Overview
Large granular lymphocytic leukemia (LGLL) is a lymphoproliferative disease, with LGL infiltration in peripheral blood and bone marrow, hepatosplenomegaly, and cytopenia. Both T-LGLL and CLPD-NK are indolent disease and share similar biology and clinical course, and treated under the same strategy. So the investigators put them together as LGLL. The investigators used TPM regimen (thalidomide + prednison + methotrexate ) to treat LGLL since 2013, and 18/20 patients (90%) obtained clinical response, including 80% complete response. Adverse events (AE) of grade 3 and above are rare and safe. Therefore, the investigators designed this multicenter clinical trial to validate the efficacy of the TPM regimen in symptomatic T-LGLL and CLPD-NK.
Description
Because LGLL has continuously activated cytotoxic T lymphocytes, immunosuppressive therapy is the standard first-line therapy for T-LGLL and CLPD-NK. Previous studies showed that the overall response rate (ORR) of first-line oral immunosuppressants ranged from 21% to 85% (median: 50%). Both methotrexate and cyclosporine A are LGLL first-line treatment options, but the CR rate of methotrexate is only 21%, while the CR rate of CsA is less than 5%. There is insufficient evidence for the treatment of LGLL with prednisone and other glucocorticoids, but it can reduce RA-related inflammation and increase granulocyte levels. The TPM regimen was designed by the investigators. A pilot prospect observation showed that 18/20 (90%) patients obtained response, including 80% CR. This study is a prospective multiple center clinical trail to evaluate the efficacy of TPM regimen in the treatment of symptomatic LGLL. Eligible patients choose the initial treatment plan: thalidomide 50-100mg qn+ prednisone 0.5-1mg / kg qod +methotrexate 10mg / m2 / week. Four months is one course. Maximum three courses will be given if there is a response and thalidomide maintenance will be for another year.
Eligibility
Inclusion Criteria:
- The gender of the patient is not limited, and the age is 18 years old;
- Must meet diagnostic criteria of T-LGLL or CLPD-NK according to WHO 2016 version;
- The patient is treatment naive or received single methotrexate less than 4 weeks and without response. If relapsed or refractory patients, the patients must be naive for both thalidomide and methotrexate.
- With LGLL treatment indications, it mainly includes (meets at least one of the following conditions):
- ANC <0.5 10^9 / L
- HGB <100g / L or need red blood cell infusion to maintain
- PLT <50 10^9 / L
- Combining autoimmune diseases that require treatment
- symptomatic splenomegaly
- Severe B symptoms
- Pulmonary hypertension.
- ECOG performance status score is 0-2;
- The patient's expected survival time is 6 months.
Exclusion Criteria:
- Unable to understand or follow the research procedure;
- Co-occurrent malignant tumors that has to be treated or course the symptom;
- Other serious diseases, such as liver, kidney, heart, lung, nerve or metabolic diseases, may impede the ability of patients to tolerate methotrexate, cyclophosphamide or cyclosporin A;
- ALAT / ASAT or alkaline phosphatase> 3 times the normal value;
- Creatinine clearance <60ml / min;
- Serological evidence of active infection of HIV, hepatitis C or hepatitis B;
- Ineffective contraception;
- Positive pregnancy test;
- Pregnant women.