Associate professor of Internal Medicine

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
Myelodysplastic Syndrome
LEUKEMIA.
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)
Chronic Lymphocytic Leukemia (CLL) DEFINITION CLL is a neoplastic disease characterized by proliferation and accumulation (blood, marrow and lymphoid.
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,
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)
Myeloprolifrative disorders -Chronic Myelogenouse Leukemia - Primary Poly Cythemia ( vira ) - Essential Thrombocythemia - Myelofibrose Myeloid Methaplasia.
C HRONIC LEUKEMIAS. Chronic myelogenous (granulocytic) leukemia Is characterized by an unregulated proliferation of myeloid elements in the bone marrow,
Chronic Leukemias. CMLCML CLLCLL CML A clonal disease results from an acquired genetic change in a pluri-potential hemopoietic stem cell within the BM.
INVESTIGATION OF LEUKOCYTES. CHANGES IN LETSKOTYC FORMULAS IN VARIOUS PATHOLOGICAL CONDITIONS. CLINICAL AND LABORATORY DIAGNOSIS OF HEMOBLASTOSIS.
Myelodysplastic Syndrome (MDS)
The myelodysplastic syndromes (MDS) Aquired Clonal disease of BM. comprise a heterogeneous group of malignant stem cell disorders characterized by : 1.
Chronic lymphocytic leukemia What is C.L.L. ? a chronic disease one particular type of lymphocyte (B-cells) accumulates. not rapidly growing and proliferating.
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.
..  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.
Hematopoetic Cancers. Hematopoesis Leukemia New diagnoses each year in the US: 40, 800 Adults 3,500 Children 21,840 died of leukemia in 2010.
Acute Leukemia Kristine Krafts, M.D..
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.
Acute lymphoblastic leukemia in children
CHAPTER 7 DISORDERS OF BLOOD CELLS & VESSELS. HEMATOPOIESIS Generation of blood cells Lymphoid progenitor cells = lymphocytes (WBCs) Myeloid progenitor.
Nada Mohamed Ahmed, MD, MT (ASCP)i. Objectives chronic myeloid leukaemia (CML) Haematopoietic malignancies Polycythemia vera (PV) Idiopathic myelofibrosis.
Anemia of Chronic Disease
Chronic myeloid leukaemia
PRIMARY THROMBOCYTHEMIA;-
Acute Leukemia Kristine Krafts, M.D..
Malignancies of hematopoietic cells. Leukemia
Myelodysplastic syndrome(MDS)
Differential WBC Counting
Acute myeloid leukemia
LEUKEMIAS H.A. MWAKYOMA, MD.
CLINICAL PROGRESSION INTRODUCTION METHOD CONCLUSION REFERENCES
CHRONIC LYMPHOCYTIC LEUKAEMIA CLL
Chronic Leukaemias Heterogeneous group of hematopoietic neoplasms
CHRONIC LEUKAEMIA Mousa Q.Hussein Assistant Professor
MLAB Hematology Keri Brophy-Martinez
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)
Chronic leukemias CML CLL MDS.
Associate professor of Internal Medicine
Case Study ….
Chronic Leukemia Kristine Krafts, M.D..
Hairy cell Leukemia Case study.
Myelodysplastic syndromes
A presentation By Abedelaziz Taha Hammash supervisor \ Mr
Dr. Hasan Fahmawi, MRCP(UK), FRCP(Edin)
Case study A 36-year-old woman presented with a two-month history of increasing fatigue and abdominal fullness with accompanying loss of appetite. There.
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:

Associate professor of Internal Medicine CHRONIC LEUKEMIA Dr. Hayam Hebah Associate professor of Internal Medicine AL Maarefa College

CHRONIC MYELOID LEUKEMIA

It is a myeloproliferative stem cell disorder resulting in proliferation of all hematopoietic lineages but manifesting predominantly by the granulocyte series Age 30-80 (peak at 55 y) , in all races Rare 1.8/100000 and accounts for 20% of all leukemias Cc is the chromosome abnormality called Philadelphia chromosome.

Philadelphia chromosome is a specific abnormality of chromosome 22, which is unusually short, acquired with CML. BCR-ABL1, that juxtaposes the ABL1 gene on chromosome 9 (region q34) to a part of the BCR("breakpoint cluster region") gene on chromosome 22 (region q11)  (Ph) chromosome is not sufficiently specific to diagnose CML (inspite presence in 90%) , since it is also found in (ALL, 25–30% in adult and 2–10% in pediatric cases) and occasionally in  (AML).

The disease has 3 phases: A chronic phase: responsive to ttt, last for 3-5 y( may reach 8 y after imatinib).mostly mature leukemia cells in blood and bone marrow. An accelerated phase( not always seen): disease control is more difficult. Immature WBCs(5-30%) in blood and BM. Clinically fever, weight loss and poor appetite . Median duration 6-9 mo. Blast crisis: disease transforms into acute leukemia either myeloid(70%) or lymphoblastic( 30%) which is relatively refractory to ttt. - Immature WBCs are in blood and bone marrow. Recurrent infections and anemia are typical. This is the cause of death in the majority of cases( median survival 3-6 mo).

C/P: lethargy, weight loss, sweating , abdominal discomfort , but 25% may be asymptomatic at diagnosis Splenomegaly in 90% and may be massive>15 cm below costal margin . Splenic friction rub may be heard in cases of splenic infarction. Hepatomegaly in 50% Lymphadenopathy : unusual - Gum hyperplasia

Investigations: N N anemia WBCs:10-600*10⁹/L (Typically, in excess of 100,000/mm3.) . In 1/3 of cases, platelets> 2000*10⁹/L Blood film: full range of granulocyte precursors from myeloblasts to mature neutrophils( predominantly neutrophils and myelocytes). Absolute increase in esinophils and basophils Nucleated red cells are common. At blast phase:↑circulating blasts, platelet count drop dramatically Bone marrow: confirm diagnosis, phase of disease, Philadelphia chromosome presence, RNA analysis for demonstration of BCR ABL gene product. LDH and uric acid may be high.

Tyrosine kinase inhibitors are the first line ttt of chronic CML and they reduce proliferation of WBCs

Chronic Lymphocytic Leukemia (chronic lymphoid leukemia, CLL)

BACKGROUND: CLL is a monoclonal disorder characterized by a progressive accumulation of functionally incompetent lymphocytes. B cells do not respond to antigens most common form of leukemia found in adults 30%. Allogeneic stem cell transplantation is the only known curative therapy.

The cells of origin in most patients with CLL are clonal B cells arrested in the B-cell differentiation pathway, intermediate between pre-B cells and mature B cells.  As in the case of most malignancies, the exact cause of CLL is uncertain. higher among whites than blacks. higher in males than in females 2:1 CLL is a disease that primarily affects the elderly, with the median age of presentation being 72 years. Prognosis: variable but most live 5-10 years.

C/P C/P: - discovered accidently in 70% -Onset is insidious, and can be discovered incidentally after a blood cell count is performed for another reason. Lymphadenopathy( painless) is the most common presenting symptom, but patients may present with a wide range of symptoms and signs. anemia, infections, weight loss, night sweats Early satiety and/or abdominal discomfort may be related to an enlarged spleen. Mucocutaneous bleeding and/or petechiae may be due to thrombocytopenia. Richter syndrome or Richter transformation refers to the transformation of CLL into an aggressive large B-cell lymphoma and is seen in approximately 3-10% of cases. Patients will often present with symptoms of weight loss, fevers, night sweats, muscle wasting, (ie, B symptoms) and increasing hepatosplenomegaly and lymphadenopathy. Treatment remains challenging and prognosis poor, with median survival in months.

Physical examination: In addition to localized or generalized lymphadenopathy, patients may manifest the following: Splenomegaly (30-54% of cases) Hepatomegaly (10-20% of cases) Petechiae Pallor

LN groups

Investigations Peripheral smear: CLL: Mature lymphocytosis( >5*10⁹/L) for longer than 3 months. The absolute neutrophil count is usually normal . RBCs and platelet counts are mildly decreased. Immunophenotyping: B cells express CD19 and CD23 with either kappa or lambda Ig light chains Characteristic aberrant T cell antigen CD5 ↑LDH and direct Coombs test( autoimmune hemolytic anemia) Serum immunoglobulins( hypogammaglobulinemia due to immune deficiency)

Bone marrow: not essential for diagnosis of CLL but may be helpful for prognosis and to monitor response to therapy. BM usually has more than 30% monoclonal lymphocytes and is either normocellular or hypercellular the peripheral smear or bone marrow should show normal mature small lymphocytes with less than 55% atypical or blast forms. Prognosis: Majority of stage A have normal life expectancy. Advanced CLL die from disease or infections. Rarely , CLL transform to an aggressive high grade lymphoma called Richter‘s transformation

Patients with fewer than 5000 B-lymphocytes/µL with lymphadenopathy and without cytopenias more likely have small lymphocytic lymphoma (SLL), although this diagnosis should be confirmed by lymph node biopsy. Large atypical cells, cleaved cells, and prolymphocytes are also often seen on the peripheral smear and may account for up to 55% of peripheral lymphocytes

Management: No specific treatment for most stage A. indications of treatment: Bone marrow failure Massive or progressive lymphadenopathy or splenomegaly Systemic symptoms as weight loss or night sweats. Rapidly increasing lymphocyte count Autoimmune hemolytic anemia or thrombocytopenia.

Treatment & Management CLL patients do not need to be treated with chemotherapy until they become symptomatic or display evidence of rapid progression of disease, as characterized by the following: Weight loss of more than 10% over 6 months Extreme fatigue Fever related to leukemia for longer than 2 weeks Night sweats for longer than 1 month Progressive marrow failure (anemia or thrombocytopenia) Autoimmune anemia or thrombocytopenia not responding to glucocorticoids Progressive or symptomatic splenomegaly Massive or symptomatic lymphadenopathy Progressive lymphocytosis, as defined by an increase of > 50% in 2 months or a doubling time of less than 6 months

Stages B&C Oral chemotherapy with chlorambucil. Recently fludarabine, cyclophosphamide,rituximab In BM failure or cytopenias---steroids Supportive care: Transfusions, ttt of infections, immunoglobulin replacement. Radiotherapy splenectomy

Prolymphocytic leukemia In males >60 y 25% of cases are T cell variety Massive splenomegaly Leucocytic count exceeds( 400*10⁹/L) Cc cell is a large lymphocyte with a prominent nucleolus. Prognosis ---very poor Ttt------unsuccesful

Hairy cell leukemia Rare B cell lymphoproliferative disorder Male to female 6:1 Median age 50 y c/p: ill health ,infections, splenomegaly Cc severe neutropenia , monocytopenia, hairy cells in the blood and bone marrow Express CD25 and CD 103

MYELODYSPLASTIC SYNDROME MDS presents with consequences of BM failure in old age( median 69 y) Blood film: cytopenias and abnormal dysplastic cells(macrocytic RBCs, hypogranular neutrophils with nuclear hyper or hyposegmentation. Bone marrow: hypercellular with dysplastic changes in the 3 cell lines. ↑blast cells but <20% Chromosomes 5 or 7 abnormalities. DISEASE IS INCURABLE Supportive ttt is the mainstay ttt Progress to AML

Myelodysplasia: The myelodysplastic syndromes are all disorders of the hematopoietic stem cells in the bone marrow (only related to myeloid lineage). In MDS, hematopoiesis (i.e., blood production) is disorderly and ineffective FAB classification: Refractory anemia (RA) Refractory anemia with ring sideroblasts (RARS) Refractory anemia with excess blasts (RAEB) Refractory anemia with excess blasts in transformation (RAEB-T) Chronic myelomonocytic leukemia (CMML), not to be confused with chronic myelogenous leukemiaor CML

Thank you