There is also an expert consensus on the diagnosis and treatment of lymphoma associated hemophagocytic syndrome.
2018-07-13
Hemophagocytic syndrome (HPS) is also known as Haemophilus lymphohistiocytosis (HLH). Lymphoma is one of the important causes of HLH. Lymphoma related HLH is a primary cause of HLH or HLH in lymphoma treatment. According to the time difference, it is classified as "lymphoma induction." There are two main categories of HLH and HLH during chemotherapy.
In order to improve the understanding and understanding of lymphoma related HLH in Department of Hematology doctors and oncologists, China Cancer Association lymphoma Specialized Committee organization related experts have formulated the Chinese expert consensus on the diagnosis and treatment of lymphoma related hemophagocytic syndrome.
diagnostic criteria
HLH diagnostic criteria for lymphoma
At present, there is no universally recognized diagnostic standard for lymphoma HLH. At this stage, the HLH-2004 guidelines for the diagnosis of HLH are still recommended by the international organization cell association in 2004. Therefore, on the basis of a clear pathological diagnosis of lymphoma, the HLH diagnosis of lymphoma associated with 5 of the following 8 indicators could be established: fever: fever: temperature > 38.5, continuous > 7d; splenomegaly; (3) hemoglobin (involving two or three lines in peripheral blood): hemoglobin < 90g/L, platelet < 100 10. 9/L, neutrophils < 1 x 109/L and non bone marrow hematopoiesis; (4) hypertriglyceridemia and / or hypofibrinogen: three acyl glycerol > 3mmol/L or higher than 3 standard deviations of the same age, fibrinogen <1.5g/L or lower than the standard deviation of the same age; (5) in bone marrow, spleen, liver, or lymph nodes To find hemophagocytic cells; (6) serum ferritin increased: ferritin > 500 g/L; NK cell activity was reduced or absent; soluble interleukin -2 receptor (sCD25) increased.
Supplementary description of HLH diagnostic criteria for lymphoma
First, although HLH is classified into different types according to etiology, diagnostic criteria for various subtypes have not been widely accepted. Therefore, the guideline of HLH-2004 diagnosis is the principle that should be followed in clinical diagnosis of HLH.
Secondly, there are many overlapping overlaps in the clinical features of lymphoma itself and HLH (such as fever, hemocyte reduction, hepatomegaly, elevated ferritin, high lactate dehydrogenase and so on). Therefore, it is difficult to judge whether lymphoma patients are accompanied by HLH, which will cause the diagnosis of enlargement. The finding of hemophagocytosis in lymphoma patients may be highly suggestive of HLH.
And because many of the clinical and laboratory findings of HLH can be explained by lymphocytic and histiocytic infiltration of tissue and hypercytokine, high throughput detection of HLH related cytokine profiles can help identify whether lymphoma patients combine HLH at the same time. The significant increase of sCD25 / serum ferritin ratio is also one of the means to diagnose lymphoma related HLH.
Treatment
1.HLH-94 treatment program:
The standard HLH regimen currently widely used is either HLH-94 or HLH-04, which was formulated by the International Association of Histocyte Organizations in 1994 and revised in 2004. The induction therapy of HLH-94 includes dexamethasone, etoposide (VP-16), and intrathecal methamphetamine and dexamethasone.
HLH-04 is based on HLH-94's revise, which uses the loop A (CsA) in advance to the induction period and VP-16 at the same time. The dose of VP-16 in the induction protocol was 150mg/m2 per time. If the weight of the patient is less than 10kg, the dose of VP-16 can also be calculated by 5mg/kg.
Due to the relatively low demand and tolerance of teenager / adult to etoposide, the age related adjustment for the use of VP-16 was made, 75 to 150mg/m2 under 15 years of age, 75 to 100mg/m2 in 15~39 year old patients and 50 to 75mg/m2 for patients over 40 years of age. Reducing the dosage of VP-16 in elderly patients allows patients to be better tolerated during treatment and does not affect efficacy. Dexamethasone: first to 2 weeks 10mg m-2 / D-1, third to 4 weeks 5mg m-2 D-1, fifth to 6 weeks 2.5mg m-2 D-1, seventh weeks 1.25mg m-2 D-1, eighth weeks to stop drugs, oral or intravenous injection, the latter is the first choice for initial treatment.
Treatment options similar to HLH-94 (adjusted dose and medication time) are often individualized in patients with different conditions. According to the prospective clinical research results of the HLH-94 and HLH-04 therapy and the latest opinion of the international organization cell association, the use of the HLH-04 regimen is not recommended as an inducer for the lymphoma related HLH patients.
2.DEP programme:
The DEP regimen is a combination chemotherapy consisting of liposomal doxorubicin, VP-16 and methylprednisolone. The initial dose was liposome doxorubicin 25mg / m-2 D-1 D1, VP-16 10mg m-2 D-1 D1 (the age adjustment principle can be referred to as the induction therapy), methylprednisolone 15mg kg-1 D-1, 3, 7, 10 to the next course of treatment. The regimen was repeated every 2 weeks, and the initial dose of methylprednisolone could be changed to 2mg kg-1 D-1 when repeated second times and later. The DEP protocol can be used in the initial induction therapy for lymphoma related HLH, and can also be used in refractory patients with HLH-94 response.
Stratified therapy strategy
Whether the treatment of lymphoma-associated HLH should be targeted at HLH or lymphoma first is not yet evidence-based and should be determined according to the patient's different conditions.
For patients with lymphoma-induced HLH, HLH-94 or DEP regimens are recommended to control HLH before initiating tumor-specific therapy. Once the primary control is obtained, HLH should be actively transferred to the primary treatment (the standard lymphoma chemotherapy), and the conditional patients can consider the hematopoietic stem cell transplantation (HSCT). For patients with "HLH" in chemotherapy,
