LEUKEMIA

Leukemias ↑ leukocytes

Acute leukemias

1. Acute Lymphoblastic Leukemia (ALL)2. Acute Myelogenous Leukemia (AML)

Chronic leukemias

1.Chronic Lymphoblastic Leukemia (CLL)

2. Chronic Myelogenous Leukemia (CML)

Acute Leukemias Blast predominate Child or elder Short & drastic course ALL – Lymphoblasts (pre-B or pre-T) AML – Myeloblasts

Chronic Leukemias More mature cells Middle age Longer & less devastating course CLL – Lymphocytes CML – Myeloid stem cells

Acute Leukemias accumulation of blasts in the marrow

Acute Lymphoblastic Leukemia (ALL)

Children Lymphoblasts (pre-B or pre-T) Neoplastic transformation of the

lymphoid stem cells• Progressive accumulation of

Lymphoblasts in the bone marrow

• Suppression of normal hemopoiesis

ALL

• Primarily a disease of children and young adults

• B-cell subtype (80%)• T-cell subtype (20%)

ALLAbrupt onsetSigns and symptoms related to:

• Suppression of normal hemopoiesis

bone pain and tenderness• Tissue infiltration ( megaly)

(lymph nodes, spleen, liver, testicles, CNS)• Mediastinal mass ( T-ALL ) thymus involvement

Headache, vomiting, nerve palsies from meningeal spread.

Signs &Symptoms Anemia Infection Bleeding Bone pain Arthritis Splenomegaly Lymphadenopathy CNS involvement

ALL - PROGNOSISFavorable: Unfavorable:Pre-B T or mature B Age 3-7 < 1, > 10WBC < 10 000/uL > 50 000/uLFemale MaleMinimal organ Prominent

organinvolvement involvement

ALLPrognosis:

• Age 3-7, pre-B, > 90% - CR ( 2/3 - cure )

• Adults, mature B and T-ALL:Less favorable

Therapy: Chemotherapy supportive care, BMT

ACUTE MYELOGENOUS LEUKEMIA ( AML )

- Adults- Myeloblasts- monoblasts, eosinoblasts,

megakarioblasts, proerythroblasts, basophiloblasts

- Auer rods in the cytoplasm of the cells- Very rapidly progressive malignancy

AML

Auer rods in AML

Differentiation from ALL may be made by microscopy – presence of Auer Rods.

Can also be made based on immunotyping and molecular methods.

Clinical features based on Marrow failure –anemia, bleeding,

DIC, infection… Leukemic infiltration – bone pain,

CNS signs, hepatosplenomegaly, lymphadenopathy…

Constitutional upset -- malaise, fever, weakness, polyarthritis.

Course:• Rapidly fatal if untreated (< 2 mo )• Median survival - 3 years after chem..• Adverse prognostic factors:

Age > 60 Previous chemotherapyLeukocytosis > 100,000 /ul

Therapy: Chemotherapy, supportive, BMT

***Remember this*** For Acute leukemias

acute leukemias = too many blasts in the marrow

2 broad categories: AML vs. ALL a hematologic urgency prognosis is poor in adults; but good

in kids with ALL.

CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)

A monoclonal lymphoproliferative disorder characterized by lymphocytosis(>4000/cu.mm),lymphadenopathy and splenomegaly

B - CLL > 95%T - CLL

CLL

• Most common adult leukemia in Western society (30% of all leukemias)

• Monoclonal proliferation of the small lymphocytes…

• Age > 40 M:F / 2:1

CLL - PathologyBlood:

• Lymphocytosis( > 10,000 u/L - diagnostic )

• (+) Coombs test (20%)• Hypogammaglobulinemia (50-70%)• Anemia, thrombocytopenia, neutropenia

Bone marrow:• nodular / interstitial infiltrates• diffuse - obliteration of normal hemopoiesis

Lymphadenopathy, Hepatosplenomegaly(50-60%)

CLL - Clinical course

Initially: asymptomaticAdvanced disease:

• bacterial infections, hemorrhage

Prognostic factors:• extent of tumor burden• pattern of marrow infiltration• chromosomal abnormalities

Median survival: ~ 6 years

CLL - Course

• CONVERSION TO PROLYMPHOCYTIC LEUKEMIA

(10%)

• RICHTER SYNDROME (5%)(AGGRESSIVE LYMPHOMA)

• DEATH OFTEN DUE TO INFECTIONS..

Smudge cells - CLL

CLL One more peripheral blood findings

in CLL is Presence of Smudge cells

( parachute cells). Along with increased number of

normal appearing lymphocytes.

mainly uncontrolled proliferation of myeloid cells.

Males more than females

Splenomegaly – sometimes massive..

**Philadelphia chromosome** Hybrid chromosome with

translocation between the long arm of chr. 9 and long arm of chr.22 . --- t(9:22).

May be present in granulocyte, RBC or platelet precursors in more than 95% of CML..

Absence of these chr. may have worse prognosis.

CML - Clinical Features

15 - 20% of all leukemias; age 25-60Symptoms:

- non-specific- related to hypermetabolism (high cell turnover)- related to splenomegaly

Course:- chronic phase (mean survival, 3-4y)- accelerated phase- blast crisis / myeloid or lymphoid (survival, < 1y)

Therapy: chemotherapy; BMT

CML: Sustained granulocytosis with immature cells; low LAP score; bone marrow pathology;

Philadelphia chromosome LAP – leukocyte alkaline phosphatase