Acute & Chronic Myeloid Leukemias

• Acute & Chronic Myeloid Leukemias neoplastic cells of the hemopoietic system

Acute & Chronic Myeloid Leukemias ,The myeloid leukemias are a group of diseases with infiltration of blood, bone-marrow and other tissues by neoplastic cells of the hemopoietic system

Acute & Chronic Myeloid Leukemias

Acute & Chronic Myeloid Leukemias

• The myeloid leukemias are a group of diseases with infiltration of blood, bone-marrow and other tissues by neoplastic cells of the hemopoietic system.

ACUTE MYELOID LEUKEMIA

• Incidence is higher in men than in women. Incidence increases with age.

Etiolog

Acute & Chronic Myeloid Leukemias Etiology —

• Heredity, radiation, chemical and occupa­tional exposure, drugs, virus.
• Certain syndromes are associated with leukemias like Down’s syndrome, Klinefelter syndrome, Patau syn­drome, Fanconi anemia, Ataxia telangiectasia, Kostmann syndrome.

Acute & Chronic Myeloid Leukemias Classification —

• Acute leukemias are classified on basis of morphology, cytochemistry, cytogenetics and molecular techniques.

Clinical presentation Acute & Chronic Myeloid Leukemias

• Patients with AML(acute myeloid leukemia) present with non-specific symp­toms, gradually or abruptly.
• Presentation may be due to anaemia, leukocytosis, leukopenia, or thrombocytopenia.

Acute & Chronic Myeloid Leukemias Symptoms —

• are fatigue, weakness, anorexia, weight loss, fever, bleeding, easy bruising, bone pains, lym­phadenopathy, cough, headache, diaphoresis.

Acute & Chronic Myeloid Leukemias Physical findings —

• are fever, splenomegaly, hepatomegaly, lymphadenopathy, sternal tenderness, infection, haemorrhage, GI (gastrointestinal) bleed­ing, intracranial haemorrhage, retinal hemorrhages.
• There may be infiltration of gums, skin, soft tissues, meninges, granulocytic sarcoma in GIT, lung, uterus, breast, prostate, mediastinum, and bone.
• Other systems
• which are involved are cardiovascu­lar, hepatic and renal systems.
• The most severe and fatal presentation is in acute promyelocytic leukemia (APL) or monocytic AML.

Hematological findings

Hematological findings

• Anaemia – usually normocytic, normochromic. Reduced reticulocyte count.
• Leukocyte count may be 15,000 to 100,000 or some­times more than even 100,000/1J1.
• 20 – 40 per cent of patients have leucocyte count less than 5000/1J1.

FAB (French-American-British) classification of AML

• MO M1 M2 M3 M4 M4Eo
• Minimally differentiated leukemia Myeloblastic leukemia without maturation Myeloblastic leukemia with maturation Hypergranular promyelocytic leukemia Myelomonocytic leukemia
• Variant: Increase in abnormal marrow eosinophils
• Monocytic leukemia
• Erythroleukemia (DiGuglielmo’s disease) Megakaryoblastic leukemia

Acute & Chronic Myeloid Leukemias Treatment

• The treatment is divided into 2 phases:
• Induction phase
• Post remission management
• The goal is to quickly induce CR (complete remis­sion).

Complete remission (CR)

• CR is defined as absence of blast cells in circulation. Blood neutrophil count must be more than 1500/1J1. Platelet count must be more than 100,000/ IJI. Bone-marrow should contain less than 5% blast cells. Auer rods should be absent.
• Standard therapy is 7-day continuous infusion of Cytarabine 100 – 200 mg /sq m / day.
• Patients who achieve CR must be given consolidation therapy with sequential courses of Cytarabine in high doses and allogenic stem cell transplant.
• Patients with APL (acute promyeiocytic leukemia) should receive Tretinoin with anthracycline chemo­therapy (Daunorubicin), and then consolidation che­motherapy with Daunorubicin and Cytarabine, fol­lowed by maintenance with tretinoin.
• Clinical trials with recombinant hemopoietic growth factors are going on.

Acute & Chronic Myeloid Leukemias Supportive care

• with blood transfusion, platelet transfusion, broad-spectrum antibacterials, and an­tifungals are given.

CHRONIC MYELOGENOUS I MYELOID LEUKEMIA

• The diagnosis ofCML(chronicmyeloid leukemia) is by presence of haematopoietic stem cell with recip­rocal translocation between chromosomes 9 and 22.
• The disease is characterized by elevated white blood cell counts with a majority of immature granu­locytes, which progresses to an accelerated phase and a blast crisis.
• The incidence of CML increases after the age of 40.

Etiology is same as AML

• Clinical presentation Onset is slow, with patients often asymptomatic at diagnosis.
• There is fatigue, malaise, weight loss, splenomegaly, infections, thrombosis, bleeding, cerebrovascular ac­cidents, MI, venous thrombosis, bone and joint pains, splenomegaly, hepatomegaly, lymphadenopathy.

Acute & Chronic Myeloid Leukemias Hematological findings

• White blood cells counts are grossly elevated, imma­ture granulocytes are seen in circulating blood, but small in number i.e. less than 5% blasts and less than 10% promyelocytes are seen in circulating blood.
• Platelet counts may be elevated
• There is increased bone marrow cellularity, of my­eloid and megakaryocytic types.
• Disease acceleration is defined as increasing anaemia, blood or marrow blasts between 10 and 20%, blood or marrow basophils >20%, platelet count less than 100,000/1-11.
• Blast crisis is defined as acute leukemia with blood or marrow blasts more than 20%.

Acute & Chronic Myeloid Leukemias Treatment

• Allogenic stem cell transplant or treatment with ImatinibInterferon
• Chemotherapy with hydroxyurea, 1-4 g/day, halved when leucocyte count reduces by 50%
• Busulphan : alkylating agent, with serious side­effects and therefore not used nowadays
• HHT — Homoharringtonine is a plant alkaloid from Cephalotaxus tree
• Leukapheresis and splenectomy