毛细胞白血病课件

Hairycellleukemiapast,present,furture by Yehonghui1Hairy cell leukemiapast,presenIntroduceextremely rare form of leukemiamiddle aged menpancytopenia and splenomegalylong life span2Introduceextremely rare form ohistoryofHCL(1923-1953)Edward in 1923 described splenomegaly without lymphadenopathy pancytopenia with lymphocytosis and monocytopeniaGosselin in 1944-1953 3 distinctive subtype bone lesion cutaneous manifestation 3history of HCL(1923-1953)Edwar4455historyofHCL(1958-1974)named as hairy cell leukemiamicroscopic sign median mature lyphocyte cytoplasm pseudopods protruding serrated borderlymphoproliferative disorder6history of HCL(1958-1974)named77ACP and TRAPbiopsyelctron microscope 8ACP and TRAP8Bone marrow biopsy in HCL reticulin stain9Bone marrow biopsy in HCL reti1010predict clinic outcomesplenectomy 67%remained HCR after 6 month 5 years OS 61%chlorambucil11predict clinic outcome11in80sinterferon-alfa 300m u/m2 3time per week and lasted for one year side-effect 2-4-8 ORR 70%CR 8%12in 80sinterferon-alfa 12in90sAetiology HTLV EBV HPV-B +5 del(5q13)Origin of HC CD19+CD20+CD22+SIg+CD10-PCA-1Scretion TNF-alfa IL-6 13in 90s13in90spurine 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 therapy14in 90spurine nucleoside analog1515Cladribine:recurrence rate 26%,median time 29 monthsSide effect:progressively worse response cumulative myelotoxic effect second tumor16Cladribine:recurrence rateInTheNewEraMulti-colored Flow CytometryGene mutation BRAF-MEK-ERK pathwayImmunotherapy or targeted therapy17In The New EraMulti-colored Fl1818ExpertconsensusondiagnosisofBcellchroniclymphoproligerativedisordersinChina201419Expert consensus on diagnosis 2020RituximabExpression of CD20 antigenAs a single agent New 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%21RituximabExpression of CD20 an2222Treatmentalgorithm23Treatment algorithm23BRAFmutationTiacci in 2009 fist described in melanoma100%harbored BRAF V600E mutation orign?Vemurafenib inducing hairy cells apoptosis24BRAF mutationTiacci in 2009 fVemurafenibphase 2 multicenter studyearly replase,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 8-12w25Vemurafenibphase 2 multicente26262727282829293030HCLVariant10%of HCL casesSimilarity:age gender splenomegaly anemia etc.morphologyDissimilarity:higher white blood cell count lack of monocytopenia absent of Annex-1 CD25 BRAF V600E less durable responses to PA more aggressive31HCL Variant10%of HCL cases3132323333IgHV 4-34 rearrangement and othersMEK inhibitionClassified as a separate entity by WHO 200834IgHV 4-34 rearrangement and otFutureDirectionOptimizing therapy of relapsed patientsrole of MRD role of ongoing therapyBRAF-MEK-ERK pathway35Future DirectionOptimizing thSummaryrare 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 36Summaryrare cas classified as Treatment strategies:purine nucleoside analogs Immunotherapy or targeted therapynormal life expectation37Treatment strategies:purine nTimeline38Timeline38Thank you for your Thank you for your Thank you for your Thank you for your attentionattentionattentionattention39Thank you for your attention39