Showing posts with label Haematology. Show all posts
Showing posts with label Haematology. Show all posts

Thursday, May 26, 2011

CHRONIC MYELOID LEUKAEMIA





Leukaemias

What are Leukemias

Neoplasm of white blood cell and its precursor

Clonal proliferations and accumulation of cells in marrow

Classify as

· Acute leukaemias

· Chronic leukaemias

Types of Leukaemia

Introduction- CML

· Clonal malignant myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate

· Results in increases in myeloid cells, erythroid cells and platelets in peripheral blood and marked myeloid hyperplasia in the bone marrow


· Originate in a single abnormal haemopoietic stem cell

· Incidence :1 per 100,000 (UK)

· Accounts for 7-15% of all leukaemia in adults

· Median age : 53 years

· All age groups, including children, can be affected

Etiology

· Not clear

· Little evidence of genetic factors linked to the disease

· Increased incidence

o Survivors of the atomic disasters at Nagasaki & Hiroshima

o Post radiation therapy

Leukaemogenesis

· Philadelphia chromosome is an acquired cytogenetic anomaly that is characterizes in all leukaemic cells in CML

· 90-95% of CML pts have Ph chromosome



· Reciprocal translocation of chromosome 22 and chromosome 9

· BCR (breakpoint cluster region) gene on chromosome 22 fused to the ABL (Ableson leukemia virus) gene on chromosome 9

· Ph chromosome is found on myeloid, monocytic, erythroid, megakaryocytic, B-cells and sometimes T-cell proof that CML derived from pluripotent stem cell

· Molecular consequence of the t(9;22) is the fusion protein BCR–ABL, which has increased in tyrosine kinase activity

· BCR-ABL protein transform hematopoietic cells so that their growth and survival become independent of cytokines

· It protects hematopoietic cells from programmed cell death (apoptosis)

Clinical Features

o Disease is biphasic, sometimes triphasic

o 40% asymptomatic

o Chronic phase

o Splenomegaly often massive

o Symptoms related to hypermetabolism

o Weight loss

o Anorexia

o Lassitude

o Night sweats

o Features of anaemia

o Pallor, dyspnoea, tachycardia

o Abnormal platelet function

o Bruising, epistaxis, menorrhagia

o Hyperleukocytosis

o thrombosis

o Increased purine breakdown : gout

o Visual disturbances

o Priapism

o Lab features


o Peripheral blood film

o Anaemia

o Leukocytosis (usu >25 x 109/L, freq> 100 x 109/L

o WBC differential shows granulocytes in all stages of maturation

o Basophilia

o thrombocytosis

o Bone marrow

o Hypercellular (reduced fat spaces)

o Myeloid:erythroid ratio – 10:1 to 30:1 (N : 2:1)

o Myelocyte predominant cell, blasts less 10%

o Megakaryocytes increased & dysplastic

o Increase reticulin fibrosis in 30-40%

o Other lab features :

o NAP reduced

o Serum B12 and transcobalamin increased

o Serum uric acid increased

o Lactate dehydrogenase increased

o Cytogenetic : Philadelphia chromosome

Laboratory- summary

Lab investigation to confirm diagnosis

Full blood picture

Neutrophil alkaline phosphatase

Bone marrow cytogenetic

Phases

Accelerated phase

Median duration is 3.5 – 5 yrs before evolving to more aggressive phases

Clinical features

Increasing splenomegaly refractory to chemo

Increasing chemotherapy requirement

Lab features

Blasts>15% in blood

Blast & promyelocyte > 30% in blood

Basophil 20% in blood

Thrombocytopenia

Cytogenetic: clonal evolution

Phases

Blastic phase


Resembles acute leukaemia

Diagnosis requires > 30% blast in marrow

2/3 transform to myeloid blastic phase and 1/3 to lymphoid blastic phase

Survival : 9 mos vs 3 mos (lym vs myeloid)

General Management

o Discussion with family

o The disease & diagnosis

o Prognosis

o Choices of treatment

§ Cytotoxic drug vs bone marrow transplant

§ Side effect

o CML - principles of treatment

o Relieve symptoms of hyperleukocytosis, splenomegaly and thrombocytosis

o Hydration

o Chemotherapy (bulsuphan, Hydoxyurea)

o Control and prolong chronic phase (non-curative)

o alpha interferon+chemotherapy

o imatinib mesylate

o chemotherapy (hydroxyurea)

o CML - principles of treatment

o Treatment cont…

o Eradicate malignant clone (curative)

o allogeneic transplantation

o alpha interferon ?

o imatinib mesylate/STI 571 ?(Thyrosine kinase inhibitor)

o Chemotherapy

o Busulphan

o Alkylating agent

o Preferred in older pts (not candidate for transplant)

o Side effect :

§ prolonged myelosuppression

§ Pulmonary fibrosis

§ Skin pigmentation

§ infertility

o Chemotherapy

o Hydoxyures

o Fewer side effect

o Acts by inhibiting the enzyme ribonucleotide reductase

o Haematological remissions obtain in 80% for both drugs

o However disease progression not altered and persistence of Ph chromosome containing clone

o Chemotherapy

o Recombinant human α- Interferon

o Prolong chronic phase and increase survival

o Haematogical and cytogenetic remission

o Side effect

§ Flu like symptoms

§ Fever and chills

§ Anorexia

§ Depression

o CML - prognosis

o Median survival 3.5 yrs (range 2-8 yrs)

o Interferon + chemotherapy :6 years

o Transplant : 5+ years

o imatinib mesylate ?

Tuesday, May 3, 2011

Anaemia


Reduced haemoglobin level below the reference level for the age and sex of the individual

CAUSES OF ANAEMIA

« Nutritional

« Reduced absorption

« Blood loss

« Haemolysis

« Bone marrow suppression Chronic infection

« Other chronic diseases

CLINICAL FEATURES OF ANAEMIA

« Fatigue

« Headache

« Faintness

« Breathlessness

« Angina

« Intermittent claudication

« Palpitations

« May be asymptomatic

SIGNS

1. Pallor

2. Tachycardia

3. Bounding pulse

4. Systolic flow murmur

5. Evidence of cardiac failure

Rarely, Papilloedema,

Retinal haemorrhages

SPECIFIC SIGNS

Signs of Nutritional deficiency +

Koilonychia (Fe Deficiency)

Jaundice (Haemolytic anaemia)

Bone deformities (Thalassaemia)

Leg ulcers (Sickle cell disease)

Lymphadenopathy/Hepatosplenomegal

(Myeloproliferative/lymphoproliferative disorders)

Telengiectasia

(Hereditary haemorrhagic telengiectasia)

INVESTIGATIONS

ü Hb level

ü WBC count

ü Platelet count

ü Reticulocyte count (Indicates marrow activity)

ü Blood picture (indicated probable aetiology)

ü Bone marrow

TYPES OF ANAEMIA

According to the blood picture,

HYPOCHROMIC MICROCYTIC ANAEMIA

ü Iron deficiency anaemia

ü Thalassaemia



NORMOCHROMIC NORMOCHROMIC ANAEMIA

ü Anaemia of chronic disease

MACROCYTIC ANAEMIA

ü Vit B12, Folate deficiency

DIAMORPHIC BLOOD PICTURE

ü Mixed deficiency or following treatment

IRON DEFICIENCY ANAEMIA

(Hypochromic microcytic anaemia)

CAUSES

« Blood loss

« Decreased absorption

« Poor intake

« Increased demand

(Growth, Pregnancy)

HISTORY

« Detailed dietary history

« Menstrual history

« Evidence of chronic infection

« Possibility of GI haemorrhages

« Drugs – NSAIDs

CLINICAL FEATURES

FEATURES OF ANAEMIA +

¦Brittle nails

¦Koilonychia (spoon shaped nails)

¦Atrophy of the papillae of the tongue

¦Angular stomatitis

¦Brittle hair

¦Dysphagia and Glossitis

¦(Plummer vinson/kelly patterson)

INVESTIGATIONS

· Blood counts and Red Cell Indices

MCV <80 fl Microcytic

MCH <27 pg Hypochromic

· Blood picture

Hypochromic microcytic with poikylocytosis (variation in shape) and anisocytosis (variation in size)

· Serum Fe â

· Total iron binding capacity (TIBC) á

· Transferrin

saturated

Low serum ferritin confirms the diagnosis

Normal level : Male = 30-300u

Female = 15-200u

Bone marrow is not needed to diagnose iron deficiency anaemia

Other causes of hypochromic microcytic anaemia

· Thalassaemia

· Anaemia of chronic diseases

Treatment

· Find out and treat the underlying cause

· Oral iron therapy

(ferrous sulphate 200mg tds)


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