LEUKEMIA Leukemia n n the most common childhood

LEUKEMIA

Leukemia n n the most common childhood cancer counting for 33% of pediatric malignancy 병형 Acute lymphocytic 비율(%) 70~80 비율(한국, %) 60 Acute myelocytic 10~20 30 Acute monocytic 3~8 5 Chronic myelocytic 2~5 3 2 2 기타

급성림프구성 백혈병 (Acute Lymphocytic Leukemia)

n n About 75% of all cases (60% in Korea) Peak incidence : 4 yr

Pathology n Subclasses according to morphologic, n immunologic, n genetic feature of leukemic blast n n n Definite diagnosis by bone marrow aspiration Chromosomal abnormalities n 80~90% in childhood ALL

Pathology n FAB class L 1: small lymphoblast predominant with little cytoplasm n L 2: larger & pleomorphic with increased cytoplasm. Irregular nuclear shape, predominant nucleoli n L 3: fine stippled and homogenous nuclear chromatin, predominant nuclei and deep blue cytoplasm with predominant nucleoli n

L 1 bone marrow

L 2 bone marrow

L 3 bone marrow

Clinical Manifestation n The first symptoms n n Pallor(anemia), bleeding(thrombocytopenia), and fever(neutropenia, malignancy) n n usually nonspecific (anorexia, irritability, and lethargy) prompt Dx About 50% n petechiae or mucous membrane bleeding

Clinical Manifestation n n Lymphadenopathy, splenomegaly, bone pain, arthralgia, … Rarely, signs of increased ICP ; headache and vomiting n n leukemic meningeal involvement T-cell ALL older and more often male n 66% have an anterior mediastinal mass n

n Diagnosis most have anemia n n thrombocytopenia n n by examination of bone marrow chest radiograph n n by the presence of blast cells on a PBS confirmed n n 25%에서 platelet counts > 100, 000/mm 3 suggested n n 25% 에서 Hb < 6 g/d. L mediastinal mass CSF examination for leukemic cells

Differential Diagnosis n Aplastic anemia and myelofibrosis, infectious mononucleosis infiltrate marrow a. b. c. d. Neuroblastoma Rhabdomyosarcoma Ewing sarcoma Rarely retinoblastoma

Treatment n Induction of remission n n Vincristine, prednisone, L-asparaginase with hydration, allopurinol, and sodium bicarbonate CNS prophylaxis RT(1800 Rad/2 wks) + IT MTX (6 times) n Good prognosis group – IT MTX n 최근 triple IT therapy n n MTX + Ara-C + hydrocortisone : weekly 6 times, then 2 months interval for 1 yr

Treatment n Maintenance of remission n n MTX, 6 -mercaptopurine (vincristine, prednisone) Immunotherapy Hematopoietic stem cell transplantation Supportive therapy Treatment about infection n Transfusion n Uric acid nephropathy 예방 n Oral hygiene n

Relapse n n The bone marrow is the most common site of relapse Extramedullary sites ; CNS and testes 1) CNS relapse ; increased ICP vomiting, headache, papilledema, and lethargy v 2) Tx : intrathecal chemotherapy and cranial irradiation Testes ; painless swelling of one or both testicles v Tx : irradiation of the gonads

Prognosis 예후 불량 요소 n a. b. c. d. e. f. g. h. i. j. k. l. Peripheral WBC count > 100, 000 /m. L 2 세 미만 or 10세 이상 Severe hepatomegaly or splenomegaly Male sex Leukemia cell ploidy 50 chromosome 또는 그 이하 Chromosomal translocation 의 존재 Platelet count < 100, 000 / mm 3, high Hb level Superior mediastinal mass FAB L 2 or L 3 B cell, T cell or pre-B cell Presence of CNS leukemia PAS 시약에 대한 blast cell 활성도의 감소

급성 골수구성 백혈병 (Acute Myeloid Leukemia)

Incidence n n n 15~20% of all childhood leukemias Neonatal or congenital leukemia 의 대부분 Trisomy 21, Fanconi anemia, Diamond. Blackfan anemia, Kostmann syndrome and Bloom syndrome에서 높은 incidence 를 보임. 또한 다른 악성 종양으로 치료받은 경우에서도 증가

Clinical Manifestation n n Signs and symptoms attributable to bone marrow failure initially with only anemia, leukopenia, or thrombocytopenia Bone pain is less common than in ALL Liver and spleen enlargement is common; lymphadenopathy Unexplained gingival hypertrophy or parotid gland swelling

Diagnosis n n The presence of at least 30% leukemic blast cell in the bone marrow Morphology and cytochemical analysis n n histochemical stain positive for myeloperoxidase, Sudan black, or nonspecific esterase FAB system

Diagnosis n Hemorrhagic diathesis (DIC at presentation or later) n n Translocation between chromosomes 8 and 21 (M 2) n n M 3 closely associated with chloroma Trisomy 8 and complete or partial deletion of chromosome 5 or 7

Diagnosis n Myelodysplastic syndrome n Resemblance to AML, but lower percentage of blast cells and characteristic features, including megaloblastosis

Diagnosis n Juvenile chronic myelogenous leukemia (JCML) n n n Unlike adult type CML, but may have features similar to those of AML, and myelodysplastic syndrome No philadelphia chromosome Nonspecific symptome : fever, malaise, liver and spleen enlargement, adenopathy Chronic despuamative maculopapular skin eruption Hb F ↑ (50%), leukocytosis 5세 이후에는 rare, type I neurofibromatosis에 호발

Treatment n Chemotherapeutic regimens : n n Retinoic acid as initial treatment for acute proyelocytic leukemia n n n anthracycline (daunorubicin, idarubicin) and cytarabine Reduce the risk of the hemorrhage, but is not curative Autologous or allogenetic bone marrow transplantation Intrathecal chemotherapy n Necessary to prevent CNS relapse

Prognosis n n Poor With aggressive therapy, 40~50% fo patients who achieve remission will survive (30~40% overall cure rate)

만성 골수성 백혈병 (Chronic Myeloid Leukemia)

n n n A clonal malignancy of the hematopoietic stem cell characterized by a specific translocation, the t(9; 22)(q 34; q 11) Philadelphia chromosome More common in adults and accounts for only 3 % of childhood leukemia Progression to a myeloid or lymphoid blast crisis

Pathology n n n Characterized by myeloid hyperplasia with increased numbers of differentiating myeloid cells in blood and bone marrow Philadelphia chromosome ; more than 95% Bcr-abl rearrangement (southern blot analysis or polymerase chain reaction technique)

Clinical Manifestation n Symptoms of hypermetabolism n n Weight loss, anorexia, and night sweats Symptoms of leukostasis n Visual disturbance or priapism, occur rarely

Diagnosis n Elevated white blood cell counts n n Elevated serum levels n n exceed 100, 000 /mm 3 with all forms of myeloid cells seen in the blood smear abnormally high platelet counts of vitamin B 12 and uric acid and reduced or absent leukocyte alkaline phosphatase activity Bone marrow n n Hypercelluar, with normal myeloid cells in all stages of differentiation. Megakaryocytes may be numerous Philadelphia chromosome

Treatment n Chemotherapy with busulfan (Myleran), or hydroxyurea 1. Chronic phase 1) 2) 3) 4) 2. Lymphoid blast crisis v 3. Busulfan Interferon alpha Glivecc (signal transduction inhibitor) Allogenic BMT Standard ALL treatment Myeloid crisis v Refractory to standard AML treatment

선천성 백혈병 n n Diagnosis within the first month of life Most cases are myeloid leukemia marked leukocytosis, petechiae, ecchymoses, and extramedullary involvement, massive hepatosplenomegaly, cutaneous nodule, and CNS leukemia n n n Occurs primarily in neonates with trisomy 21 or chromosome 21 mosaicism Poor prognosis Leukemic cell chromosome rearrangement affecting the q 23 region of chromosome 11