 cases diagnosed with nasal type, extranodal nature killer/T cell lymphoma.

Nasal type, extranodal nature killer (NK)/T cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS) is a rare and fatal disorder with extremely poor prognosis. To investigate its clinical characteristics and risk factors, we retrospectively analyzed 295 patients with nasal type, extranodal nature killer/T cell lymphoma, of which 21 were diagnosed with hemophagocytic syndrome, with a cumulative incidence of 7.1%. The most frequently clinical characteristics were fever, lymphadenopathy, hepatosplenomegaly, pancytopenia, hyperferritinemia, liver dysfunction, hypertriglyceridemia, hypofibrinogenemia and evaluated lactate dehydrogenase (LDH) level. After a median follow-up of 27 months, the 2-year survival for the 295 patients was 74.6%. Significant difference for 2-year survival was found between patients with and without hemophagocytic syndrome (4.8% vs. 80.0%, P<0.001). After developing hemophagocytic syndrome, all patients survived no more than 3 months, with a median survival of 35 days. Risk factors for NK/T-LAHS were bone marrow (BM) involvement (P = 0.019; relative risk, 13.649; 95% confidence interval (CI): 1.538-121.103), hepatosplenomegaly (P = 0.003; relative risk, 9.616; 95%CI: 2.154-42.918), and elevated LDH level (>314U/L) (P = 0.038; relative risk, 6.293; 95%CI: 1.108-35.735). We conducted a risk model for all 295 patients based on the 3 adverse factors as follows: low risk (233 cases, 79.0%), no factor; intermediate risk (43 cases, 14.6%), one factor; high risk (19 cases, 6.4%), 2 or 3 factors. The probabilities for developing LAHS were 0.9% for low-, 14.0% for intermediate-, and 68.4% for high-risk group. Significant differences in the 3 risk groups were observed (P<0.001).

Anaplastic large cell lymphoma involving the urinary bladder: a case report and review of the literature.

T cell-derived malignant lymphoma is rarely detected as a bladder neoplasm. A literature review for anaplastic large cell lymphoma (ALCL) involving urinary bladder reveals only seven previously reported cases. Here, we report a case of a 59-year-old HIV-negative man with ALK-positive ALCL. He presented an unusual clinical course with initial consideration of adult onset Still's Disease (AOSD) due to his negative results searching for malignancy and infectious diseases. He rapidly developed macrophage activation (hemophagocytic) syndrome and experienced an unusual rapid disease progression and died in 39 days after onset of symptoms. Compared to previously reported cases, the current case of ALK-1-positive ALCL is a rare case with an unusual presentation. From this case, we learned that ALCL is one malignancy that should be considered and screened in patients with suspected AOSD. Also, T-cell lymphoma associated hemophagocytic syndrome should be considered in a patient with sustained corticosteroid-resistant spike fever, high serum ferritin, and rapid exacerbation of the disease course.

Lymphoma-associated hemophagocytic syndrome: An analysis of clinical features and survival of 27 cases from a single center in China / 肿瘤

Objective: To analyze the clinical features and treatment outcomes of patients with lymphoma-associated hemophagocytic syndrome (LAHS). Methods: Clinical data of 27 patients with LAHS diagnosed at Peking University Cancer Hospital between May 2007 and August 2014 were retrospectively analyzed. Results: Of the 27 patients, there were 18 males and 9 females, with a median age of 32 years (range: 14 to 77). At diagnosis of lymphoma, 17 patients (63.0%) were stage HI/IV, 8 (29.6%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 5≥2, 12 (46.2%) had International Prognostic Index (IPI) score 5≥3. The most common subtype was extranodal natural killer/T cell lymphoma (ENKTCL) (74.1%, 20/27). Three patients presented with hemophagocytic syndrome (HPS) at lymphoma diagnosis, while the other 24 patients developed HPS during lymphoma progression after failure of chemotherapy. The clinical features of HPS were persistent fever (100.0%), splenomegaly (88.9%), hepatomegaly (37.0%), lymph node enlargement (63.0%), cytopenia (100.0%), ferritin increased (92.6%), hypertriglyceridemia (55.6%), hypofibrinogenemia (55.6%), and hemophagocytosis in bone marrow (70.4%). After a median follow-up of 11.0 months (range: 0.3 to 66.0 months), 24 (88.9%) patients died, and 3 survived. The median overall survival (OS) after the diagnosis of lymphoma was 11 months, and the median OS after the diagnosis of HPS was 28 days. One patient receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) remained alive with complete remission for 53 months. Conclusion: The clinical manifestations of LAHS were complex, and the prognosis and survival time remain dismal. More effective therapeutic strategies should be develpoed, and allo-HSCT may provide survival benefts to LAHS.

Successful treatment with recombinant thrombomodulin for B-cell lymphoma-associated hemophagocytic syndrome complicated by disseminated intravascular coagulation.

We report here a 47-year-old male with the diagnosis of high-grade B-cell lymphoma and hemophagocytosis accompanying disseminated intravascular coagulation (DIC). Lymphoma-associated hemophagocytic syndrome (LAHS) is a life-threatening disorder, and LAHS secondary to B-cell lymphoma is relatively rare compared to that secondary to T- or NK/T-cell lymphoma in Western countries. T- or NK/T-cell LAHS is sometimes combined with DIC, which makes patients' outcomes even worse, but few reports of B-cell LAHS accompanying DIC has been published so far. We successfully treated a patient with this condition with recombinant thrombomodulin (rTM), a novel agent for DIC. We believe that rTM is a therapeutic option in cases with B-cell LAHS accompanying DIC.