C HRONIC LEUKEMIAS. Chronic myelogenous (granulocytic) leukemia Is characterized by an unregulated proliferation of myeloid elements in the bone marrow,

Slides:



Advertisements
Similar presentations
TA OGUNLESI (FWACP)1 CHILDHOOD LEUKAEMIA. TA OGUNLESI (FWACP)2 LEUKAEMIA Heterogenous group of malignant disorders Characterised by uncontrolled clonal.
Advertisements

Introduction To Haematological Malignancies
1 Leukemia. 2 Leukemia A group of malignant disorders affecting the blood and blood-forming tissues of A group of malignant disorders affecting the blood.
LEUKEMIA.
Armaan Khalid. What is Leukaemia?  Cancer of the blood or bone marrow  Can be classified: Acute/chronic Myeloid/lymphoid.
Chronic leukaemias Chronic myelogenous leukaemia Chronic myelogenous leukaemia Chronic lymphocytic leukaemia Chronic lymphocytic leukaemia.
LEUKEMIA—HEMATOLOGY {S1}
1 Chronic Leukemia Dr.Huad alkarim.. 2 What Are the Types of Chronic Leukemia?
This lecture was conducted during the Nephrology Unit Grand Ground by Nephrology Registrar under Nephrology Division, Department of Medicine in King Saud.
WHO CLASSIFICATION OF MYELOID NEOPLASMS 2000  Chronic myeloproliferative disorders (CMPD)  Myelodysplastic / myeloproliferative diseases (MDS/MPD) 
Chronic lymphocytic leukemia (1)
Chapter 17 Chronic Leukemias.
Chronic Lymphocytic Leukemia. Definition Clonal B cell malignancy. Progressive accumulation of long lived mature lymphocytes. Increase in anti-apoptotic.
Chronic Leukemia Dr. Rania Alhady Chronic Lymphocytic leukemia (CLL):
Chronic leukemias. Chronic myelogenous (granulocytic) leukemia Is characterized by an unregulated proliferation of myeloid elements in the bone marrow,
CHRONIC MYELOID LEUKAEMIA Dr Rosline Hassan Department of Haematology School of Medical Sciences Universiti Sains Malaysia.
Chapter 25: Acute Lymphoblastic Leukemia. Causes a wide spectrum of syndromes – From involvement of bone marrow and peripheral blood(leukemias) to those.
Acute Myeloid Leukemias (AML)
O THER MALIGNANT LYMPHOPROLIFERATIVE DISORDERS The lymphomas and plasma cell problems.
Myeloprolifrative disorders -Chronic Myelogenouse Leukemia - Primary Poly Cythemia ( vira ) - Essential Thrombocythemia - Myelofibrose Myeloid Methaplasia.
Blood Pathologies. Infectious Mononucleosis EBV (highly contagious, hence “kissing disease”) specifically attacks B lymphocytes  massive T lymphocyte.
Chronic Leukemias. CMLCML CLLCLL CML A clonal disease results from an acquired genetic change in a pluri-potential hemopoietic stem cell within the BM.
Case Study MICR Hematology Spring, 2011 Case # 5 Hee Jin Kim, Hooman Nikizad and Arthur Omuro.
INVESTIGATION OF LEUKOCYTES. CHANGES IN LETSKOTYC FORMULAS IN VARIOUS PATHOLOGICAL CONDITIONS. CLINICAL AND LABORATORY DIAGNOSIS OF HEMOBLASTOSIS.
Myeloproliferative Disorders (MPDs)
Leukaemias and lymphomas. Etiology, pathogenesis. Diagnostics
Leukemia By: Gabie Gomez. What is Leukemia? Blood consists of plasma and three types of cells, each type has a special function. RBC, WBC and Platelets.
4th Year Medical Student KAU
Hematology and Hematologic Malignancies
Chronic leukemia 1. Chronic Lymphocytic leukemia (CLL) * Definition: Chronic neoplastic disorder characterized by accumulation of small mature-looking.
Chronic myeloid leukaemia (CML)
Chronic myeloid leukaemia( CML);. CML is an excessive proliferation with fairly normal maturation. The disease occurs mainly between 30 and 80 years with.
CHRONIC LEUKEMIA Dr. Hayam Hebah Associate professor of Internal Medicine AL Maarefa College.
Heterogeneous group of hematopoietic neoplasms Uncontrolled proliferation and decreased apoptotic activity with variable degrees of differentiation Composed.
8/12/20091 Leukemia. 2 Leukemia A group of malignant disorders affecting the blood and blood-forming tissues of A group of malignant disorders affecting.
..  Neoplastic proliferation of small mature appearing  lymphocytes and account 25% of leukemia  It is rare before 40 years of age, the median age.
MLAB 1415: Hematology Keri Brophy-Martinez
MLAB Hematology Keri Brophy-Martinez
White blood cells and their disorders Dr K Hampton Haematologist Royal Hallamshire Hospital.
Acute Leukemia Kristine Krafts, M.D..
By: Ashlynn Hill. Patrice Thompson  3 year who is battling leukemia.  The doctors suggest a bone marrow transplants for a long term survival.  Neither.
Myeloproliferative disorder Clonal evolution Clonal evolution & stepwise progression to fibrosis, marrow failure or acute blast phase.
Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Chapter 28 Disorders of White Blood Cells and Lymphoid Tissues.
Chronic leukemias أ. م. د. محمد شنين علي العبادي معاون عميد كلية الطب / جامعة كربلاء ورئيس فرع الامراض والطب العدلي M. B. Ch. B. & F. I. C. P.(Hematopathology)
LEUKEMIA Dr. Omar Alshaer. Acute Leukemia.
AML Clinical Presentation. Clinical Presentation: Symptoms Fatigue (50%) Anorexia and weight loss Fever with or without an identifiable infection (10%)
Nada Mohamed Ahmed, MD, MT (ASCP)i. Objectives chronic myeloid leukaemia (CML) Haematopoietic malignancies Polycythemia vera (PV) Idiopathic myelofibrosis.
Associate professor of Internal Medicine
Acute Leukemia Kristine Krafts, M.D..
Blood Biochemistry BCH 577
Malignancies of hematopoietic cells. Leukemia
Leukemia DR Ahmed Gamal Consultant Adult hematology and SCT , KKUH
LEUKEMIAS H.A. MWAKYOMA, MD.
CHRONIC LYMPHOCYTIC LEUKAEMIA CLL
Chronic Leukaemias Heterogeneous group of hematopoietic neoplasms
11 th lecture Chronic myeloid leukaemia By DR Fatehia Awny Faculty of Health Science Beirut Arab University
Chronic Leukaemias Heterogeneous group of hematopoietic neoplasms
CHRONIC MYELOID LEUKEMIA (CML)
Associate professor of Internal Medicine
Case Study ….
Chronic Leukemia Kristine Krafts, M.D..
Acute leukemia.
Diagnostic Hematology
Hairy cell Leukemia Case study.
A presentation By Abedelaziz Taha Hammash supervisor \ Mr
Neoplastic disorder.
Chronic Leukemia Dr. Noha Noufal.
CHRONIC LEUKEMIA BY: DR. FATMA AL-QAHTANI CONSULTANT HAEMATOLOGIST
MYELOID LEUKEMIAS Dr. B.V.Vydehi M.D PROFESSOR OF PATHOLOGY
Presentation transcript:

C HRONIC LEUKEMIAS

Chronic myelogenous (granulocytic) leukemia Is characterized by an unregulated proliferation of myeloid elements in the bone marrow, liver and spleen, leading to marked leukocytosis and organomegaly. Incidence 20% of all leukemias Primarily affects adults years old, with a peak incidence at Etiology, pathogenesis and physiology May occur after anything that can induce chromosomal aberrations such as ionizing radiation, alkylating agents, and exposure to other biologically active chemicals

C HRONIC LEUKEMIAS Appears to be a clonal hematopoietic stem cell disorder 90% of CML have a Philadelphia (Ph’) chromosome (reciprocal translocation between chromosome 22 and chromosome 9 by cytogenetic karyotype studies. A BCR/ABL hybrid gene is created when the breakpoint is in the major breakpoint cluster region of chromosome 22. The gene product (p290) has enhanced tyrosine kinase activity that results in Increased granulocyte-colony stimulating factor Increased platlet derived growth factor Suppression of apoptosis in hematopoietic cells The remaining 5-10% are positive for the translocation using more sensitive DNA studies such as RT-PCR or fluorescent in situ hybridization The Ph’ chromosome is found in all hematopoietic cells except T lymphocytes (and sometimes B lymphocytes) The Ph’ cells have a growth advantage over normal cells

P HILADELPHIA C HROMOSOME IN CML

P HILADELPHIA CHROMOSOME

C HRONIC LEUKEMIAS The progeny of the original malignant cell, after 2-6 years, eventually replace the normal hematopoietic elements and become the prominent cell By the time the disease becomes clinically evident, nearly all the myeloid cells in the bone marrow are Ph’ + As the disease progresses, the Ph’ + cells undergo additional chromosomal aberrations and the patients ultimately terminate in a blast crisis. Note - A Philadelphia chromosome generated by a break in the minor breakpoint region of chromosome 22 resulting in a fusion protein product, p190, may be seen in AML. The clinical course of the disease occurs in three stages Asymptomatic, proliferative stage – Ph’+ cells appear in the bone marrow and the peripheral leukocyte count is normal

C HRONIC LEUKEMIAS The symptomatic, chronic stage occurs after about 6.3 years – at this stage the peripheral leukocyte count is increased and immature granulocytes appear in the peripheral blood. The hyperproliferation is easily controlled with chemotherapy, but the remission is only temporary and patients still have Ph’+ cells in the bone marrow. Accelerated or acute stage – this is also called a blast crisis (>30% blasts in the bone marrow) Cellular proliferation is uncontrollable and resembles AML. The medium survival is 10 weeks Signs and symptoms Malaise Fatigue due to anemia Fever

C HRONIC LEUKEMIAS Weight loss Sweating Bone aches and fullness in upper abdomen due to expansion of the bone marrow and organomegaly Bleeding, petechiae, ecchymoses from abnormal platlets Lab features Leukocytosis and anemia; ¾ have WBC counts> 100 x 10 9 /L Normal appearing granulocytes at all stages of maturation are seen in the peripheral smear (they are not functionally normal, however); < 10% are blasts and promyelocytes Many have a thrombocytosis with variation in shape; platlet function is frequently abnormal Low to absent leukocyte alkaline phosphatase activity (Low LAP score)

CML

CML – ABNORMAL PLATLET

CML – BLAST TRANSFORMATION

C HRONIC LEUKEMIAS Treatment Median survival from the time of diagnosis used to be ~ 3 years The prognosis is better if the WBC count is lower and the % of blasts is low Chemotherapy with a single agent has been used and ~ 75% in the chronic phase of the disease go into remission. However, Ph’+ cells remain in the bone marrow Bone marrow transplants during the chronic phase (high dose chemo/radiotherapy followed by infusion of normal, compatible bone marrow) used to be the best therapy A new drug, Gleevec, is now available and it specifically targets the BCR/ABL gene product. The Ph’ + cells are destroyed, while normal cells are unaffected

C HRONIC LEUKEMIAS Eosinophilic leukemia Is this a distinct entity or a variant of CML? 30-70% eosinophils with a WBC count > 30 x 10 9 /L and a shift to the left The prognosis is poor with a median survival of < 1 year Basophilic leukemia Is this a distinct entity or a variant of CML? Is extremely rare with 40-80% basophils and a left shift

C HRONIC LEUKEMIAS Chronic lymphocytic leukemia This is predominantly a disease of the elderly; > 90% are over 50 and 2/3 are over 60; male:female is 2:1 Is characterized by peripheral and bone marrow lymphocytosis and a survival of a few years to > 10 years This is a B cell abnormality The lymphocytes appear normal, but are immunologically incompetent. However, some functionally normal B cells remain and there is a normal T cell pool

C HRONIC LEUKEMIAS Etiology Genetic factors are important since it runs in families Clinical course The pace of the disease varies and is dependent on the rate of accumulation of abnormal lymphocytes Median survival is 3-4 years, but 10-15% survive > 10years There is no tendency for blast transformation, but complications of advanced disease result from progressive accumulation of long-lived, poorly functional lymphocytes. Signs and symptoms Organomegaly and lymphadenopathy Often discovered accidentally Fatigue

C HRONIC LEUKEMIAS Near the end – bruising, pallor, fever, and weight loss Lab features Absolute lymphocytosis of x 10 9 /L Lymphocytes usually appear normal, but they are markedly fragile and smudge cells are seen on the peripheral smear It is not necessary to do a bone marrow biopsy for diagnosis. Anemia occurs late in the disease and may be due to decreased production secondary to marrow infiltration, hypersplenism, or autoimmune hemolytic anemia: the same things may cause neutropenia or thrombocytopenia Hypogammaglobulinemia as the disease progresses

CLL WITH SMUDGE CELLS Smudge cell

C HRONIC LEUKEMIAS Prognosis is related to the extent and distribution of the disease – also called the stage: Stage A – lymphocytosis without anemia or thrombocytopenia and < 3 areas of lymphoid involvement (lymph nodes, spleen, liver) Stage B – same as A, but > 3 areas of lymphoid involvement Stage C – lymphocytosis with anemia, thrombocytopenia, or both

C HRONIC LEUKEMIAS Treatment Stage A – observe only Stage B with no symptoms – same as A Stage B with symptoms - therapeutic intervention to relieve signs and symptoms Stage C - therapeutic intervention to relieve signs and symptoms The goal of therapy is simply to relieve signs and symptoms A new monoclonal antibody, CAMPATH, that targets the mature B cells in B cell CLL is now being used.

C HRONIC LEUKEMIAS Differential diagnosis Must distinguish between CLL and prolymphocytic leukemia, hairy cell leukemia, large, granular lymphocyte leukemia, Sezary’s syndrome, and circulating lymphoma cells Prolymphocyte leukemia This is an aggressive leukemic disorder of mature B or T cells > 55% of the lymphocytes are prolymphocytes which are large with moderate amounts of pale basophilic cytoplasm, mature condensed chromatin, and a single prominent nucleolus

P ROLYMPHOCYTIC LEUKEMIA

C HRONIC LEUKEMIAS Hairy cell leukemia This is mainly a disease of elderly men Patients present with marked splenomegaly, but not lymphadenopathy Patients have fatigue and malaise Pancytopenia The peripheral smear shows atypical mononuclear lymphocytoid cells with hairy projections on their surfaces The bone marrow yields a dry tap because the malignant cells are often surrounded by fibrosis Splenectomy and interferon as well as new chemotherapeutic drugs are successful in promoting long lasting remissions

H AIRY CELL LEUKEMIA

C HRONIC LEUKEMIAS Large, granular lymphocyte leukemia T cell or NK cell in origin Is characterized by a moderate lymphocytosis composed of cells with abundant pale-staining cytoplasm and nuclei with mature, clumped chromatin Anemia is common, but neutropenia is rare Most patients survive > 10 years Sezary’s syndrome Occurs in patients with cutaneous T cell lymphoma The lymphocytes seen in the peripheral smear have a very large, convoluted nuclear outline and finely distributed chromatin

L ARGE, GRANULAR LYMPHOCYTE LEUKEMIA

SEZARY’S SYNDROME

C HRONIC LEUKEMIAS Circulating lymphoma cells Patients with non-Hodgkins lymphoma may develop peripheral blood involvement