Patho - 4th Asessment - Chronic Leukemias - 27 Jan 2007

Chronic Leukemias

Chronic Leukemias AGENDA 

Chronic Myeloid Leukemia (CML)



Chronic Lymphocytic Leukemia (CLL)

CML Definition Epidemiology & Etiology Clinical Features Hematological Features Genetics

CML Definition •

Chronic Myeloproliferative Disorders (CMPDs) - CML - Polycythemia Vera (PV) - Essential Thrombocythemia (ET) - Chronic Idiopathic Myelofibrosis (CIMF)

CML Definition (cont’d) - Myeloproliferative disorder that originates in an abnormal pluripotent stem cell causing expanding pool of committed stem cells of granulocytic cell line. - Consistently associated with Philadelphia (Ph) chromosome. - Synonyms: Chronic Myelogenous Leukemia. Chronic Granulocytic Leukemia.

CML Epidemiology & Etiology - Most common CMPD. -

15-20% of all cases of leukemia. Incidence of 1: 100,000 population/year. Occurs at any age (Median age 5th – 6th decade) Unknown etiology (? Radiation Exposure)

CML Clinical Features - 20-40% of patients are asymptomatic at diagnosis. - Fatigue, weight loss, night sweating. - Splenomegaly +/- Hepatomegaly.

CML Hematological Features - Three phases: 1) Chronic Phase (CML-CP) 2) Accelerated Phase (CML-AP) 3) Blast Phase (CML-BP)

CML 

Hematological Features (cont’d) 1) Chronic Phase (CML-CP) CBC: - Leukocytosis (20-400 x 109/L) - Mild anemia - Thrombocytosis or normal platelets count - Basophilia +/- Eosinophilia

Peripheral Blood Smear (PBS) - Neutrophils in different stages (Neutrophils & Myelocytes) - Blast cells (< 2% of WBCs)

CML 

Hematological Features (cont’d) 1) Chronic Phase (CML-CP) Bone Marrow (BM) - Hypercellular (esp. megakaryocytes and myloid cells) - Similar findings to PBS - Blast cells < 5% of BM nucleated cells

CML 

Hematological Features (cont’d) 2) Accelerated Phase (CML-AP) CBC: - Increasing leukocytosis - Anemia - Thrombocytopenia - Basophilia (> 20% of WBCs)

PBS: - Blast cells 10-19% of WBCs

BM: - Blast cells 10-19% of BM nucleated cells - Dysplastic megakaryocytes & myeloid cells - marked fibrosis

CML 

Hematological Features (cont’d) 3) Blast (CML-BP) CBC: - Progressive anemia - Progressive thrombocytopenia - Progressive basophilia

PBS: - Blast cells > 20% of WBCs

BM: and

- Blast cells > 20% of BM nucleated cells - Blast lineage is myeloid in 70% of cases lymphoid in 30%.

Extramedullary blast proliferation:

CML Genetics - 99-100% of cases have Philadelphia (Ph) chromosome and/or the BCR/ABL fusion gene. - Ph chromosome = t(9;22). - Fusion of BCR gene on chromosome 22 with ABL gene on chromosome 9.

Chronic Leukemias AGENDA Chronic Myeloid Leukemia (CML) Chronic Lymphocytic Leukemia (CLL)

CLL Definition Epidemiology Clinical Features Hematological Features Genetics

CLL Definition - Neoplastic proliferation of mature lymphocytes involving peripheral blood and bone marrow. - One type of Chronic Lymphoproliferative Disorders (CLPD’s) - Distinguished from ALL by morphology and degree of maturation. - Chronic course. - B-CLL or T-CLL (rare)

CLL Epidemiology & Etiology - Comprises 90% of chronic leukemias. - Majority of patients are > 50 years old. - Male: Female ratio of 2:1 - Unknown etiology

CLL Clinical Features - Most patients are asymptomatic. -

Symptoms of anemia. Symptoms of thrombocytopenia Symptoms of leucopenia. Physical examination: Lymphadenopathy Hepatosplenomegaly

CLL Diagnosis CBC - Leukocytosis - +/- Anemia - +/- Thrombocytopenia

PBS - WBC: Mature Lymphocytes, Smear cells - RBCs: +/- spherocytosis

CLL Diagnosis (cont’d) BM - Evaluation of bone marrow aspirate and biopsy. - Infiltration by small mature lymphocytes.

CLL Diagnosis (cont’d) 

Immunophenotyping - >95% are B-CLL - B-CLL expresses: CD19, CD20, CD5, CD23, Light chain restriction (κ or λ)

- T-CLL expresses: CD3, CD8 or CD4, CD7, CD2, TCR αβ

CLL Genetics - 80% of B-CLL cases have abnormal karyotype. - Karyotypic abnormalities include: Trisomy 12 Deletions involving 13q Deletions involving 11q