Leukemia

LEUKEMIA Neoplastic proliferation of WBC in the blood and bone marrow. Acute leukemia - Blast cells - Rapidly fatal if not treated Chronic Leukemia - More mature Cells - Longer life expectancy CAUSES AND RISK FACTORS Smoking is a considerable risk factor for leukemia, especially a type of leukemia called acute myelogenous leukemia, or AML. The carcinogens in cigarettes are absorbed by the lungs and then travel to the bloodstream. It is estimated that 1 in 4 cases of AML are caused by smoking. Very high levels of radiation — People exposed to very high levels of radiation are much more likely than others to develop leukemia. Very high levels of radiation have been caused by atomic bomb explosions (such as those in Japan during World War II) and nuclear power plant accidents (such as the Chernobyl accident in 1986 Working with certain chemicals — Exposure to high levels of benzene in the workplace can cause leukemia. Benzene is used widely in the chemical industry. Chemotherapy — Cancer patients treated with certain cancer-fighting drugs sometimes later develop leukemia. For example, drugs known as alkylating agents are associated with the development of leukemia many years later. Down syndrome and certain other genetic diseases — Some diseases caused by abnormal chromosomes may increase the risk of leukemia. Children and adolescents with Down's syndrome have a 10 to 30-fold increased incidence of leukemia Human T-cell leukemia virus-I (HTLV-I) — This virus causes a rare type of Chronic Lymphocytic Leukemia known as Human T-cell leukemia.HTLV II – Hairy cell leukemia Chromosomal aberration – observed in ALL & CGL – presence of Philadelphia Chromosome CLASSIFICATION ACUTE • Acute Myeloblastic Leukemia ( AML) • Acute Lymphoblastic Leukemia ( ALL) • Acute Monoblastic Leukemia ( AMOL) CHRONIC • Chronic Lymphocytic Leukemia ( CLL) • Chronic Monocytic Leukemia ( CMOL)

•

Chronic Granulocytic Leukemia ( CGL)

ACUTE LEUKEMIA • • •

• •

• • • • • • • •

• •

•

Found frequently in children and young adults Incidence - 5 out of 100000 Abrupt onset Runs a rapidly fatal course Fever Rapidly developing anemia, thrombocytopenia and hemorrhage Bone pain ( ALL) Lymphadenopathy (ALL) Splenomegaly & hepatomegaly Bleeding gums & bruising Headache,nausea Normochromic normocytic anemia WBC count –normal / raised Blast Cells seen in the peripheral blood Decreased platelet count Bonemarrow hypercellular with characteristic blast cells

TYPES : AML; ALL; AMOL

ACUTE LYMPHOBLASTIC LEUKEMIA ( ALL) • • • • • •

• • •

Proliferation of lymphoblasts WBC count – 20,000 – 1 lakh /cu mm > 50 % of the cells are lymphoblasts They are 1½ times the size of lymphocytes Smudge cells in the peripheral blood smear The most vulnerable section to be affected are children. 1 person per 100,000 affected Anemia, thrombocytopenia,lymphadenopathy & splenomegaly. Bone marrow infiltrated with lymphoblasts 25% adults and 3% children diagnosed with ALL have Philadelphia Chromosome

CLINICAL FEATURES - Fever , sore throat Enlargement of liver, lymph nodes, spleen Bone pain

ACUTE MYELOBLASTIC LEUKEMIA ( AML) • Cell count – 20000-10000/cu mm • Incidence – 1 in 40000 (1in 25,000 people over 50 is at risk from AML, while in the age group of 70 and above 1 in 7000 people is at risk. )

• • • • • • • • • • • • • • • •

Occurs in adults (People over the age of 50) Peripheral blood - 90% blast cells Cytoplasm of these cells blue with vacuoles Nucleus round,2-5 distinct nucleoli Nuclear chromatin – fine Auer rods / bodies – in the cytoplasm Swollen, painful, and bleeding gums - if AML has spread to the oral tissue; Pigmented (colored) rash-like spots - if AML has spread to the skin; Poorly differentiated myeloblasts are present. Some contain azurophil granules, but the percentage of maturing granulocytes is less than 10%. Peroxidase stain reveals the Auer rods Peroxidase stain used to differentiate ALL from AML AML - Peroxidase positive ALL – not Peroxidase positive Sudan Black B - used to differentiate ALL from AML AML – positive; ALL – negative

ACUTE MONOBLASTIC LEUKEMIA ( AMOL) • Leucocyte count –20000 – 1 lakh / cu mm • Promonocyte and monoblast make up 25 -75% of cells • Monoblasts have muddy / smoggy grey-blue cytoplasm with tiny granules • Cytoplasmic protrusions common • Nucleus – indentation / irregularity with 1 – 5 large nucleoli • Nuclear chromatin – reticulogranular • Severe thrombocytopenia, nucleated red cells seen CHRONIC • Occurs in middle aged individuals • Onset is gradual (insidious) • Anemia slow to develop • More differentiated cells • Terminal stages – more blast cells TYPES • Chronic Granulocytic Leukemia ( CGL) • Chronic Lymphocytic Leukemia ( CLL) • Chronic Monocytic Leukemia ( CMOL) CHRONIC LYMPHOCYTIC LEUKEMIA ( CLL) • • •

Disease of middle aged and elderly - cases reported in individuals older than 55 years WBC count – 2 – 2.5lakhs / cu mm 95% small lymphocytes 5% blast cells

• • • • • • • • •

Prolymphocytes are seen Clinical features – fever, lethargy, wt.loss infections Moderate enlargement of lymph nodes Splenic and hepatic enlargement Mild anemia As disease progresses – severe hemolyticanemia develops Benign condition – lasts upto 20years Initial course that is relatively benign but followed by a terminal progressive and resistant phase lasting 1-2 years.

CHRONIC GRANULOCYTIC LEUKEMIA ( CGL) • • • • • • • • • • • • • •

Uncommon form of leukemia Characterized by the presence of Philadelphia Chromosome Occurs in the middle aged and the elderly Highest leucocyte count -4 to 8 lakhs / cu mm 30 -70% neutrophils, 2 – 20% Basophils, 2 – 10% Eosinophils 0 – 10 % are myeloblasts Other myeloid precursors (myelocytes, metamyelocytes) are also found. Leucocyte alkaline phosphatase (LAP) is very low. Level of serum vitamin B12 and B12 binding protein elevated Normal Hb – eventually anemia develops Platelet count normal / slightly elevated Hypercellular marrow CML – slow progression – Enlarged Spleen ( splenomegaly) Survival of about 3 -5years

CHRONIC MONOCYTIC LEUKEMIA • Chronic monocytic leukemia (CMOL) is a poorly documented, rare disease. • Most patients are adults, and present with fever, • Hepatomegaly. Splenomegaly has been a consistent manifestation. • Hematologic findings. CMOL is the only form of human leukemia that usually does not initially appear to present with abnormal circulating cells • Thrombocytopenia and anemia may be present. • Absolute monocytosis may be detected • Monocytes in the peripheral blood have a ground glass or slate grey cytoplasm with a variable number of vacuoles and lilac granules • Nucleus may reveal delicate lace like chromatin, and may be round, oval. • Nucleoli are usually absent or inconspicuous • The Sudan black B reactions are variably positive. • Leucocyte count - 3-70 X 109/L • Pseudopodial protrusions common • Anemia

•

Platelets moderately reduced

------------------------------------------------------------------------------------------------