毛细胞白血病课件.ppt

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1、Hairy cell leukemiapast,present,furture by Yehonghui1Introduceextremely rare form of leukemiamiddle aged menpancytopenia and splenomegalylong life span2history of HCL(1923-1953)Edward in 1923 described splenomegaly without lymphadenopathy pancytopenia with lymphocytosis and monocytopeniaGosselin in

2、1944-1953 3 distinctive subtype bone lesion cutaneous manifestation 345history of HCL(1958-1974)named as hairy cell leukemiamicroscopic sign median mature lyphocyte cytoplasm pseudopods protruding serrated borderlymphoproliferative disorder67ACP and TRAPbiopsyelctron microscope 8Bone marrow biopsy i

3、n HCL reticulin stain910predict clinic outcomesplenectomy 67%remained HCR after 6 month 5 years OS 61%chlorambucil11in 80sinterferon-alfa 300m u/m2 3time per week and lasted for one year side-effect 2-4-8 ORR 70%CR 8%12in 90sAetiology HTLV EBV HPV-B +5 del(5q13)Origin of HC CD19+CD20+CD22+SIg+CD10-P

4、CA-1Scretion TNF-alfa IL-6 13in 90spurine nucleoside analogsPentostatin 4mg/m2/2W total 8 times ORR 79%CR 76%Cladribine 0.1mg/Kg/day for 7days ORR 97%CR 85%not identical therapy1415Cladribine:recurrence rate 26%,median time 29 monthsSide effect:progressively worse response cumulative myelotoxic effe

5、ct second tumor16In The New EraMulti-colored Flow CytometryGene mutation BRAF-MEK-ERK pathwayImmunotherapy or targeted therapy1718Expert consensus on diagnosis of B cell chroniclymphoproligerative disorders in China 20141920RituximabExpression of CD20 antigenAs a single agent New 375mg/m2 weekly 4-8

6、 CR 64%Replase 375mg/m2 weekly 4-8 CR 53%As a combination New 375mg/m2 weekly 4-8 CR 100%2122Treatment algorithm23BRAF mutationTiacci in 2009 fist described in melanoma100%harbored BRAF V600E mutation orign?Vemurafenib inducing hairy cells apoptosis24Vemurafenibphase 2 multicenter studyearly replase

7、,refractory to PA,bone marrow hypoplasia at the time of relapse,severe side effect960 mg twice daily for a minimum of 8 weeks ORR 96-100%medium response time 8-12w252627282930HCL Variant10%of HCL casesSimilarity:age gender splenomegaly anemia etc.morphologyDissimilarity:higher white blood cell count

8、 lack of monocytopenia absent of Annex-1 CD25 BRAF V600E less durable responses to PA more aggressive313233IgHV 4-34 rearrangement and othersMEK inhibitionClassified as a separate entity by WHO 200834Future DirectionOptimizing therapy of relapsed patientsrole of MRD role of ongoing therapyBRAF-MEK-E

9、RK pathway35Summaryrare cas classified as B-CLPD in WHO 2008Clinical manifestations:splenomegaly pancytopenia bone lesion skin lesionLaboratory examination:blood bone marrow biopsy MFC molecular biologyDifferential Diagnosis with other B-CLPD Myelofibrosis and Hypersplenism 36Treatment strategies:purine nucleoside analogs Immunotherapy or targeted therapynormal life expectation37Timeline3839

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