Presentation on theme: "LEUKEMIAS By Dr Aamer Aleem Consultant Hematologist"— Presentation transcript:
1LEUKEMIAS By Dr Aamer Aleem Consultant Hematologist Associate Prof. of MedicineCollege of Medicine & KKUHRiyadh, Saudi Arabia
2LeukemiasLeukemias are a group of cancers of the blood or bone marrow and are characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes).Leukemia is a broad term covering a spectrum of diseases. Any of various acute or chronic neoplastic diseases of the bone marrow in which unrestrained proliferation of white blood cells occurs and which is usually accompanied by anemia and thrombocytopenia
3Classification of leukemias Two major types (4 subtypes) of leukemiasAcute leukemiasAcute lymphoblastic leukemia (ALL)Acute myelogenous leukemia (AML)(also "myeloid" or "nonlymphocytic")Chronic leukemiasChronic lymphocytic leukemia (CLL)Chronic myeloid leukemia (CML)(Within these main categories, there are typically several subcategories)
4Myeloid vs Lymphoid Any disease that arises from the myeloid elements (white cell, red cell, platelets) is a myeloid disease….. AML, CMLAny disease that arises from the lymphoidelements is a lymphoid disease….. ALL, CLL
5Acute vs. chronic leukemia Acute leukemias:Young, immature, blast cells in the bone marrow(and often blood)More fulminant presentationMore aggressive course• Chronic leukemias:Accumulation of mature, differentiated cellsOften subclinical or incidental presentationIn general, more indolent (slow) courseFrequently splenomegalyMature appearing cells in the B. marrow and blood
6Acute vs. chronic leukemia Leukemias are classified according to cell of origin:Lymphoid cellsALL - lymphoblastsCLL – mature appearing lymphocytesMyeloid cellsAML – myeloblastsCML – mature appearing neutrophilsOn a CBC, if you see:Predominance of blasts in bloodconsider an acute leukemiaLeukocytosis with mature lymphocytosisconsider CLLLeukocytosis with mature neutrophiliaconsider CML
7Acute leukemiasDefinition: Malignancies of immature hematopeotic cells.(> 20% blast cells in the bone marrow)Types: Acute Myeloid Leukaemia (AML)Acute Lymphoblastic leukemia (ALL)Groups: Childhood (< 15) > 80% ALLAdult (> 15) > 80% AMLElderly (> 60 years)
13Laboratory Tests CBC a. Anemia b. Trombocytopenia c. WBC High Normal LowCoagulation Studies (M3-DIC)Biochemical Studies (U/E, LFT)Cont..
14Peripheral Blood smear – blasts in almost all cases Bone Marrow Examination (>20% blasts)Flow cyometry(Surface immunophenotype of blast cells)Cytogenetics (chromosomal analysis)CSF analysis (all ALL patients, some AML)HLA typing (for younger high risk patients)
15Diagnostic methods of importance Bone marrow aspirate & Romanowsky stain (morphology) Enumeration of blasts, maturing cells, recognition of dysplasiaCytochemistry Myeloperoxidase, Sudan Black B, esterases to determine involved lineagesImmunophenotyping Defines blast cell lineage commitment as myeloid, lymphoid or biphenotypicCytogenetics & molecular studies (FISH, PCR) Detects clonal chromosomal abnormalities, including those of prognostic importance
21Discover the latest technology from Bayer <> BloodlineHome AboutEducational FeaturesImage Atlas Case Studies Private Lectures Conference Reviews Journal Articles Book Reviews GlossaryResourcesConference Calendar Grants & Fellowships Hematology Links Full Text Journals ClassifiedsSpecialtiesBMT/Stem Cell Cord Blood Thrombosis Hemostasis Laboratory Malignancies Pediatrics Red Cell Disorders Transfusion Medicine VeterinaryNewsHematology News BloodLink Newsletter Blood News UpdateDiscussionToday's Discussion Create New Topic List by TopicPlasma Cells, Acute myelomonocytic (M-4) leukemiaClump of Plasma Cells most of which are small with a deep basophilic blue cytoplasm. Two cells in the center are partially smudged and show a paler cytoplasm and less dense and redder staining nuclear chromatin. Acute myelomonocytic (M-4) leukemia. Marrow - 100XImage ID: Copyright Carden Jennings Publishing Co., Ltd. All rights reserved. The material available at this site is for educational purposes only and is NOT intended for any diagnostic, clinically related, or other purpose. Carden Jennings Publishing Co., Ltd., assumes no responsibility for any use or misuse of this material and makes no warranty or representation of any kind with respect to the material available at this site.Clump of Plasma Cells most of which are small with a deep basophilic blue cytoplasm. Two cells in the center are partially smudged and show a paler cytoplasm and less dense and redder staining nuclear chromatin. Acute myelomonocytic (M-4) leukemia. Marrow - 100X
22Four Immature Monocytes Four Immature Monocytes. Two of the cells are shedding large Cytoplasmic Fragments which can resemble a Megathrombocyte and/or Platelets. Acute Monocytic Leukemia (M-5). Blood - 100X
23Cytoplasmic Fragments from Leukemic Monocytes that resemble Platelets Cytoplasmic Fragments from Leukemic Monocytes that resemble Platelets. Two fragments (top right and lower left) are probably valid platelets. Seven immature monocytes. Acute Monocytic Leukemia (M-5). Blood -100X
24Acute Myeloid Leukaemia (AML) Prognostic factors in AML Age Above the age of 50 years the complete remission rate falls progressivelyCytogenetics Three risk groups definedGood risk: patients with t(8;21), t(15;17) and inv/t(16)Intermediate risk: Normal, +8, +21, +22, 7q-, 9q-, abnormal 11q23, all otherPoor risk: patients with -7, -5, 5q-, abnormal 3q and complex karyotypesWheatley K, Burnett AK, Goldstone AH et al. Br J Haem 1999; 107: 69-79Grimwade D, Walker H, Oliver F et al. Blood 1998; 92:
25Acute Myeloid Leukaemia (AML) Prognostic factors in AML Treatment responsePatients with >20% blasts in the marrow after first course of treatment have short remissions (if achieved) and poor overall survivalSecondary AMLPatients with AML following chemotherapy or myelodysplasia respond poorlyTrilineage myelodysplasiaPatients with trilineage myelodysplasia have a lower remission rateWheatley K, Burnett AK, Goldstone AH et al. Br J Haem 1999; 107: 69-79Grimwade D, Walker H, Oliver F et al. Blood 1998; 92:
26Acute Myeloid Leukaemia (AML) Treatment and prognosis of AML Intensive chemotherapyPatients < 55 years old: 80% remissionsPatients > 55 years old: progressive reduction in remission rateBone marrow (stem cell) transplantationAutologous and allogeneic transplants reduce the relapse rateImportance of cytogenetics for prognosis in children and adults < 55 years oldGood risk cytogenetic group91% remissions, 65% five year survivalWheatley K, Burnett AK, Goldstone AH et al. Br J Haem 1999;107: 69-79Grimwade D, Walker H, Oliver F et al. Blood 1998; 92:
27Acute Lymphoblastic Leukaemia (ALL) Prognostic factors in ALLPoor Prognostic FactorsAge < 2 yrs and > 10 yrsMale sexHigh WBC count ( > 50 х109/L)Presence of CNS diseaseCytogenetics Good risk Poor riskHyperdiploid (>50 ch) Hypodiploid,t(9:22), t(4:11)Bone Marrow: Blasts present on day 14Day 28:No complete response
30Treatment of acute leukemias Specific therapy (chemotherapy)Supportive treatmentStages of TherapyInductionConsolidationMaintenance
31(Treatment of acute leukemias) InductionObtained by using high doses of chemotherapySevere bone marrow hypoplasiaAllowing regrowth of normal residual stem cells to regrow faster than leukemic cells.RemissionNormal neutrophil countNormal platelet countNormal hemoglobin levelRemission defined as < 5% blast in the bone marrow
32(Treatment of acute leukemias) ConsolidationDifferent or same drugs to those used during inductionHigher doses of chemotherapyAdvantage: Delays relapse and improved survival
33(Treatment of acute leukemias) MaintenanceSmaller doses for longer periodProduce low neutrophil counts & platelet countsObjective is to eradicate progressively any remaining leukemic cells.
34(Treatment of acute leukemias) Supportive CareVascular access (Central line)Prevention of vomitingBlood products (Anemia, ↓Plat)Prevention & treatment of infections(antibiotics)Management of metabolic complications
35ALL vs AML ALL Induction Consolidation Maintenance CNS prophylaxis all patientsAMLInductionConsolidationNo maintenanceCNS – Selected group only
37CHRONIC LYMPHOCYTIC LEUKAEMIA (CLL) Neoplastic proliferations of maturelymphocytes.Distinguished from ALL byMorphology of cells.Degree of maturation of cells.Immunologically immature blasts in ALL.CLL affects mainly elderly.
38SYMPTOMS of CLL May be entirely absent in 40% Weakness, easy fatigue, vague senseof being illNight sweatsFeeling of lumpsInfections esp pneumonia
39PHYSICAL EXAMINAITON-CLL PallorLymphoadenopathya Cervical, supraclavicular nodes more commonly involved than axillary or inguino-femoralb Non-tender, not painful, discrete, firm, easily movable on palpationSplenomegely, mild to moderateHepatomegaly
41LABORATORY TESTS-CLL CBC Lymphocyte count > 5 x 109/L Platelets may be decreasedHb may be lowBlood filmPB immunophenotypingBone marrow biopsy (needed before starting treatment)Imaging
42TREATMENT OF CLL Observation Chemotherapy. Oral chlorambucil Fludarabine, cycloImmunotherapy Anti-CD 20 (rituximab),Anti-CD 52 (Alemtuzumab)FC-R is the current standardIndications for starting chemotherapyProgressive SymptomsProgressive Anemia or ThrombocytopeniaBulky LN, large spleenRecurrent Infections
43CHRONIC MYELOID LEUKEMIA CML is a clonal stem cell disorder characterised by increased proliferation of myeloid elements at all stages of differentiation.Incidence increases with age, M > F.
44CML is characterised by 3 distinct phases Chronic Phase:Proliferation of myeloid cells, which show a full range of maturation.Accelerated Phase decrease in myeloid differentiation occurs.Blast crisis (acute leukemia)
45CLINICAL PRESENTAITON OF CML SymptomsAsymptomatic (50% of patients)FatigueWeight lossAbdominal fullness and anorexiaAbdominal pain, esp splenic areaIncreased sweatingEasy bruising or bleeding
46SIGNS OF CML Splenomegaly (95%) (50% of patients have a palpable spleen ≥ 10 cm BCM, Usually firm and non-tender)Hepatomegaly (50%)Sternal tenderness is a reliable sign of disease. Is usually limited to a small area, most commonly the midbody.(fifth intercostal disease).
47DIAGNOSIS OF CML Chronic phase. Peripheral blood – neutrophil leukocytes 20, >500, 000/ L basphilia LAP scoreblasts < 5%Nucleated RBCsThrombocytosisAnaemia
48CYTOGENETICS OF CML Reciprocal translocation of Philadelphia (Ph) chromosome is an acquired cytogenetic abnormality in all leukaemia cells in CMLReciprocal translocation ofchromosomal material betweenchromosome 22 and chromosome 9.t(9;22)
57TREATMENT OF CMLTyrosine kinase inhibitor (TKI) Imatinib (Glivec) is the first line treatmentIn resistent cases 2nd line TKIs (Nilotinib, Dasatinib, Bosutinib) very usefulAllogenic bone marrow trasnsplantation can be curative in pts resisrant to TKIs but has significant complications & mortalityAccelerated and blast phaseGlivec, 2nd line TKIsTreat like AML or ALL followed by BMT
58CML VS LEUKEMOID REACTION LA P ScorePhiladelphia ChromosomeBasophiliaSplenomegaly
59transplantation in leukemias Bone marrow or PBSCtransplantation in leukemiasTypes of transplantAutologous transplantAllogeneic TransplantPurpose of transplantAutologous-To deliver a high dose of chemo to kill any residual cancer(lymphoma, multiple myeloma)Allogeneic-To eradicate residual leukemia cells-Graft vs leukemia effect
60transplantation in leukemias Bone marrow or PBSCtransplantation in leukemiasTechnique of transplantationMHC + HLA matchingChemotherapyTotal body irradiationGVHD prophylaxisComplications of transplantationProlonged BM suppression (graft failure)Serious infectionsMucositisGraft versus host disease (GVHD)