3 Acute Leukemias Blast predominate Child or elder Short & drastic courseALL – Lymphoblasts (pre-B or pre-T)AML – Myeloblasts
4 Chronic Leukemias More mature cells Middle age Longer & less devastating courseCLL – LymphocytesCML – Myeloid stem cells
5 Acute Leukemiasaccumulation of blasts in the marrow
6 Acute Lymphoblastic Leukemia (ALL) ChildrenLymphoblasts (pre-B or pre-T)Neoplastic transformation of thelymphoid stem cells• Progressive accumulation of Lymphoblasts in the bone marrow• Suppression of normal hemopoiesis
8 • Primarily a disease of children and young adults • B-cell subtype (80%)• T-cell subtype (20%)
9 ALL Abrupt onset Signs and symptoms related to: • Suppression of normal hemopoiesisbone pain and tenderness• Tissue infiltration ( megaly)(lymph nodes, spleen, liver, testicles, CNS)• Mediastinal mass ( T-ALL ) thymus involvementHeadache, vomiting, nerve palsies from meningeal spread.
11 ALL - PROGNOSIS Favorable: Unfavorable: Pre-B T or mature B Age < 1, > 10WBC < /uL > /uLFemale MaleMinimal organ Prominent organinvolvement involvement
12 ALL Prognosis: • Age 3-7, pre-B, > 90% - CR ( 2/3 - cure ) • Adults, mature B and T-ALL:Less favorableTherapy: Chemotherapysupportive care, BMT
13 ACUTE MYELOGENOUS LEUKEMIA ( AML ) AdultsMyeloblastsmonoblasts, eosinoblasts, megakarioblasts, proerythroblasts, basophiloblastsAuer rods in the cytoplasm of the cellsVery rapidly progressive malignancy
16 Differentiation from ALL may be made by microscopy – presence of Auer Rods. Can also be made based on immunotyping and molecular methods.Clinical features based onMarrow failure –anemia, bleeding, DIC, infection…Leukemic infiltration – bone pain, CNS signs, hepatosplenomegaly, lymphadenopathy…Constitutional upset -- malaise, fever, weakness, polyarthritis.
17 Course:• Rapidly fatal if untreated (< 2 mo )• Median survival - 3 years after chem..• Adverse prognostic factors:Age > 60Previous chemotherapyLeukocytosis > 100,000 /ulTherapy: Chemotherapy, supportive, BMT
18 ***Remember this*** For Acute leukemias acute leukemias = too many blasts in the marrow2 broad categories: AML vs. ALLa hematologic urgencyprognosis is poor in adults; but good in kids with ALL.
19 CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) A monoclonal lymphoproliferativedisorder characterized by lymphocytosis(>4000/cu.mm),lymphadenopathy and splenomegalyB - CLL > 95%T - CLL
20 CLL • Most common adult leukemia in Western society (30% of all leukemias)• Monoclonal proliferation of the small lymphocytes…• Age > 40 M:F / 2:1
29 **Philadelphia chromosome** Hybrid chromosome with translocation between the long arm of chr. 9 and long arm of chr t(9:22).May be present in granulocyte, RBC or platelet precursors in more than 95% of CML..Absence of these chr. may have worse prognosis.
30 CML - Clinical Features % of all leukemias; age 25-60Symptoms:- non-specific- related to hypermetabolism (high cell turnover)- related to splenomegalyCourse:- chronic phase (mean survival, 3-4y)- accelerated phase- blast crisis / myeloid or lymphoid (survival, < 1y)Therapy: chemotherapy; BMT
31 CML: Sustained granulocytosis with immature cells; low LAP score; bone marrow pathology; Philadelphia chromosomeLAP – leukocyte alkaline phosphatase