LEUKEMIADr. Hayam Hebah

Associate professor of Internal MedicineAL Maarefa College

objectives

• Introduction to leukemias• c/p of uremia• Management • AML• ALL

Introduction:

Background and epidemiology:• Leukemias are a group of heterogeneous neoplastic

disorders of stem cell compartment , characterised by increased white blood cells count in bone marrow &/or peripheral blood.

• Leukemias are acute or chronic, based on their untreated course ( course may vary from days or weeks to years).

• Males are affected more than females• Geographical variation occur in incidence• Most childhood leukemias are acute :ALL• Whites are more affected than blacks in ALL & CLL

C/P and DD:

• Acute leukemias usually present as hemorrhage, anemia, infection, or infiltration of organs.

• Chronic leukemias are asymptomatic. Other patients present with splenomegaly, fever, weight loss, malaise, frequent infections, bleeding, thrombosis, or lymphadenopathy.

• Some chronic leukemias enter a blast phase where the clinical manifestations are similar to the acute leukemias.

Diagnosis of leukemia• CBC and differentiaL:• Abnormal blood count( often ↑ WBCs)• Bone marrow examination:1. Abnormal cells : the morphology of blasts usually can differentiate

between ALL & AML.2. Cell surface markers( immunophenotyping) using multiparameter

flow cytometry identifies the B or T cell origin of the lymphoblasts

3. Clone specific chromosome abnormality: philadelphia chromosome in CML .Chromosomal analysis of the leukemic cell currently provides the most important pretreatment prognostic information in AML

4-Molecular changes

ACUTE LEUKEMIAS• AML is 4 times more common in adults > ALL.• In children ALL>AML• Anemia with N or ↑MCV• WBCs 1000-500000/mm³( majority 100000/mm³) • Thrombocytopenia• Blood film :± blasts• BM: hypercellular with replaced normal elements by

leukemic blast cells.(>20%)• Auer rods in blast cell cytoplasm=myeloblastic type

• Fever >38°c>1 h in a neutropenic patient denotes possibility of septicemia.

• Organisms associated with severe neutropenic sepsis: G+ve bact . as Staph aureus, Staph epidermidis from skin via cannulas.

• G-ve infections from GIT• ALL patients are susceptible to Pneumocystis jirovecii and

pneumonia• Oral and pharyngeal candidiasis• Systemic fungal infections• Herpes simplex infection

Management of acute leukemia

Specific therapy• Remission induction• Remission consolidation• Remission maintenance• In ALL:1. cranial irradiation2. intrathecal chemotherapy3. high dose methotrexate

*****Haematopoietic stem cell transplantation

Supportive therapy• Red cell concentrate transfusion• Platelet transfusion• Blood products must be irradiated to

prevent transfusion-associated graft versus host disease (GVHD)

• Broad spectrum antibiotics• Antibiotic prophylaxis during

chemotherapy in ALL• Monitor fluid balance, renal, hepatic

and hemostatic function• Anorexia &diarrhea ttt• TTT of tumor lysis syndrome• Psychological support

Management of metabolic problems.

1. Iv fluids and electrolytes for the anorexia and drinking difficulties.

2. Antibiotics induced renal toxicity as with aminoglycosides and amphotericin.

3. Tumor lysis syndrome during induction therapy with hyperkalemia, hyperuricemia, hyperphosphatemia and hypocalcemia

ACUTE MYELOID LEUKEMIA

Epidemiology:• AML is more in developed countries.• more in whites ,Men> women.• the prevalence of AML increases with age. The median

age of onset is approximately 70 years. However, AML affects all age groups. hematopoietic precursors are arrested in an early stage of development.

• cc by presence of more than 20% blasts in the bone marrow

• AML is divided into categories depending on the morphology

FAB subtypes

• M0: AML minimally differentiated• M1: AML without maturation.• M2:AML with maturation• M3: Acute promyelocytic anemia.• M4: Acute myelomonocytic leukemia• M5: Acute monocytic leukemia• M6: Acute erythroleukemia• M7: Acute megakaryoblastic leukemia

WHO CLASSIFICATION recently

1. AML with recurrent genetic abnormalities( M3 Acute promyelocytic anemia d.t presence of t(15;17).

2. AML with MLD(multilineage dysplasia) prior MDS.

3. AML therapy related 4. AML not otherwise categorised (FAB

subtypes M0,M1,M2,M4,M5,M6,M7)

Etiology:

1. Antecedent hematologic disorders : commonest is myelodysplastic syndrome(patients with high-risk MDS develop AML but those with low risk MDS do not.Also, aplastic anemia. And MPD.

2. Congenital disordersDown syndrome ,congenital neutropenia, Fanconi anemia

3. Familial syndrome with genetic abnormalities: Turner and kleinfelter syndrome.

4. Environmental exposures: radiation exposure, exposure to benzene , smoking.

5-Previous exposure to chemotherapeutic agent: The typical latency period between drug exposure and acute leukemia is approximately 3-5 years for alkylating agents( cyclophosphamide) /radiation exposure, but it is only 9-12 months for topoisomerase inhibitors.**However, most patients who present with de novo AML have no identifiable risk factor.

c/p:• General fatigue , fever, • Symptoms of bone marrow failure :related to anemia,

neutropenia, and thrombocytopenia.• (Patients with AML often have decreased neutrophil levels

despite an increased total white blood cell (WBC) count) (Patients with the lowest absolute neutrophil counts (ANCs) (ie, < 500 cells/µL, especially < 100 cells/µL) have the highest risk of infection.)

• Bleeding may be caused by thrombocytopenia, coagulopathy that results from disseminated intravascular coagulation (DIC), or both.

• Symptoms of organ infiltration with leukemic cells: The most common sites of infiltration include the spleen, liver, gums, and skin( leukemia cutis).

• Patients with markedly elevated WBC counts (>100,000 cells/µL) can present with a medical emergency with symptoms of leukostasis (ie, dyspnea ,chest pain , headache and altered mental status , cranial nerve palsies.

Examination:

• Physical signs of anemia, including pallor and a cardiac flow murmur

• Fever and other signs of infection as pneumonia.• petechiae, particularly on the lower extremities in

thrombocytopenic patients.• Purpura and ecchymosis(with DIC).• hepatosplenomegaly and, to a lesser degree,

lymphadenopathy• Signs relating to leukostasis include respiratory distress

and altered mental status.

Differential Diagnoses

• Acute Lymphoblastic Leukemia• Anemia• Aplastic Anemia• B-Cell Lymphoma• Bone Marrow Failure• Chronic Myelogenous Leukemia• Lymphoblastic Lymphoma• Myelodysplastic Syndrome

• Bone marrow examination: for cytochemistry, flow cytometry and cytogenetics

• Markers for AML include positive myeloperoxidase staining, CD33, CD13, CD41 and glycophorin A.

investigations• CBC: with differential .• Pancytopenia or wbcs >100000/μl• WBCs may be N, ↑ or ↓• Anemia• Thrombocytopenia.• Coagulation studies. DIC with ↑PT, ↓fibrinogen and ↑FDPs.• Peripheral blood smear Circulating blasts are usually

seen> 20%• Blood chemistry profile

Chemotherapy for Acute Myelogenous Leukemia

• Induction therapy: Cytarabine for 7 days and an anthracycline for 3 days

• Consolidation therapy in younger patient may be effective but in old age >75 years there is usually poor response

• Stem cell transplantation• Supportive Care:1. Replacement of blood products2. Antibiotic therapy3. Treatment of hyperuricemia4. Growth factors( G-CSF)

ACUTE LYMPHOBLASTIC LEUKEMIA

ACUTE LYMPHOBLASTIC LEUKEMIA

• Acute lymphocytic leukemia (ALL) is a malignant clonal disorder of the bone marrow lymphopoietic precursor cells. In ALL, progressive medullary and extramedullary accumulations of lymphoblasts are present that lack the potential for differentiation and maturation. An inhibition of the normal development of hematopoietic cell elements occurs.

• Bimodal age distribution , one peak at 4-5 years and second increase after 50 years.

• 3 subtypes: precursor B cell , mature B cell( Burkitt lymphoma ) and T cell

• Philadelphia chromosome may be present

The clinical presentation

1. progressive weakness and fatigue, fever and bleeding ( When 50% of BM is replaced, then peripheral blood cytopenias are observed)

2. Extremity joint pain may be the only manifestation in children.

3. lymphadenopathy and splenomegaly4. Leukostasis is uncommon5. CNS may be involved6. ALL associated with anterior mediastinal mass( in T

cell subtypes ) or large abd. LN ( in B cell type).

diagnosis

• Basic workup• BM hypercellular, blasts>30%• 30% of adult patients exhibit ph. Chromosome• Treatment:1. Induction, consolidation,and maintenance for 2

years.2. Because of CNS , prophylactic intrathecal therapy

during induction and consolidation phases.3. Allogenic stem cell Tx.

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