Clinical Study On 20 Cases Of T-cell Lymphoma Associated Hemophagocytic Syndromes(LAHS)

BACKGROUNDHemophagocytic lymphohistiocytosis (HLH) is a lifethreatening condition characterized by uncontrolled hyperinflammation on the basis of various inherited or acquired immune deficiencies. Cardinal symptoms are prolonged fever, hepatosplenomegaly and cytopenias. Central nervous system (CNS) symptoms are common. Biochemical markers include elevated triglyceride and ferritin, high levels of the chain of the soluble interleukin-2 receptor and low fibrinogen.Impaired function of natural killer (NK) cells and cytotoxic T-cells (CTL) is a characteristic of all forms of HLH. Most patients with acquired HLH have no known underlying immune deficiency. Both acquired and genetic forms are triggered by infections, mostly viruses, or other stimuli. HLH also occurs as a complication of rheumatic diseases (macrophage activation syndrome) and of malignancies. Awareness of its clinical symptoms and diagnostic criteria is important to starting prompt life-saving therapy. While HLH and its genetic defects have provided insight into the mechanisms of host defense, our understanding of its complex pathophysiology still remains incomplete.T-cell lymphoma is the special malignant type of non-Hodgkin's lymphoma. The diagnosis and the treatment were usually troublesome for physician in clinical practice. The lymphoma associated hemophagocytic syndromes (LAHS) has a rapidly deteriorating course in approximated half of the patients.The outcome is usually poor, response to treatment unsatisfactory, early bone marrow ablative chemotherapy with allograft would be a better option than conventional chemotherapy or immunosuppression. Differential diagnosis with malignant histocytosis(MH) is usually very difficult at clinical, cellular morphological and pathohistiogical aspects. The immediate aim in the treatment of any patient with HLH is to suppress the severe hyperinflammation that is responsible for the life-threatening symptoms. Another aim is to kill pathogen-infected antigen-presenting cells and thus remove the stimulus for the ongoing but ineffective activation of T cells.Marked cytopenias, coagulation problems and CNS symptoms should receive treatment according to the present HLH protocol .Hyperinflammation can be treated with corticosteroids, immunoglobulin infusions, which are cytotoxic for lymphocytes and inhibit expression of cytokines and differentiation of dendritic cells. The pathogenesis, clinical features, laboratory findings, treatment and prognosis of HPS are reviewed in this article. Our Objectives to explore the manifestation, laboratory finding ,diagnosis treatment and survival of lymphoma associated hemophagocytic syndromes (LAHS).METHODSWe observed 20 cases of lymphoma associated hemophagocytic syndromes (LAHS) from 63 cases of T-cell lymphomas in our hospital during the period from January 2000 to July 2006, and collected information about LAHS: classification, manifestation, laboratory finding and survival. 19 cases were under our follow-up for 1 year since the final diagnosis.RESULTSThe median age for this disease was 37 year. The median life span was 39 days (range 21 days to 10 months). The initial manifestations included fever (19/20),splenohepatomegaly (18/20), and cytopenia of at least 2 cell lines in all patients. Only 15% patients had enlargement of lymphonodes, which was suggested to be infrequent in LAHS. Other manifestation included skin rash or phymata, pruritus, jaundice, abdominal pain, rhinorrhagia, puffiness, diarrhea,and ulcus. Immatural T-cell infiltration in bone marrow was detected in 75% (15/20) cases. High level of LDH, elevated β2-microglobulin were detected. Chromosome disorder of [der(21)(p11), -22] was detected in 3 cases. We also found that 2 cases which underwent plasmapheresis got much better after chemotherapy. 19 cases were under our follow-up. 17 patients could not survival longer than 6 months. The 6-month overall survival (OS) for LAHS was merely 2 of all 20. Furthermore, nobody survived more than 1 year, which indicated the poor prognosis of LAHS. There were 11 out of 20 cases had received trial chemotherapy including liposomal Doxorubicin, L-asparaginase, velcade, autologous bone marrow transplantation, or plasmapheresis before chemotherapy. The median survival time prolonged obviously from 2 months up to 8 months, which suggested the encouraging efficiency of these methods. The patients were reclassified according to the World Health Organization classification system. Clinical data, including age, gender, clinical staging, and follow-up, were scrutinized.ConclusionsHPS is a rare disease with complex clinical presentation. The lymphoma associated hemophagocytic syndromes (LAHS) patients often undergo an aggressive clinical course resulting in (?) poor prognosis. Early diagnosis and prompt treatment is the key point for prognosis. The management of is usually based on the administration of high doses of corticosteroids and immunoglobulin infusions to control hyperinflammation and to reverse the clinical and laboratory symptoms. CSA has also proven effective in treating severe or corticosteroid resistant cases. Trial chemotherapy including liposomal Doxorubicin, L-asparaginase, velcade, autologous bone marrow transplantation, or plasmapheresis before chemotherapy, prolonged themedian survival time, suggesting the encouraging efficiency of these methods.