毛细胞白血病

Hairy cell leukemia,past,present,furture by Yehonghui,The Fifth Affiliated Hospital of Sun Yat-sen University,Introduce,extremely rare form of leukemiamiddle aged menpancytopenia and splenomegalylong life span,history of HCL(1923-1953),Edward in 1923 described splenomegaly without lymphadenopathy pancytopenia with lymphocytosis and monocytopeniaGosselin in 1944-1953 3 distinctive subtype bone lesion cutaneous manifestation,history of HCL(1958-1974),named as hairy cell leukemiamicroscopic sign median mature lyphocyte cytoplasm pseudopods protruding serrated borderlymphoproliferative disorder,ACP and TRAPbiopsyelctron microscope,Bone marrow biopsy in HCL reticulin stain,predict clinic outcomesplenectomy 67% remained HCR after 6 month 5 years OS 61% chlorambucil,in 80s,interferon-alfa 300m u/m2 3time per week and lasted for one year side-effect 2-4-8 ORR 70% CR 8%,in 90s,Aetiology HTLV EBV HPV-B +5 del(5q13)Origin of HC CD19+CD20+CD22+SIg+ CD10- PCA-1Scretion TNF-alfa IL-6,in 90s,purine 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 therapy,Cladribine: recurrence rate 26%, median time 29 monthsSide effect: progressively worse response cumulative myelotoxic effect second tumor,In The New Era,Multi-colored Flow CytometryGene mutation BRAF-MEK-ERK pathwayImmunotherapy or targeted therapy,Expert consensus on diagnosis of B cell chroniclymphoproligerative disorders in China 2014,Rituximab,Expression 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%,Treatment algorithm,BRAF mutation,Tiacci in 2009 fist described in melanoma100% harbored BRAF V600E mutation orign?Vemurafenib inducing hairy cells apoptosis,Vemurafenib,phase 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 8-12w,HCL Variant,10% 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 aggressive,IgHV 4-34 rearrangement and othersMEK inhibitionClassified as a separate entity by WHO 2008,Future Direction,Optimizing therapy of relapsed patientsrole of MRD role of ongoing therapyBRAF-MEK-ERK pathway,Summary,rare 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,