New Treatment For The Treatment Of Chronic Lymphocytic Leukemia

Part I Evaluate the safety and efficacy of Ibrutinib in the treatment of relapsed and refractory CLLBackgroundChronic lymphocytic leukemia is a clonal proliferative disease of mature B lymphocytes.Clinically,it is mainly manifested as increased lymphocyte count in peripheral blood,enlarged liver,spleen and lymph nodes,and progressive bone marrow failure(anemia,decreased platelet count,etc.)in late stage.Chronic lymphocytic leukemia is the most common type of leukemia in Western countries,and its incidence in China is also increasing year by year.Although CLL usually manifests as a lazy course,it is still largely incurable in terms of existing treatments,and the prognosis is heterogeneous,especially for high-risk cytogenetic factors or recurrence.Patients with refractory CLL often do not have lasting relief.The emergence and development of B cell receptor pathway inhibitors has brought CLL standard treatment to a new level.Previous studies have shown that ibufibrate has achieved encouraging results and good tolerance in patients with relapsed and refractory CLL,and has an important impact on the standard treatment of CLL.Objective1.To Evaluation of Ibrutinib treatment of relapsed or refractory CLL,the overall response rate(ORR),progression-free survival(PFS),and so on.2.The safety and tolerability of relapsed or refractory CLL subjects after oral administration of Ibrutinib 420 mg QD was evaluated.MethodRetrospective analysis of clinical data of 20 patients with relapsed and refractory CLL who had relatively complete data on oral administration of ibrutinib420 mg QD in the multi-center of Henan Province(Affiliated Tumor Hospital of Zhengzhou University,First Affiliated Hospital of Henan University of Science and Technology,Nanyang Central Hospital,etc.)from October 2017 to March 2019.All patients were CLL diagnosed by flow cytometry immunophenotyping and were either ineffective or relapsed after ?1 previous treatment regimen.The treatment regimen is 420 mg once a day orally.For patients with high tumor burden,alkalization,hydration and allopurinol administration are given simultaneously.Patients with chronic viral hepatitis B are given antiviral treatment with entecavir dispersible tablets,and 28 days is a treatment.cycle.Patients were assessed for efficacy including total response rate(ORR),progression-free survival(PFS),and other efficacy assessments based on the revised IWCLL guidelines.The efficacy evaluation will be based on clinical and imaging assessments.Subjects with bone marrow involvement will require a bone marrow biopsy to confirm complete remission(CR)in the presence of evidence for imaging and clinical complete remission.Collect specific clinical data of patients treated with this regimen,and summarize their efficacy and safety.OutcomeFollow-up As of March 31,2019,a total of 20 patients with relapsed or refractory CLL were treated with ibufenib 420 mg QD orally.There were 11 male patients(55%)and 9 female patients(45%)with a median age of 63(32~86)years.There were 4 patients(20%)with 17p13.1 deletion,13q14.3/13q34 deletion patients(35%),11q22.3 deletion patients with 2 patients(10%),and +12 positive patients with 3 patients(15%).A total of 19 patients achieved partial response to lymphocytosis(PR-L)or better optimal response,including 4 patients with del(17p)or TP53 mutations,1 patient was ineffective,and ORR was 95%;all The median follow-up time was 7.3(2.5 to 17.2)months,17 patients continued the drug treatment at the time of data cutoff,and 2 patients were followed up to 4.8 months(effectiveness evaluation PR),5.8 months(effectiveness evaluation PR-L)The application was stopped due to disease progression(PD),and no patient has died of disease progression.The most common adverse reactions were pulmonary infection rate of 35%(7/20),hypertension rate of 25%(5/20),the incidence of rash was 15%(3/20),the incidence of atrial fibrillation is 15%(3/20),the incidence of neutropenia reduction is 15%(3/20),and the incidence of diarrhea is 5%(1/20),and incidence of hemorrhagic adverse events is 20%(4/20),of which the most common site of skin mucosal bleeding.ConclusionIbrutinib has good response rates and tolerance,including del(17p)or TP53 mutations in patients.Part II Clinical efficacy of low-dose methylprednisolone combined with rituximab and fresh frozen plasma in the treatment of 9patients of chronic lymphocytic leukemia with thrombocytopenia as the main manifestationObjective:To investigate the efficacy and safety of low-dose methylprednisolone combined with rituximab and fresh frozen plasma in the treatment of chronic lymphocytic leukemia with thrombocytopenia as the main manifestation.Methods:The treatment of chronic lymphocytic leukemia with thrombocytopenia as the main manifestation was treated with low-dose methylprednisolone combined with rituximab and fresh frozen plasma.Specifically: rituximab 375 mg/m2 on day 0,fresh frozen plasma 400 ml on day 0~4,methylprednisolone 40~80mg on day 1~5(specific dosage adjusted according to patient's condition),while protecting stomach,preventing fungi and virus infection.To collect the clinical data of patients with chronic lymphocytic leukemia with thrombocytopenia as the main clinical manifestation and to analyze the platelet recovery,efficacy and safety of patients.Results:A total of 9 patients with chronic lymphocytic leukemia treated with thrombocytopenia were enrolled in the study.Among them,5 patients with TP53 mutation had CR,3 patients had PR,1 patient had SD;4 patients had no TP53 mutation.1 case of CR,3 cases of PR;ORR: 8 cases(88.9%),CR: 2 cases(22.2%).After 1 course of treatment,the median platelet count of 9 patients increased from12(3~21)� 109 / L to 48(27 ~ 91)� 109 / L(t = 6.040,P < 0.001),2 patients after 2courses of platelets After returning to normal,platelet returned to normal in 5patients after 4 courses of treatment,and platelet still did not return to normal after 2courses of treatment,but it was significantly higher than before treatment [median126(63~179)�109/L,t=11.326 P <0.001],has reached a safe level.Conclusions:Patients with chronic lymphocytic leukemia who have thrombocytopenia as the main clinical manifestation have difficulty in clinical treatment.Conventional chemotherapy can lead to further reduction of platelets and increased risk of bleeding.Low-dose methylprednisolone combined with rituximab and fresh frozen plasma regimen are effective in treating such patients with few side effects and can be used as a first-line option.