资源描述
Hairy cell leukemia,past,present,furture by Yehonghui,1,Introduce,extremely rare form of leukemiamiddle aged menpancytopenia and splenomegalylong life span,2,history of HCL(1923-1953),Edward in 1923 describedsplenomegaly without lymphadenopathypancytopenia with lymphocytosis and monocytopeniaGosselin in 1944-1953 3 distinctive subtypebone lesioncutaneous manifestation,3,4,5,history of HCL(1958-1974),named as hairy cell leukemiamicroscopic signmedian mature lyphocytecytoplasm pseudopods protruding serrated borderlymphoproliferative disorder,6,7,ACP and TRAPbiopsyelctron microscope,8,Bone marrow biopsy in HCL reticulin stain,9,10,predict clinic outcomesplenectomy 67% remained HCR after 6 month 5 years OS 61%chlorambucil,11,in 80s,interferon-alfa 300m u/m2 3time per week and lasted for one yearside-effect2-4-8ORR 70% CR 8%,12,in 90s,Aetiology HTLV EBV HPV-B+5 del(5q13)Origin of HC CD19+CD20+CD22+SIg+ CD10- PCA-1Scretion TNF-alfa IL-6,13,in 90s,purine nucleoside analogsPentostatin 4mg/m2/2W total 8 timesORR 79% CR 76%Cladribine 0.1mg/Kg/day for 7daysORR 97% CR 85%not identical therapy,14,15,Cladribine: recurrence rate 26%, median time 29 monthsSide effect: progressively worse responsecumulative myelotoxic effectsecond tumor,16,In The New Era,Multi-colored Flow CytometryGene mutation BRAF-MEK-ERK pathwayImmunotherapy or targeted therapy,17,18,Expert consensus on diagnosis of B cell chronic lymphoproligerative disorders in China 2014,19,20,Rituximab,Expression of CD20 antigenAs a single agentNew 375mg/m2 weekly 4-8 CR 64%Replase 375mg/m2 weekly 4-8 CR 53% As a combination New 375mg/m2 weekly 4-8 CR 100%,21,22,Treatment algorithm,23,BRAF mutation,Tiacci in 2009 fist described in melanoma100% harbored BRAF V600E mutation orign?Vemurafenib inducing hairy cellsapoptosis,24,Vemurafenib,phase 2 multicenter studyearly replase, refractory to PA,bone marrowhypoplasia at the time of relapse,severe sideeffect960 mg twice daily for a minimum of 8 weeks ORR 96-100% medium response time 8-12w,25,26,27,28,29,30,HCL Variant,10% of HCL casesSimilarity: age gender splenomegaly anemia etc.morphologyDissimilarity: higher white blood cell countlack of monocytopeniaabsent of Annex-1 CD25 BRAF V600Eless durable responses to PAmore aggressive,31,32,33,IgHV 4-34 rearrangement and othersMEK inhibitionClassified as a separate entity by WHO 2008,34,Future Direction,Optimizing therapy of relapsed patientsrole of MRD role of ongoing therapyBRAF-MEK-ERK pathway,35,Summary,rare cas classified as B-CLPD in WHO 2008Clinical manifestations:splenomegaly pancytopenia bone lesion skin lesionLaboratory examination: blood bone marrow biopsyMFC molecular biologyDifferential Diagnosis with other B-CLPDMyelofibrosis and Hypersplenism,36,Treatment strategies: purine nucleoside analogsImmunotherapy or targeted therapynormal life expectation,37,Timeline,38,Thank you for your attention,39,
展开阅读全文