Introduction To Haematological Malignancies

By Tiffany Shaw

MBChB II

July 2002

Common Malignancies

Acute Chronic

Lymphoid Acute lymphoblastic leukemia

Chronic lymphocytic leukemia

Lymphoma

Myeloma

Myeloid Acute myeloid leukemia Chronic myeloid leukemia

Acute Leukemias -- Definition

A malignant disorder in which haemopoietic blast cells proliferate and constitute > 30% of the bone marrow.

Lymphoblasts Lymphoblastic leukemia

Myeloblasts Myeloid leukemia

Acute Leukemias -- PC

1. Bone marrow infiltrated by blasts cells2. Bone marrow failure3. Pan-cytopenia4. Anaemia fatigue, SOB on exersion5. Thrombocytopenia bleeding / DIC6. Neutropenia infections7. Constitutional symptoms (malaise,

anorexia, night sweat, fever)8. Lymphadenopathy, hepatospenomegaly

Acute Leukemias -- Ix

1. Low Hb

2. Low platelets

3. High WCC (increased blast cells)

4. Low neutrophils

5. Elevated serum uric acid

6. Bone marrow biopsy: infiltration by blast cells

Acute Leukemias – Risk Factors

Familial

Down’s syndrome

Viral infection (EBV Burkitt’s)

Radiation

Chemotherapy

Acute Leukemias – AML VS ALL

AMLMyeloblastic

Any age

1/3 transformation from other myeloproliferative disorders

Increased DIC

ALLLymphoblastic

Commonly children

Primary event

More lymphadenopathy and hepatosplenomegaly

Acute Leukemias -- Classification

French-American-British Classification

Morphology

Cytochemistry

Immunophenotype

Cytogenetics

DNA analysis

Examples

AML

Promyelocytic

Myelomonocytic

Monocytic

Erythroid

Megakeryoblastic

Undifferentiated

…. ect.

ALL

Small cells

Large cells

Vacuolated basophillic blast cells

Acute Leukemias -- Mx

Supportive Rx

Anaemia: blood transfusion prn

Bleeding: platelets prn

Infection: antibiotics prn

Social support + issues

Acute Leukemias -- Mx

Chemotherapy:

Remission-induction phase

Consolidation phase

Maintenance phase (for ALL)

prednisone, daunorubicin, vincristine, thioguanine, cyclophosphamide…

Acute Leukemias -- Mx

Bone Marrow Transplantation:

High-dose chemo Rx

Removal of stem cells from donor

Transplantation into recipient

Acute Leukemias -- Prognosis

AML

~ 30-40% cured

Varies widely with age, co-morbidity..etc.

ALL

In children, ~ 70% cured

In adults, ~ 30-40%

Chronic Myeloid Leukemia

Increase in neutrophils and their precursors

Really a myeloproliferative disorder

> 95% patients have chromosomal mutation --- Philadelphia chromosome

CML -- PC

Constitutional symptoms (anorexia, weight loss, fatigue, night sweat)

Splenomegaly (hypochondrial pain)

Asymptomatic – incidental finding

CML -- Ix

Increased WCC (neutrophils and precursors)Later bone marrow failure (anaemia + thrombocytopenia)Raised serum B12Raised serum uric acidBone marrow biopsy hypercellular with high myeloid:erythroid ratio

CML – Course/Progression

Chronic PhaseRaised WCCConstitutional symptoms / Asymptomatic

Accelerated PhaseAnaemia + thrombocytopeniaSplenomegalyBone marrow fibrosis

Acute PhaseTransformation to acute leukemia (80% AML, 20% ALL)

CML -- Mx

Chronic PhaseHydroxyurea

Interferons

Chemo Rx

Bone marrow transplantation

Acute PhaseSame as acute leukemia

Chronic Lymphcytic Leukemia

Increased lymphocytes (B cells) in the blood, bone marrow, lymph nodes, and spleen.

Lymphoproliferative disorder

CLL -- PC

Asymptomatic

Lymphadenopathy

Constitutional symptoms (night sweat, weight loss, anorexia)

Symptoms of bone marrow failure

Splenomagaly

CLL -- Ix

Lymphocytosis (B cells)

Low serum Ig

Raised serum uric acid

Bone marrow biopsy lymphocytic infiltration

CLL -- Ix

Depends on stage:

Stage A B C

< 3 lymph node groups involvement

Bloods normal

> 3 lymph node groups involvement

Bloods normal

Bloods abnormal (anaemia + thrombocytopenia)

CLL -- Mx

1. Observation (stage A)

2. Chlorambucil PO (lower lymphocyte count and lymphadenopathy)

3. Corticosteroid

4. Fludarabine IV

5. Other chemo Rx

6. Supportive care

CLL -- Prognosis

Variable

May remain stationary or progress

Some stay asymptomatic for > 10 years

Cause of death = bone marrow failure, infiltration of other organs