SlideShare ist ein Scribd-Unternehmen logo
1 von 29
08/02/2023 1
ACUTE LYMPHOBLASTIC
LEUKAEMIA
ANGAI A.H
Outline
Introduction
Definition
Epidemiology
Aetiology
Pathogenesis
Classification
Clinical features
Laboratory investigations
Differential diagnosis
Treatment
Prognosis
Conclusion
INTRODUCTION
Leukaemias are a group of disorders characterized by the accumulation of
malignant white cells in the bone marrow and blood. These abnormal cells
cause symptoms because of
(i) bone marrow failure (e.g. anaemia, neutropenia, thrombocytopenia); and
(ii) infiltration of organs (e.g. liver, spleen, lymph nodes, meninges, brain, skin
or testes).
Definition
Leukaemias are malignant neoplasms of the haemopoietic
stem cell characterized by excessive clonal proliferation and
diffuse replacement of the bone marrow by the neoplastic cells
with spilling over into the peripheral blood and organ infiltration.
They are classified broadly into;
1. Acute Leukaemias
2. Chronic Leukaemias
Acute Leukaemias
Acute Leukaemias are malignant clonal disorders originating in
haematopoietic stem cells or its committed progenitors characterized
by the proliferation of poorly differentiated blast (immature) cells in the
bone marrow and subsequent spillage into the peripheral blood and
tissues.
Acute leukaemias are usually aggressive diseases and are normally
defined by the presence of over 20% of blast cells in the blood or bone
marrow at clinical presentation.
Acute Leukaemias are further subdivided into
i. Acute myeloblastic leukaemia (AML) and
ii. Acute lymphoblastic leukaemia (ALL).
AML is a malignant neoplasm of haematopoietic stem cells originating in bone
marrow and characterised by proliferation of blast cells of myeloid lineage.
ALL is a malignant neoplasm of haematopoietic stem cells of lymphoid lineage
arising from the bone marrow.
Epidemiology
ALL is the most common haematologic malignancy of childhood.
 Highest at 3- 7 years with 75% of cases occurring before the age
of 6 with a secondary rise after the age of 40.
Males are frequently more affected than females.
Aetiology of ALL
Unknown
Various factors associated with increased risk of acute leukaemias
include:
i) Genetic factors
Inherited susceptibility
Association with congenital or hereditary syndromes-e.gDown’s
syndrome (20 times increased incidence),Bloom’s
syndrome,Fanconi’s syndrome,Klinfelter’s syndrome,Ataxia
telangiectasia,Osteogenesis imperfect,Wiskott-Aldrich
syndrome,Diamond- Blackfan syndrome,Kostmann’s syndrome
etc
ii). Acquired conditions include;
Aplastic anaemia
Myelodysplastic syndrome (MDS)
Paroxysmal nocturnal haemoglobinuria (PNH)
Myeloproliferative neoplasms (MPN)
iii). Environmental factors include;
Chemicals – chronic exposure to benzene.
Radiation – radiation to the marrow is leukaemogenic. Also , paternal irradiation
has been identified as a risk factor. Radiation may be natural UV light, diagnostic or
therapeutic
Viral infections – HTLV causing ATLL, EBV causing Burkitt’s lymphoma/Leukemia
Drugs – Alkylating agents e.g. Chlorambucil, Melphalan, Etoposide
Infections – children with less exposure to infection particularly of a high social
class have increased risk of developing acute leukaemia
Pathogenesis of ALL
Initial primary genetic damage from either
spontaneous mutation, familial defects, drugs
or chemicals, irradiation etc.
Subsequent proliferation with minimal to no
differentiation (or disorderly differentiation)
and maturation results in acute leukaemia
Leukaemic cells accumulate in bone marrow,
suppress normal HSC and normal
haematopoiesis and eventually replace normal
precursor cells by clonal expansion, spill over
into the peripheral blood and infiltrate organs
Manifestation of leukaemia is
mainly due to suppression of normal
haematopoiesis and organ
infiltration
Resultant effect is paucity of normal
red cells, white cells and platelets;
Organ infiltration results in their
enlargement and malfunction
Classificaion of ALL
1. French-American-British (FAB) Classification Based on Morphology
2. WHO Classification Based on Morphology and Cytogenetic features
FAB Classification
FAB sub classified ALL into L1–L3 based on lymphoblast morphology
and immunological markers
L1-small monomorphic lymphoblasts with indistinct nucleoli and scanty
cytoplasm
L2-large, heterogeneous lymphoblasts with more abundant cytoplasm
and prominent nucleoli
L3-large blasts with deeply basophilic & vacuolated abundant cytoplasm
and prominent nucleoli (Burkitt’s type cells)
WHO Classification
Clinical Features of ALL
Signs and symptoms of acute lymphoblastic leukaemia are non –specific
most of the time however, can be related to
Progressive bone marrow infiltration and replacement of normal
haemopoietic cells by leukaemic cells leading to bone marrow failure
Organ/tissue infiltration and spillage of leukaemic cells into peripheral
circulation
Features of bone marrow failure include;
1.Anaemia; weakness, lethargy, light headedness, palpitations.
2.Infections; candidal infections, viral infections like herpes. They typically
present with fever
3.Haemorrhage, petechial rashes, bleeding gums, menorrhagia, rectal
bleed, retina haemorrhages.
4.Neutropenia; fever, malaise, features of mouth, throat, skin, respiratory
perianal or other infections
Features of tissue/organ infiltration include;
1.Splenomegaly, hepatomegaly, lymphadenopathy
2.CNS infiltration causing meningeal syndrom, cranial nerve palsies
3.Bone pains as a result of marrow expansion and cortical bone erosion
4. Leucostasis as a result of spillage of cells into the circulation. Features include, confusion,
retinal haemorrhages, hypoxia
5. Mediastinal involvement particularly in infiltration of the thymus in T-ALL.
Many patients have fever at presentation, which usually resolves after starting
chemotherapy.
Laboratory Investigations
Aims to;
1. Establish the presence of acute leukaemia and distinguish it from other
neoplastic and reactive conditions.
2. Distinguish between AML and ALL
3. Classification of AML or ALL into a specific subtype
4. Therapeutic and prognostic implications/ options.
Laboratory studies in diagnosis of acute leukaemia include;
Full blood count-
•Moderate to severe anaemia,usually normocytic normochromic
•Blood film shows excess blasts irrespective of total WBC count
•Platelets –most often reduced
Bone marrow aspiration cytolology-
• = > 20% blast in the marrow irrespective of the cellularity,
most often blasts are > 90% of all nucleated BM cells
Cytochemistry- Myeloperoxidase, Sudan black, Chloroacetate
esterase, Non-specific esterase, Periodic acid Schiff’s reaction, Acid
phosphatase for classification of AL into AML or ALL –
complements morphological classification
Immunological cell marker analysis (Immunophenotyping).
Gives information about the lineage and stage of development of the particular
cell.
Cell surface antigens named according to the internationally accepted CD (cluster
of differentiation) system are analyzed
Since blood and marrow cells are in fluid suspension, flow cytometric analysis is
the method of choice.
Helps in diagnosis and classification, prognostication, monitoring of therapy
Cytogenetic studies
Confirmation of diagnosis, assessment of prognosis and response to therapy,
assessment of clonality, and detection of minimal residual disease.
Molecular Genetic studies: employs methods like Southern blot analysis,
polymerase chain reaction based techniques and FISH.
Other investigations that may be necessary
include:
Renal function test –U & E, Creatinine, uric
acid
Serum uric acid levels may be elevated
LFT –may reveal extent of disease
involvement
CXR –R/o thymic involvement in T-ALL
(involvement of thymus shows as
mediasternal mass on X -ray)
Diagnosis
Based on the findings in the bone marrow and peripheral blood
The type of leukaemic cells seen determines the type of acute
leukaemia
BM blasts ≥ 20% establishes the diagnosis
Differential diagnosis
Infectious mononucleosis
Myelodysplastic syndrome
NHL infiltrating the marrow
Treatment of Acute Leukaemia
The aim of treatment in AL is to induce complete remission and then to
consolidate this with intensive therapy, hopefully eliminating the disease.
Treatment may be supportive or definitive
Supportive Care
•Blood and blood product transfusion
•Treatment & prophylaxis of infections
•Control and treatment of bleeding complications
•Prevention and or treatment of tumour lysis syndrome
•Psychological support
•Nutritional support
•Antiemetic therapy
•Reproductive issues
Definitive Treatment
•Haemopoietic stem cell transplant-This is aimed at completely
replacing patient’s HSC (BM) with donor SC to take over the process of normal
haematopoiesis. When SCT is successfully done, the patient is cured of the
leukaemia
•Chemotherapy –involves using cytotoxic drugs to induce remission,
consolidate and maintain the remission induced
Remission in AL means, being free of the clinical symptoms and sign of the
disease in question and the return of laboratory parameters to normal
Prognosis
A number of factors affect prognosis following diagnosis.
For ALL, favourable prognostic factor include;
Age; 1- 10 years
Sex ; female
Total Leucocyte Count (TLC): < 50 X 109/L
Immunophenotype; common ALL
CNS disease; Absence of blasts in CSF
Genetic abnormality; Hyperdiploidy
Remission after first induction; early
For ALL, unfavourable prognostic factor include;
Age; <1, >10 years
Sex ; male (testicular relapse)
TLC; > 50 X 109/L
Immunophenotype; T-ALL, Early B- ALL (Smlg+)
CNS disease; Presence of blasts in CSF
Genetic abnormality; Hypodiploidy
Remission after first induction; failure to remit
Conclusion
Acute leukaemias are very fatal
diseases which if not treated,
patient dies in a matter of weeks
from time of diagnosis
SCT is curative in selected patients
References
1.. Essential Haematology by A V Hoffbrand, J E Pettit and P A H Moss.

Weitere ähnliche Inhalte

Ähnlich wie ACUTE LEUKAEMIA Anika.ppt

Childhood acute lympocytic leukemia
Childhood acute lympocytic leukemiaChildhood acute lympocytic leukemia
Childhood acute lympocytic leukemiaVedaste HAKORIMANA
 
Acute leukaemia
Acute leukaemia Acute leukaemia
Acute leukaemia NITISH SHAH
 
Leukemia (blood cancer) presentation
Leukemia (blood cancer) presentationLeukemia (blood cancer) presentation
Leukemia (blood cancer) presentationNehaNupur8
 
Leukocyte disorders.pptx
Leukocyte disorders.pptxLeukocyte disorders.pptx
Leukocyte disorders.pptxDrSamiyahSyeed
 
LEUKEMIA.pptx
LEUKEMIA.pptxLEUKEMIA.pptx
LEUKEMIA.pptxshiwani88
 
LEUKEMIA BY PRIYANKA.pptx...............
LEUKEMIA BY PRIYANKA.pptx...............LEUKEMIA BY PRIYANKA.pptx...............
LEUKEMIA BY PRIYANKA.pptx...............drpriyankaganani
 
Hematological disordres presentation.ppt
Hematological disordres presentation.pptHematological disordres presentation.ppt
Hematological disordres presentation.pptkitati1
 
Leukaemia lecture 01 Acute Myeloid Leukaemia (AML) - Dr. Rabiul Haque
Leukaemia lecture 01   Acute Myeloid Leukaemia (AML) - Dr. Rabiul HaqueLeukaemia lecture 01   Acute Myeloid Leukaemia (AML) - Dr. Rabiul Haque
Leukaemia lecture 01 Acute Myeloid Leukaemia (AML) - Dr. Rabiul HaqueRabiul Haque
 
AML ZANN.pptx
AML ZANN.pptxAML ZANN.pptx
AML ZANN.pptxZannChua1
 
Lukemia in children
Lukemia in children Lukemia in children
Lukemia in children ChinchuBalan
 
An update of Acute leukemia in children.ppt
An update of Acute leukemia in children.pptAn update of Acute leukemia in children.ppt
An update of Acute leukemia in children.pptTareqHasanRana
 
Order a20171110 83
Order a20171110 83Order a20171110 83
Order a20171110 83Thomas Ndalo
 

Ähnlich wie ACUTE LEUKAEMIA Anika.ppt (20)

Leukemia
LeukemiaLeukemia
Leukemia
 
Childhood acute lympocytic leukemia
Childhood acute lympocytic leukemiaChildhood acute lympocytic leukemia
Childhood acute lympocytic leukemia
 
Acute leukaemia
Acute leukaemia Acute leukaemia
Acute leukaemia
 
Leukemia.pptx
Leukemia.pptxLeukemia.pptx
Leukemia.pptx
 
Leukemia (blood cancer) presentation
Leukemia (blood cancer) presentationLeukemia (blood cancer) presentation
Leukemia (blood cancer) presentation
 
Leukocyte disorders.pptx
Leukocyte disorders.pptxLeukocyte disorders.pptx
Leukocyte disorders.pptx
 
LEUKEMIA.pptx
LEUKEMIA.pptxLEUKEMIA.pptx
LEUKEMIA.pptx
 
Leukemia
LeukemiaLeukemia
Leukemia
 
leukemia
leukemialeukemia
leukemia
 
Leukemia english
Leukemia englishLeukemia english
Leukemia english
 
LEUKEMIA BY PRIYANKA.pptx...............
LEUKEMIA BY PRIYANKA.pptx...............LEUKEMIA BY PRIYANKA.pptx...............
LEUKEMIA BY PRIYANKA.pptx...............
 
Hematological disordres presentation.ppt
Hematological disordres presentation.pptHematological disordres presentation.ppt
Hematological disordres presentation.ppt
 
Leukaemia lecture 01 Acute Myeloid Leukaemia (AML) - Dr. Rabiul Haque
Leukaemia lecture 01   Acute Myeloid Leukaemia (AML) - Dr. Rabiul HaqueLeukaemia lecture 01   Acute Myeloid Leukaemia (AML) - Dr. Rabiul Haque
Leukaemia lecture 01 Acute Myeloid Leukaemia (AML) - Dr. Rabiul Haque
 
AML ZANN.pptx
AML ZANN.pptxAML ZANN.pptx
AML ZANN.pptx
 
Lukemia in children
Lukemia in children Lukemia in children
Lukemia in children
 
leukemias.ppt
leukemias.pptleukemias.ppt
leukemias.ppt
 
An update of Acute leukemia in children.ppt
An update of Acute leukemia in children.pptAn update of Acute leukemia in children.ppt
An update of Acute leukemia in children.ppt
 
LEUKEMIA.pptx
LEUKEMIA.pptxLEUKEMIA.pptx
LEUKEMIA.pptx
 
ACUTE LEUKEMIA
ACUTE LEUKEMIAACUTE LEUKEMIA
ACUTE LEUKEMIA
 
Order a20171110 83
Order a20171110 83Order a20171110 83
Order a20171110 83
 

Kürzlich hochgeladen

call girls in green park DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in green park  DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️call girls in green park  DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in green park DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️saminamagar
 
world health day presentation ppt download
world health day presentation ppt downloadworld health day presentation ppt download
world health day presentation ppt downloadAnkitKumar311566
 
Music Therapy's Impact in Palliative Care| IAPCON2024| Dr. Tara Rajendran
Music Therapy's Impact in Palliative Care| IAPCON2024| Dr. Tara RajendranMusic Therapy's Impact in Palliative Care| IAPCON2024| Dr. Tara Rajendran
Music Therapy's Impact in Palliative Care| IAPCON2024| Dr. Tara RajendranTara Rajendran
 
Biomechanics- Shoulder Joint!!!!!!!!!!!!
Biomechanics- Shoulder Joint!!!!!!!!!!!!Biomechanics- Shoulder Joint!!!!!!!!!!!!
Biomechanics- Shoulder Joint!!!!!!!!!!!!ibtesaam huma
 
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATRO
April 2024 ONCOLOGY CARTOON by  DR KANHU CHARAN PATROApril 2024 ONCOLOGY CARTOON by  DR KANHU CHARAN PATRO
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATROKanhu Charan
 
Glomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and  determinants of glomerular filtration .pptxGlomerular Filtration and  determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptxDr.Nusrat Tariq
 
call girls in aerocity DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in aerocity DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️call girls in aerocity DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in aerocity DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️saminamagar
 
COVID-19 (NOVEL CORONA VIRUS DISEASE PANDEMIC ).pptx
COVID-19  (NOVEL CORONA  VIRUS DISEASE PANDEMIC ).pptxCOVID-19  (NOVEL CORONA  VIRUS DISEASE PANDEMIC ).pptx
COVID-19 (NOVEL CORONA VIRUS DISEASE PANDEMIC ).pptxBibekananda shah
 
Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)Mohamed Rizk Khodair
 
The next social challenge to public health: the information environment.pptx
The next social challenge to public health:  the information environment.pptxThe next social challenge to public health:  the information environment.pptx
The next social challenge to public health: the information environment.pptxTina Purnat
 
PULMONARY EMBOLISM AND ITS MANAGEMENTS.pdf
PULMONARY EMBOLISM AND ITS MANAGEMENTS.pdfPULMONARY EMBOLISM AND ITS MANAGEMENTS.pdf
PULMONARY EMBOLISM AND ITS MANAGEMENTS.pdfDolisha Warbi
 
Presentation on General Anesthetics pdf.
Presentation on General Anesthetics pdf.Presentation on General Anesthetics pdf.
Presentation on General Anesthetics pdf.Prerana Jadhav
 
SYNDESMOTIC INJURY- ANATOMICAL REPAIR.pptx
SYNDESMOTIC INJURY- ANATOMICAL REPAIR.pptxSYNDESMOTIC INJURY- ANATOMICAL REPAIR.pptx
SYNDESMOTIC INJURY- ANATOMICAL REPAIR.pptxdrashraf369
 
Case Report Peripartum Cardiomyopathy.pptx
Case Report Peripartum Cardiomyopathy.pptxCase Report Peripartum Cardiomyopathy.pptx
Case Report Peripartum Cardiomyopathy.pptxNiranjan Chavan
 
Radiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptxRadiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptxDr. Dheeraj Kumar
 
Big Data Analysis Suggests COVID Vaccination Increases Excess Mortality Of ...
Big Data Analysis Suggests COVID  Vaccination Increases Excess Mortality Of  ...Big Data Analysis Suggests COVID  Vaccination Increases Excess Mortality Of  ...
Big Data Analysis Suggests COVID Vaccination Increases Excess Mortality Of ...sdateam0
 
Culture and Health Disorders Social change.pptx
Culture and Health Disorders Social change.pptxCulture and Health Disorders Social change.pptx
Culture and Health Disorders Social change.pptxDr. Dheeraj Kumar
 
POST NATAL EXERCISES AND ITS IMPACT.pptx
POST NATAL EXERCISES AND ITS IMPACT.pptxPOST NATAL EXERCISES AND ITS IMPACT.pptx
POST NATAL EXERCISES AND ITS IMPACT.pptxvirengeeta
 
History and Development of Pharmacovigilence.pdf
History and Development of Pharmacovigilence.pdfHistory and Development of Pharmacovigilence.pdf
History and Development of Pharmacovigilence.pdfSasikiranMarri
 
Hematology and Immunology - Leukocytes Functions
Hematology and Immunology - Leukocytes FunctionsHematology and Immunology - Leukocytes Functions
Hematology and Immunology - Leukocytes FunctionsMedicoseAcademics
 

Kürzlich hochgeladen (20)

call girls in green park DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in green park  DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️call girls in green park  DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in green park DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
 
world health day presentation ppt download
world health day presentation ppt downloadworld health day presentation ppt download
world health day presentation ppt download
 
Music Therapy's Impact in Palliative Care| IAPCON2024| Dr. Tara Rajendran
Music Therapy's Impact in Palliative Care| IAPCON2024| Dr. Tara RajendranMusic Therapy's Impact in Palliative Care| IAPCON2024| Dr. Tara Rajendran
Music Therapy's Impact in Palliative Care| IAPCON2024| Dr. Tara Rajendran
 
Biomechanics- Shoulder Joint!!!!!!!!!!!!
Biomechanics- Shoulder Joint!!!!!!!!!!!!Biomechanics- Shoulder Joint!!!!!!!!!!!!
Biomechanics- Shoulder Joint!!!!!!!!!!!!
 
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATRO
April 2024 ONCOLOGY CARTOON by  DR KANHU CHARAN PATROApril 2024 ONCOLOGY CARTOON by  DR KANHU CHARAN PATRO
April 2024 ONCOLOGY CARTOON by DR KANHU CHARAN PATRO
 
Glomerular Filtration and determinants of glomerular filtration .pptx
Glomerular Filtration and  determinants of glomerular filtration .pptxGlomerular Filtration and  determinants of glomerular filtration .pptx
Glomerular Filtration and determinants of glomerular filtration .pptx
 
call girls in aerocity DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in aerocity DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️call girls in aerocity DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
call girls in aerocity DELHI 🔝 >༒9540349809 🔝 genuine Escort Service 🔝✔️✔️
 
COVID-19 (NOVEL CORONA VIRUS DISEASE PANDEMIC ).pptx
COVID-19  (NOVEL CORONA  VIRUS DISEASE PANDEMIC ).pptxCOVID-19  (NOVEL CORONA  VIRUS DISEASE PANDEMIC ).pptx
COVID-19 (NOVEL CORONA VIRUS DISEASE PANDEMIC ).pptx
 
Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)Primary headache and facial pain. (2024)
Primary headache and facial pain. (2024)
 
The next social challenge to public health: the information environment.pptx
The next social challenge to public health:  the information environment.pptxThe next social challenge to public health:  the information environment.pptx
The next social challenge to public health: the information environment.pptx
 
PULMONARY EMBOLISM AND ITS MANAGEMENTS.pdf
PULMONARY EMBOLISM AND ITS MANAGEMENTS.pdfPULMONARY EMBOLISM AND ITS MANAGEMENTS.pdf
PULMONARY EMBOLISM AND ITS MANAGEMENTS.pdf
 
Presentation on General Anesthetics pdf.
Presentation on General Anesthetics pdf.Presentation on General Anesthetics pdf.
Presentation on General Anesthetics pdf.
 
SYNDESMOTIC INJURY- ANATOMICAL REPAIR.pptx
SYNDESMOTIC INJURY- ANATOMICAL REPAIR.pptxSYNDESMOTIC INJURY- ANATOMICAL REPAIR.pptx
SYNDESMOTIC INJURY- ANATOMICAL REPAIR.pptx
 
Case Report Peripartum Cardiomyopathy.pptx
Case Report Peripartum Cardiomyopathy.pptxCase Report Peripartum Cardiomyopathy.pptx
Case Report Peripartum Cardiomyopathy.pptx
 
Radiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptxRadiation Dosimetry Parameters and Isodose Curves.pptx
Radiation Dosimetry Parameters and Isodose Curves.pptx
 
Big Data Analysis Suggests COVID Vaccination Increases Excess Mortality Of ...
Big Data Analysis Suggests COVID  Vaccination Increases Excess Mortality Of  ...Big Data Analysis Suggests COVID  Vaccination Increases Excess Mortality Of  ...
Big Data Analysis Suggests COVID Vaccination Increases Excess Mortality Of ...
 
Culture and Health Disorders Social change.pptx
Culture and Health Disorders Social change.pptxCulture and Health Disorders Social change.pptx
Culture and Health Disorders Social change.pptx
 
POST NATAL EXERCISES AND ITS IMPACT.pptx
POST NATAL EXERCISES AND ITS IMPACT.pptxPOST NATAL EXERCISES AND ITS IMPACT.pptx
POST NATAL EXERCISES AND ITS IMPACT.pptx
 
History and Development of Pharmacovigilence.pdf
History and Development of Pharmacovigilence.pdfHistory and Development of Pharmacovigilence.pdf
History and Development of Pharmacovigilence.pdf
 
Hematology and Immunology - Leukocytes Functions
Hematology and Immunology - Leukocytes FunctionsHematology and Immunology - Leukocytes Functions
Hematology and Immunology - Leukocytes Functions
 

ACUTE LEUKAEMIA Anika.ppt

  • 3. INTRODUCTION Leukaemias are a group of disorders characterized by the accumulation of malignant white cells in the bone marrow and blood. These abnormal cells cause symptoms because of (i) bone marrow failure (e.g. anaemia, neutropenia, thrombocytopenia); and (ii) infiltration of organs (e.g. liver, spleen, lymph nodes, meninges, brain, skin or testes).
  • 4. Definition Leukaemias are malignant neoplasms of the haemopoietic stem cell characterized by excessive clonal proliferation and diffuse replacement of the bone marrow by the neoplastic cells with spilling over into the peripheral blood and organ infiltration. They are classified broadly into; 1. Acute Leukaemias 2. Chronic Leukaemias
  • 5. Acute Leukaemias Acute Leukaemias are malignant clonal disorders originating in haematopoietic stem cells or its committed progenitors characterized by the proliferation of poorly differentiated blast (immature) cells in the bone marrow and subsequent spillage into the peripheral blood and tissues. Acute leukaemias are usually aggressive diseases and are normally defined by the presence of over 20% of blast cells in the blood or bone marrow at clinical presentation. Acute Leukaemias are further subdivided into i. Acute myeloblastic leukaemia (AML) and ii. Acute lymphoblastic leukaemia (ALL).
  • 6. AML is a malignant neoplasm of haematopoietic stem cells originating in bone marrow and characterised by proliferation of blast cells of myeloid lineage. ALL is a malignant neoplasm of haematopoietic stem cells of lymphoid lineage arising from the bone marrow.
  • 7. Epidemiology ALL is the most common haematologic malignancy of childhood.  Highest at 3- 7 years with 75% of cases occurring before the age of 6 with a secondary rise after the age of 40. Males are frequently more affected than females.
  • 8. Aetiology of ALL Unknown Various factors associated with increased risk of acute leukaemias include: i) Genetic factors Inherited susceptibility Association with congenital or hereditary syndromes-e.gDown’s syndrome (20 times increased incidence),Bloom’s syndrome,Fanconi’s syndrome,Klinfelter’s syndrome,Ataxia telangiectasia,Osteogenesis imperfect,Wiskott-Aldrich syndrome,Diamond- Blackfan syndrome,Kostmann’s syndrome etc
  • 9. ii). Acquired conditions include; Aplastic anaemia Myelodysplastic syndrome (MDS) Paroxysmal nocturnal haemoglobinuria (PNH) Myeloproliferative neoplasms (MPN) iii). Environmental factors include; Chemicals – chronic exposure to benzene. Radiation – radiation to the marrow is leukaemogenic. Also , paternal irradiation has been identified as a risk factor. Radiation may be natural UV light, diagnostic or therapeutic Viral infections – HTLV causing ATLL, EBV causing Burkitt’s lymphoma/Leukemia Drugs – Alkylating agents e.g. Chlorambucil, Melphalan, Etoposide Infections – children with less exposure to infection particularly of a high social class have increased risk of developing acute leukaemia
  • 10. Pathogenesis of ALL Initial primary genetic damage from either spontaneous mutation, familial defects, drugs or chemicals, irradiation etc. Subsequent proliferation with minimal to no differentiation (or disorderly differentiation) and maturation results in acute leukaemia Leukaemic cells accumulate in bone marrow, suppress normal HSC and normal haematopoiesis and eventually replace normal precursor cells by clonal expansion, spill over into the peripheral blood and infiltrate organs
  • 11. Manifestation of leukaemia is mainly due to suppression of normal haematopoiesis and organ infiltration Resultant effect is paucity of normal red cells, white cells and platelets; Organ infiltration results in their enlargement and malfunction
  • 12. Classificaion of ALL 1. French-American-British (FAB) Classification Based on Morphology 2. WHO Classification Based on Morphology and Cytogenetic features
  • 13. FAB Classification FAB sub classified ALL into L1–L3 based on lymphoblast morphology and immunological markers L1-small monomorphic lymphoblasts with indistinct nucleoli and scanty cytoplasm L2-large, heterogeneous lymphoblasts with more abundant cytoplasm and prominent nucleoli L3-large blasts with deeply basophilic & vacuolated abundant cytoplasm and prominent nucleoli (Burkitt’s type cells)
  • 15. Clinical Features of ALL Signs and symptoms of acute lymphoblastic leukaemia are non –specific most of the time however, can be related to Progressive bone marrow infiltration and replacement of normal haemopoietic cells by leukaemic cells leading to bone marrow failure Organ/tissue infiltration and spillage of leukaemic cells into peripheral circulation
  • 16. Features of bone marrow failure include; 1.Anaemia; weakness, lethargy, light headedness, palpitations. 2.Infections; candidal infections, viral infections like herpes. They typically present with fever 3.Haemorrhage, petechial rashes, bleeding gums, menorrhagia, rectal bleed, retina haemorrhages. 4.Neutropenia; fever, malaise, features of mouth, throat, skin, respiratory perianal or other infections
  • 17. Features of tissue/organ infiltration include; 1.Splenomegaly, hepatomegaly, lymphadenopathy 2.CNS infiltration causing meningeal syndrom, cranial nerve palsies 3.Bone pains as a result of marrow expansion and cortical bone erosion 4. Leucostasis as a result of spillage of cells into the circulation. Features include, confusion, retinal haemorrhages, hypoxia 5. Mediastinal involvement particularly in infiltration of the thymus in T-ALL. Many patients have fever at presentation, which usually resolves after starting chemotherapy.
  • 18. Laboratory Investigations Aims to; 1. Establish the presence of acute leukaemia and distinguish it from other neoplastic and reactive conditions. 2. Distinguish between AML and ALL 3. Classification of AML or ALL into a specific subtype 4. Therapeutic and prognostic implications/ options.
  • 19. Laboratory studies in diagnosis of acute leukaemia include; Full blood count- •Moderate to severe anaemia,usually normocytic normochromic •Blood film shows excess blasts irrespective of total WBC count •Platelets –most often reduced Bone marrow aspiration cytolology- • = > 20% blast in the marrow irrespective of the cellularity, most often blasts are > 90% of all nucleated BM cells Cytochemistry- Myeloperoxidase, Sudan black, Chloroacetate esterase, Non-specific esterase, Periodic acid Schiff’s reaction, Acid phosphatase for classification of AL into AML or ALL – complements morphological classification
  • 20. Immunological cell marker analysis (Immunophenotyping). Gives information about the lineage and stage of development of the particular cell. Cell surface antigens named according to the internationally accepted CD (cluster of differentiation) system are analyzed Since blood and marrow cells are in fluid suspension, flow cytometric analysis is the method of choice. Helps in diagnosis and classification, prognostication, monitoring of therapy Cytogenetic studies Confirmation of diagnosis, assessment of prognosis and response to therapy, assessment of clonality, and detection of minimal residual disease. Molecular Genetic studies: employs methods like Southern blot analysis, polymerase chain reaction based techniques and FISH.
  • 21. Other investigations that may be necessary include: Renal function test –U & E, Creatinine, uric acid Serum uric acid levels may be elevated LFT –may reveal extent of disease involvement CXR –R/o thymic involvement in T-ALL (involvement of thymus shows as mediasternal mass on X -ray)
  • 22. Diagnosis Based on the findings in the bone marrow and peripheral blood The type of leukaemic cells seen determines the type of acute leukaemia BM blasts ≥ 20% establishes the diagnosis
  • 24. Treatment of Acute Leukaemia The aim of treatment in AL is to induce complete remission and then to consolidate this with intensive therapy, hopefully eliminating the disease. Treatment may be supportive or definitive Supportive Care •Blood and blood product transfusion •Treatment & prophylaxis of infections •Control and treatment of bleeding complications •Prevention and or treatment of tumour lysis syndrome •Psychological support •Nutritional support •Antiemetic therapy •Reproductive issues
  • 25. Definitive Treatment •Haemopoietic stem cell transplant-This is aimed at completely replacing patient’s HSC (BM) with donor SC to take over the process of normal haematopoiesis. When SCT is successfully done, the patient is cured of the leukaemia •Chemotherapy –involves using cytotoxic drugs to induce remission, consolidate and maintain the remission induced Remission in AL means, being free of the clinical symptoms and sign of the disease in question and the return of laboratory parameters to normal
  • 26. Prognosis A number of factors affect prognosis following diagnosis. For ALL, favourable prognostic factor include; Age; 1- 10 years Sex ; female Total Leucocyte Count (TLC): < 50 X 109/L Immunophenotype; common ALL CNS disease; Absence of blasts in CSF Genetic abnormality; Hyperdiploidy Remission after first induction; early
  • 27. For ALL, unfavourable prognostic factor include; Age; <1, >10 years Sex ; male (testicular relapse) TLC; > 50 X 109/L Immunophenotype; T-ALL, Early B- ALL (Smlg+) CNS disease; Presence of blasts in CSF Genetic abnormality; Hypodiploidy Remission after first induction; failure to remit
  • 28. Conclusion Acute leukaemias are very fatal diseases which if not treated, patient dies in a matter of weeks from time of diagnosis SCT is curative in selected patients
  • 29. References 1.. Essential Haematology by A V Hoffbrand, J E Pettit and P A H Moss.