종양 혈액암 ( 종양 ) (Hematlogic Malignancies) 양성종양 악성종양 악성종양 ( 질환 ) 암 고형암 : 고형장기발생악성질환 혈액암 : 골수또는림프조직에서발생

악성림프종 (Lymphoma) 호지킨병 [ 림프종 ] (Hodgkin s Disease [Lymphoma]) HD 비호지킨림프종 (Non-Hogkin s Lymhoma) NHL

형질세포질환 MGUS : Monoclonal Gammopathy of Undetermined Significance Plasmacytoma Multiple myeloma (MM) Asymptomatic; smoldering; Stage I Symptomatic; Stage II, III Waldenstrom s macroglobulinemia Amyloidosis POEM syndrome, Plasma cell leukemia

만성골수증식성질환 (CMPD) 진성적혈구증다증 (PV) Polycythemia vera 진성고혈소판증 (ET) Essential thrombocytopenia 특발성골수섬유화증 (IMF) Idiopathic myelofibrosis 만성골수구성백혈병 (CML) Chronic myelocytic leukemia

골수이형성증후군 (MDS) Myelodysplastic syndrome RA : refractory anemia ( 불응성빈혈 ) RARS : refractory anemia with ringed sideroblasts RAEB : refractory anemia with excess of blasts RAEB-T : RAEB in transformation CMML : chronic myelomonocytic leukemia

Bases of classification Morphology : most important part but sometimes not objective Immunophenotype : lineage, objective, target (ex. CD20) Genetic abnormalities : objective Specific : BCR-ABL, PML-RARA, Characteristic but not specific : MYC, CCND, BCL2 rearrangement, JAK2 mutation Prognostic : TP53 mutation or FLT3-ITD Clinical features : age, nodal versus extranodal presentation, specific anatomic site and history of cytotoxic and other therapies Provisional entities, borderline categories

WHO Classification 2001 2008

WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (2008) I. Myeloid neoplasms II. Acute leukemia of ambiguous lineage III. Lymphoid neoplasms IV. Histiocytic and dendritic cell neoplasms

WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues (2008) I. Myeloid neoplasms 1. Myeloproliferative neoplasms (MPN) 2. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 3. Melodysplastic/Myeloproliferative neoplasms (MDA/MPN) 4. Myelodysplastic syndrome (MDS) 5. Acute myeloid leukemia (AML) and related precursor neoplasms

1. Myeloproliferative neoplasms (MPN) 1) Chronic myelogenous leukemia, BCR-ABL 1 positive 2) Polycythemia vera 3) Primary myelofibrosis 4) Essential thrombocythemia 5) Chronic neurophilic leukemia 6) Chronic eosinophilic leukemia, NOS (CEL/hypereosinophilic synd.) 7) Mastocytosis 1 Cutaneous mastocytosis 2 Systemic mastocytosis 3 Mast cell leukemia 4 Mast cell sarcoma 5 Extracutaneous matocytoma 8) Myeloproliferative neoplasm, unclassifiable

2. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 1) Myeloid and lymphoid neoplasms with PDGFRA rearrangement 2) Myeloid neoplasms with PDGFRB rearrangement 3) Myeloid and lymphoid neoplasms with FGFR1 rearrangement

3. Melodysplastic/Myeloproliferative neoplasms 1) Chronic myelomococytic leukemia 2) Atypical chronic myeloid leukemia, (BCR-ABL1 negative) 3) Juvenile myelomonocytic leukemia 4) Myelodysplastic/Myeloproliferative neoplasms, unclassifiable 1) Refractory anemia with ring sideroblasts associated with marked thrombocytosis

4. Myelodysplastic syndrome 1) Refractory cytopenia with unilineage dysplasia 1) Refractory anemia 2) Refractory neutropenia 3) Refractory thrombocytopenia 2) Refractory anemia with ring sideroblasts 3) Refractory cytopenia with multineage dysplasia 4) Refractory anemia with excess blasts I, II 5) Myelodysplastic syndrome associated with isolated del(5q) 6) Myelodysplastic syndrome, unclassifiable 7) Childhood myelodysplastic syndrome 1) Refractory cytopenia of childhood

5. Acute myeloid leukemia (AML) and related precursor neoplasms 1) AML with recurrent genetic abnormalities 2) AML with myelodysplasia-related changes 3) Therapy-related myeloid neoplasms 4) Acute myeloid leukemia, NOS 5) Myeloid sarcoma 6) Myeloid proliferations related to Down syndrome 7) Blastic plasmacytoid dendritic cell neoplasm

II. Acute leukemias of ambiguous lineage ( 모호한, 애매한, 두가지이상의뜻이있는 ) 1. Acute undifferntiated leukemia 2. Mixed phenotype acute leukemia with t(9;22)(q34;q11.2); BCR-ABL1 3. Mixed phenotype acute leukemia with t(v;11q23); MLL rearranged 4. Mixed phenotype acute leukemia, B/myeloid, NOS 5. Mixed phenotype acute leukemia, T/myeloid, NOS 6. Natural killer (NK) cell lymphoblastic leukemia/lymphoma

III. Lymphoid neoplasms 1. Precursor lymphoid neoplasms 2. Mature B-cell neoplasms 3. Mature T-cell and NK-cell neoplasms 4. Hodgkin Lymphoma 5. Post-transplant lymphoproliferative disorders (PTLD) IV. Histiocytic and dendritic cell neoplasms

1. Precursor lymphoid neoplasms 1) B lymphoblastic leukemia/lymphoma 1 2 B lymphoblastic leukemia/lymphoma, NOS B lymphoblastic leukemia/lymphoma, with recurrent genetic abnormalities a. B lymphoblastic leukemia/lymphoma with t(9;22)(q34;q11.2); BCR-ABL1 b. B lymphoblastic leukemia/lymphoma with t(v;11q23); MLL rearranged c. B lymphoblastic leukemia/lymphoma with t(12;21)(p13;q22); TEL-AML1(ETV6-RUNX1) d. B lymphoblastic leukemia/lymphoma with hyperdiploidy e. B lymphoblastic leukemia/lymphoma with hypodiploidy (hypodiploid ALL) f. B lymphoblastic leukemia/lymphoma with t(5;14)(q31;q32); IL3-IGH g. B lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3); E2A-PBX1(TCF3-PBX1) 2) T lymphoblastic leukemia/lymphoma

2. Mature B-cell neoplasms 1) Chronic lymphocytic leukemia/small lymphocytic lymphoma 2) B-cell prolymphocytic leukemia 3) Splenic marginal zone lymphoma 4) Hairy cell leukemia 5) Splenic B-cell lymphoma/leukemia, unclassifiable 1 Splenic diffuse red pulp small B-cell lymphoma 2 Hairy cell leukemia-variant

각론 개별혈액종양질환의설명

AML 골수세포의악성화로백혈병세포가증식하고말초혈액에서백혈구가증가하며전신장기에침윤할수있음. 정상혈구세포의생산은감소. 증상 빈혈 감염 출혈 진단 CBC BM : 세포표지자검사 염색체검사, 분자생물학적검사

AML 치료 Chemotherapy : Induction CT : anthracycline + Ara-C (AI, AD) Consolidation Supportive care Stem cell transplantation APL [M3, t(15;17)] ATRA, arsenic trioxide + chemotherapy

치료반응 Hematologic response Complete remission : 5% BM : blast < 5% with count 500 nucleated cells ANC (absolute neutrophil count) : > 1,000/uL Platelet : > 100,000/uL Cytogenetic remission : 1 ~ 0.5 % Chromosome analysis, FISH Molecular remission : 1/10 4 ~ 10 6 PCR : PML-RARA,

CML 증상 무증상 ( 건진에서발견 ) 복부증상 : Splenomegaly 진행 : accelerating, blastic phase acute leukemia 진단 CBC BM Philadelphia 염색체, t(9;22), bcr-abl fusion gene

치료 Glivec 2 nd generation TKI Dasatinib, Nilotinib etc Stem cell transplantation Other chemotherapy, IFN Response Hematologic Cytogenetic : Ph, FISH (bcr-abl) Molecular : RT-PCR (bcr-abl)

3 개월 18 개월 12 개월 6 개월

MDS ( 골수이형성증후군 ) 조혈세포의이형성 (dysplastic) 변화로효과적인조혈이안됨. 골수세포의수는증가하나정상적인혈액세포는감소함. 증상 : Pancytopenia 연관증상 : 빈혈, 출혈, 감염 노년층 진단 : CBC BM : 필수 염색체, 분자생물학

Low : 0 Int-1 : 0.5-1.0 Int-2 : 1.5-2.0 High : 2.5 Very low : 0 Low : 1 Intermediate : 2 High : 3-4 Very high : 5 Cytogenetics : Good = normal, -Y alone, del(5q) alone, del(20q) alone ; Poor = complex ( 3 abnormaities) or chr. 7 anormalies ; Intermediate = other abnormalities Cytopenia : neutrophil < 1,800/mcL, Platelet < 100,000 mcl, Hb < 10g/dL RBC transfusion requirement = having 1 RBC every 8 weeks over a 4 months period

치료 대증요법 : 수혈, 항생제 Erythropoietin, G-CSF Chemotherapy : Vidaza, Dacogen : 반응평가 Anti-leukemic agents isolated del(5q) : lenalidomide Stem cell transplantation

MDS/MPN CMML Atypical CML (acml) JMML MDS/MPN, U 진단 : BM 치료 : CT, SCT, 대증요법

MPN (Myeloproliferative Neoplasms) PV : 적혈구증가 ET : 혈소판증가 IMF : 골수섬유화, 골수외조혈 ( 간, 비장 ) CML : 백혈구증가 진단 : CBC, BM, JAK2 mutation 치료 : HUA, IFN, anagrelide, SCT

악성림프종 진단 : biopsy HD, NHL Subtype : B, T cell; precursor, mature Staging : Ann Arbor stage Stage I, II, III, IV Imaging studies BM CT, MRI, PET

치료 항암화학요법 방사선치료 조혈모세포이식 : 자가, 동종 치료반응판정 CR PR

ALL 소아 : 성인 ALL : Lymphoblastic lymphoma Chemotherapy CNS prophylaxis Maintenance chemptherapy Stem cell transplantation

CLL CLL : SLL(Small lymphocytic lymphoma) 노년층 서양 : 가장흔한백혈병 치료 Wait and see Chemotherapy SCT

형질세포질환 MGUS : 경과관찰 Plasmacytoma Solitary Extramedullary Multiple Myeloma Waldenstrom s macroglobulinemia Lymphoplasmocytic lymphoma Amyloidosis POEM syndrome Plasma cell leukemia

MM ( 다발성골수종 ) 증상 : CRAB Hypercalcemia Renal failure Anemia Bone involvement 진단 : CBC M protein : PEP, FLC BM Bone involvements : X-ray, MRI, bone scan

치료 Plasmacytoma : single RT Asymptomatic MM : wait and see Symptomatic MM Transplantation eligible Induction Chemotherapy Autologous SCT : single or tandem Allogeneic SCT Transplantation ineligible Palliative CT RT Supportive care

향후전망 분류법의변화 WHO classifcation 진단방법의발전 유전자 분자생물학 치료법의변화 Target therapy