Leucocyte disorders

Department of Internal Medicine

RGW
 Scanning EM

• Blood is
examined in a
“smear”
• Smears are
stained

Light microscope
2
Blood stem cells divide into:
1. myeloid stem cells
2. lymphoid stem cells
All except for
lymphocytes
arise from
myeloid stem
cells

All originate
in the bone
marrow

Not shown are

mast cells,
osteoclasts,
dendritic cells 3
 WBC Normal values:
• WBC Count = 5,000 – 10,000/cu mm or
5 – 10 x 109/L
• Differential Count:
• Neutrophil = 50 – 70 %
• Segmenter = 50 – 65 %
• Stab = 0 – 5 %
• Eosinophil = 0 – 3 %
• Basophil = 0 – 1 %
• Lymphocytes = 20 – 40 %
• Monocytes = 2 – 6 %
 Quantitative abnormalities
• Leucocytosis – substantial increase in the
WBC count.
- Physiologic increase (no trauma/injury)
- Pathologic increase (trauma/pathology)
• Leucopenia – substantial decrease in the
WBC count.
• N.V. = 5,000 – 10,000/cu mm
 WBC functions
• Neutrophil – phagocytic
• Eosinophil – phagocytic and damage to
larval stages of parasite.
• Basophil – storage of histamine, involved
in immediate hypersensitivity reaction.
• Monocyte – phagocytic, cellular and
humoral immunity
 Cross talk
• Hematologic manifestation of systemic
disease
• Systemic manifestation of hematologic
disease
The 5 WBC types
 Neutrophilia
(> 7 – 8 x109/L)
• Infections, Inflammation, Metabolic
disorders
• Acute hemorrhage, corticosteroids
• Stress, post-surgery, burns, HDN
• Lithium drugs, neoplasms
 Neutropenia
(<1.75 – 1.8109/L)
• Decreased production
- Inherited/acquired stem cell disorder
- Benzene toxicity, cytotoxic drugs
• Increased destruction
- Immune mechanism, sequestration
• BM depression, IM, varicella, Typhoid
• SLE, hepatitis or any viral infections
 Eosinophilia
(> 0.7 x 109/L)
• Allergic disorders (asthma)
• Parasitic infections (nematodes)
• Skin disease (eczema)
• Hodgkin’s disease
• Scarlet Fever
• Pernicious anemia
 Eosinopenia
(< 0.05 x 109/L)
• Stress due to trauma or shock
• Mental distress
• Cushing’s syndrome
• ACTH administration
 Basophil (0.3 x 109/L)

BASOPHILIA Chronic myelocyic leukemia

Polycythemia vera
Hodgkin’s disease

BASOPENIA Hyperthyroidism
Pregnancy
 Lymphocytosis
(>4.0 x 109/L)
• Viral infections ( German measles )
• Infectious Mononucleosis (kissing dis.)
• Mumps (parotitis), pertussis
• Tuberculosis, syphilis, thyrotoxicosis
 Lymphopenia
• Congestive heart failure, SLE
• Renal failure
• Advanced Tuberculosis
• High levels of adrenal corticosteroids
 Monocytosis
(>0.9 x 109/L)
• SBE, Syphilis, Tuberculosis
• Protozoan infections
• Mycotic or fungal infections
• Malaria, Systemic lupus erythematosus
• Rheumatoid arthritis
 Non-clonal disorders of WBC
Function disorders
Defective chemotaxis, phagocytosis,
defective killing, myeloperoxidase
deficiency
Quantitative disorders
Neutropenia, agranulocytosis, Leukemoid
reaction, Infectious mono
Clonal (neoplastic) disorders of
WBC
• Derived from a single precursor cell with
all the affected cells (progeny) showing
features of deviation from the precursor
cell.
• Myeloproliferative disorders
• Lymphoproliferative disorders
• Immunoproliferative disorders
 Leukemoid reaction
• High WBC count = <50000/cu mm
• Toxic granulation & Dohle bodies
• Predominant band forms
• LAP score = >100
• Negative for Philadelphia chromosome
- Translocation of genetic material from long
arm of Chromosome 22 to Ch 9
HEMATOLOGICAL malignancy

Leukemia, Malignant lymphoma

 OUTLINE
• Leukemia
Acute vs Chronic
Lymphoid vs Myeloid
• Lymphoma
Hodgkin’s lymphoma
Non Hodgkin’s lymphoma
• Plasma cell disorders
Multiple myeloma
Waldenström macroglobulinemia
 WHAT IS LEUKEMIA ?
• Disease of the bone marrow and blood

• Abnormal proliferation of blood cells

• Major types:
acute vs chronic
lymphoid vs myeloid
 ACUTE VS CHRONIC
• Acute:
Rapid onset
Fatal if not treated immediately

• Chronic:
Takes months to years to progress
Monitoring disease maybe an option
before treatment
LYMPHOID VS MYELOID
• Lymphoid cells affected:

Lymphoid leukemia

• Myeloid cells affected:

Myeloid leukemia
MAJOR TYPES OF LEUKEMIA

• Acute lymphocytic leukemia

• Acute myeloid leukemia

• Chronic lymphocytic leukemia

• Chronic myeloid leukemia

 Leukemia

acute chronic
HCT

WBC N

Plt N
 Leukemia

acute chronic
 Leukemia

acute chronic
Auer rod
 Leukemia

acute chronic
ALL
CML
AML
CMMoL
APL
AMMoL CLL

AMoL
ALL (L1)
ALL (L2)
Auer rod

ANLL
Acute promyelocytic leukemia
AMoL
WHAT ARE THE SYMPTOMS ?
• Bone marrow failure
Anemia
Infection
Bleeding

• Infiltration of organs other than the

bone marrow

• Symptoms related to the specific type

of leukemia
 TREATMENT

• Chemotherapy
• Biological treatment
• Targeted therapy
• Radiotherapy
• Stem cell transplantation
 CHEMOTHERAPY

• Multiple drugs
Effective
Non selective
Toxic

• Different methods of administration

IV, IM, SC, IT, oral
BIOLOGIC AGENTS

Interferon

Growth factors

Monoclonal antibodies
TARGETED THERAPY
ATRA

Imatinib

Monoclonal antibodies

Proteosome inhibitors

Demethylators
 RADIOTHERAPY

Prophylactic CNS radiotherapy

CNS radiotherapy for treatment

“As needed”
STEM CELL TRANSPLANTATION

PB vs BM vs umbilical cord

Allo vs auto

Related vs unrelated donor

Classic vs mini allo

 TREATMENT

• Acute myeloid leukemia:

Induction
Consolidation
CNS prophylaxis ?
± Maintenance
 TREATMENT

• Acute lymphoid leukemia:

Induction
Consolidation/Intensification
CNS prophylaxis
Maintenance
 TREATMENT

• Chronic myeloid leukemia

Targeted therapy
Biologic agents
Chemotherapy
“Stem cell transplantion”
 TREATMENT

• Chronic lymphoid leukemia

“Watchfull waiting”
Chemotherapy
Biologic agents/targeted therapy
Stem cell transplantion ?
WHAT IS LYMPHOMA ?

Cancer of the lymphatic system

Hodgkin’s lymphoma
Non Hodgkin’s lymphoma
WHAT ARE THE SYMPTOMS ?

• Lymph node enlargement

• Systemic: Fever, night sweats,

weight loss

• Local: Symptoms related to

spesific site involved
DIAGNOSIS AND STAGING
• Biopsy

• Evaluation of the extent of disease

Physical examination
Blood tests
Radiology
Bone marrow biopsy
Special tests as required
PET scan ?
TREATMENT: HODGKIN’S LYMPHOMA

• Primary treatment:
Radiotherapy
Combination chemotherapy ± radiotherapy

• Relapse:
New drug combinations
Radiotherapy
Stem cell transplantation
TREATMENT: NON HODGKIN’S
LYMPHOMA

• Primary treatment:

“Watchful waiting” for low grade NHL

Local treatment: surgery vs radiotherapy

Combination chemotherapy
± Monoclonal antibody
± Radiotherapy
 TREATMENT: NON HODGKIN’S
LYMPHOMA

“Depends on type, grade and stage

of lymphoma”
TREATMENT: NON HODGKIN’S
LYMPHOMA
• Relapse:

New drug combinations

Radiotherapy
High dose chemotherapy
Stem cell transplantation
Radioimmunotherapy
End of slides
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