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Leukemia
Dr. Deepak K. Gupta
Introduction
• Neoplastic proliferations of white blood cells—
leukaemias.
• Incidence is higher in men than in women
• Cl...
Introduction
www.facebook.com/notesdental
Classification
www.facebook.com/notesdental
Etiology
• Heredity
• Infections: Human T cell leukaemia-lymphoma
virus I (HTLV-I)
• Environmental factors
– Ionising radi...
www.facebook.com/notesdental
ACUTE MYELOID LEUKAEMIA
• heterogeneous disease characterised by
infiltration of malignant myeloid cells into
the blood, b...
Classification
• French-American-British (FAB) CLASSIFICATION
– Based on morphology and cytochemistry,
– It divides AML in...
FAB CLASSIFICATION
www.facebook.com/notesdental
WHO CLASSIFICATION (2002)
• AML with recurrent cytogenetic abnormalities
• AML with multilineage dysplasia
• AML and MDS (...
Clinical Features
• AML and ALL share many common clinical
features - difficult to distinguish on clinical
features alone....
Clinical Features: Bone marrow failure
• Anaemia producing pallor, lethargy, dyspnoea.
• Bleeding manifestations due to
th...
Clinical Features: Organ infiltration
• due to replacement of the marrow and other
tissues by leukaemic cells.
• Pain and ...
Clinical Features: Organ infiltration
• Gum hypertrophy due to leukaemic infiltration of the
gingivae is a frequent findin...
Clinical Features: Organ infiltration
www.facebook.com/notesdental
Laboratory Findings
• The diagnosis of AML is made by a combination of routine
blood picture and bone marrow examination, ...
Laboratory Findings
www.facebook.com/notesdental
Laboratory Findings
www.facebook.com/notesdental
Laboratory Findings: BONE MARROW
EXAMINATION
• Cellularity: Typically, the marrow is hypercellular but
sometimes a ‘blood ...
Laboratory Findings: BONE MARROW
EXAMINATION
www.facebook.com/notesdental
Laboratory Findings
• CYTOCHEMISTRY: Commonly employed cytochemical
stains, as an aid to classify the type of
– Myeloperox...
Treatment and Complications
• TREATMENT OF ANAEMIA AND HAEMORRHAGE.
– Anaemia and haemorrhage are managed by fresh
blood t...
Treatment and Complications
• CYTOTOXIC DRUG THERAPY
– Aim: firstly induce remission, secondly to continue
therapy to redu...
Treatment and Complications
• BONE MARROW TRANSPLANTATION
– Bone marrow (or stem cell) transplantation from
suitable allog...
Prognosis
• Remission rate with AML is lower (50-70%) than in
ALL,
• Often takes longer to achieve remission, and disease-...
Acute Lymphocytic Leukemia (ALL)
• Most common type of leukemia in children
• 15% of acute leukemia in adults
• Immature l...
Chronic Myeloid Leukemia (CML)
www.facebook.com/notesdental
Introduction
• Excessive development of mature neoplastic
granulocytes in the bone marrow
– Move into the peripheral blood...
Clinical Features
• 20% of all leukaemias
• Peak incidence is seen in 3rd and 4th decades of
life.
• A distinctive variant...
Clinical Features
• Splenomegaly is almost always present and is
frequently massive.
• Bleeding tendencies such as easy br...
Laboratory Findings
• The diagnosis of CML is generally possible on
blood picture alone. However, bone marrow,
cytochemica...
www.facebook.com/notesdental
Laboratory Findings
– White blood cells. Characteristically, there is marked
leucocytosis (approximately 200,000/μl or mor...
Laboratory Findings
www.facebook.com/notesdental
Laboratory Findings
• BONE MARROW EXAMINATION
• Cellularity: hypercellularity with total or partial replacement of
fat spa...
Philadelphia (Ph) chromosome
www.facebook.com/notesdental
Laboratory Findings
• CYTOCHEMISTRY
• The only significant finding on cytochemical stains is
reduced scores of neutrophil ...
Treatment
• Knowledge of molecular mechanism of CML has brought
about major changes in its therapy.
• The approach of mode...
Chronic Lymphocytic Leukemia (CLL)
• Production and accumulation of functionally
inactive but long-lived, mature-appearing...
References
• Robbinson's basic pathology 8 ed
• Harsh Mohan - Textbook of Pathology 6th Ed.
• Color atlas of pathology
www...
THANKS……
Like, share and comment on
https://www.facebook.com/notesdental
http://www.slideshare.net/DeepakKumarGupta2
www.f...
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Leukemia

Leukemia

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Leukemia

  1. 1. Leukemia Dr. Deepak K. Gupta
  2. 2. Introduction • Neoplastic proliferations of white blood cells— leukaemias. • Incidence is higher in men than in women • Classified on the basis of cell types predominantly involved – myeloid or lymphoid • Acute: predominance of undifferentiated leucocyte precursors or leukaemic blasts – Acute myeloblastic leukaemia (AML) - at all ages – Acute lymphoblastic leukaemia (ALL) – primarily a disease of children and young adults • Chronic: late precursor series of leucocytes – Chronic myeloid leukaemia (CML) – middle age – Chronic lymphocytic leukaemias (CLL) - elderly www.facebook.com/notesdental
  3. 3. Introduction www.facebook.com/notesdental
  4. 4. Classification www.facebook.com/notesdental
  5. 5. Etiology • Heredity • Infections: Human T cell leukaemia-lymphoma virus I (HTLV-I) • Environmental factors – Ionising radiation – Chemical carcinogens – Certain drugs. • Association with diseases of immunity: Immunodeficiency diseases like AIDS and iatrogenic immunosuppression induced by chemotherapy or radiation, www.facebook.com/notesdental
  6. 6. www.facebook.com/notesdental
  7. 7. ACUTE MYELOID LEUKAEMIA • heterogeneous disease characterised by infiltration of malignant myeloid cells into the blood, bone marrow and other tissues • mainly a disease of adults (median age 50 years) • develops due to inhibition of maturation of myeloid stem cells due to mutations - induced by several etiologic factors www.facebook.com/notesdental
  8. 8. Classification • French-American-British (FAB) CLASSIFICATION – Based on morphology and cytochemistry, – It divides AML into 8 subtypes (M0 to M7) • WHO CLASSIFICATION (2002) – differs from revised FAB classification – limited reliance on cytochemistry for making the diagnosis of subtype of AML – Based on clinical, cytogenetic and molecular abnormalitie www.facebook.com/notesdental
  9. 9. FAB CLASSIFICATION www.facebook.com/notesdental
  10. 10. WHO CLASSIFICATION (2002) • AML with recurrent cytogenetic abnormalities • AML with multilineage dysplasia • AML and MDS (Myelodysplastic Syndrome), therapy-related • AML, not otherwise categorised www.facebook.com/notesdental
  11. 11. Clinical Features • AML and ALL share many common clinical features - difficult to distinguish on clinical features alone. • 25% of patients with AML: preleukaemic syndrome with anaemia may be present for a few months to years prior to the development of overt leukaemia. • Clinical manifestations of AML are divided into 2 groups due to – Bone marrow failure – Organ infiltration www.facebook.com/notesdental
  12. 12. Clinical Features: Bone marrow failure • Anaemia producing pallor, lethargy, dyspnoea. • Bleeding manifestations due to thrombocytopenia causing spontaneous bruises, petechiae, bleeding from gums and other bleeding tendencies. • Infections are quite common and include those of mouth, throat, skin, respiratory, perianal and other sites. • Fever : no obvious source of infection can be found and may occur in the absence of infection. www.facebook.com/notesdental
  13. 13. Clinical Features: Organ infiltration • due to replacement of the marrow and other tissues by leukaemic cells. • Pain and tenderness of bones (e.g. sternal tenderness) - bone infarcts or subperiosteal infiltrates by leukaemic cells. • Lymphadenopathy and enlargement of the tonsils may occur • Splenomegaly of moderate grade may occur – Splenic infarction, subcapsular haemorrhages, and rarely, splenic rupture may occur. • Hepatomegaly www.facebook.com/notesdental
  14. 14. Clinical Features: Organ infiltration • Gum hypertrophy due to leukaemic infiltration of the gingivae is a frequent finding. • Chloroma or granulocytic sarcoma : localised tumour forming mass occurring in the skin or orbit - greenish in appearance due to the presence of myeloperoxidase. • Meningeal involvement manifested by raised intracranial pressure, headache, nausea and vomiting, blurring of vision and diplopia – Sudden death from massive intracranial haemorrhage as a result of leucostasis may occur. – Other organ infiltrations include testicular swelling and mediastinal compression www.facebook.com/notesdental
  15. 15. Clinical Features: Organ infiltration www.facebook.com/notesdental
  16. 16. Laboratory Findings • The diagnosis of AML is made by a combination of routine blood picture and bone marrow examination, coupled with cytochemical stains and other special laboratory investigations. • BLOOD PICTURE. – Anaemia. – Thrombocytopenia: moderately to severely reduced (below 50,000/μl) but occasionally it may be normal. – White blood cells: ranges from subnormal-to-markedly elevated values • 25% of patients – reduced to 1,000-4,000 /μl. • More often, however, there is progressive rise in white cell count which may exceed 100,000/μl in more advanced disease. • Majority of leucocytes in the peripheral blood are blasts and there is often neutropenia due to marrow infiltration by leukaemic cells. www.facebook.com/notesdental
  17. 17. Laboratory Findings www.facebook.com/notesdental
  18. 18. Laboratory Findings www.facebook.com/notesdental
  19. 19. Laboratory Findings: BONE MARROW EXAMINATION • Cellularity: Typically, the marrow is hypercellular but sometimes a ‘blood tap’ or ‘dry tap’ occurs. • Leukaemic cells – generally tightly packed with leukaemic blast cells – Romanowsky stains: cytochemical stains may be employed to know the type of leukaemia. Erythropoiesis. • Erythropoietic cells are reduced. • Megakaryocytes. They are usually reduced or absent. • Cytogenetics: shows karyotypic abnormalities in 75% of cases which may have a relationship to prognosis. • Immunophenotyping. AML cells express CD13 and CD33 antigens. M7 shows CD41 and CD42 positivity. www.facebook.com/notesdental
  20. 20. Laboratory Findings: BONE MARROW EXAMINATION www.facebook.com/notesdental
  21. 21. Laboratory Findings • CYTOCHEMISTRY: Commonly employed cytochemical stains, as an aid to classify the type of – Myeloperoxidase: Positive in immature myeloid cells containing granules and Auer rods – Sudan Black – Periodic acid-Schiff (PAS): Positive in immature lymphoid cells and in erythroleukaemia (M6) – Non-specific esterase (NSE): Positive in monocytic series (M4 and M5). – Acid phosphatase: Focal positivity in leukaemic blasts in ALL and diffuse reaction in monocytic cells (M4 and M5). • BIOCHEMICAL INVESTIGATIONS: may be of some help – Serum muramidase: elevated in myelomonocytic (M4) and monocytic (M5) leukaemias. – Serum uric acid: frequently increased www.facebook.com/notesdental
  22. 22. Treatment and Complications • TREATMENT OF ANAEMIA AND HAEMORRHAGE. – Anaemia and haemorrhage are managed by fresh blood transfusions and platelet concentrates. – Patients with severe thrombocytopenia (platelet count below 20,000/μl) require regular platelet transfusions • haemorrhage is an important cause of death in these cases • TREATMENT AND PROPHYLAXIS OF INFECTION www.facebook.com/notesdental
  23. 23. Treatment and Complications • CYTOTOXIC DRUG THERAPY – Aim: firstly induce remission, secondly to continue therapy to reduce the hidden leukaemic cell population by repeated courses of therapy. – The most effective treatment of AML is a combination of 3 drugs: cytosine arabinoside, anthracyclines (daunorubicin, adriamycin) and 6-thioguanine. – Another addition is amsacrine (m-AMSA) administered with cytosine arabinoside, with or without 6-thioguanine. www.facebook.com/notesdental
  24. 24. Treatment and Complications • BONE MARROW TRANSPLANTATION – Bone marrow (or stem cell) transplantation from suitable allogenic or autologous donor – The basic principle of marrow transplantation is to reconstitute the patient’s haematopoietic system after total body irradiation and intensive chemotherapy – kill the remaining leukemic cell – Bone marrow transplantation has resulted in cure in about half the cases. www.facebook.com/notesdental
  25. 25. Prognosis • Remission rate with AML is lower (50-70%) than in ALL, • Often takes longer to achieve remission, and disease- free intervals are shorter. • AML is most malignant of all leukaemia • Survival with treatment is 12-18 months. www.facebook.com/notesdental
  26. 26. Acute Lymphocytic Leukemia (ALL) • Most common type of leukemia in children • 15% of acute leukemia in adults • Immature lymphocytes proliferate in the bone marrow • Signs and symptoms may appear abruptly – Fever, bleeding • Insidious with progressive – Weakness, fatigue • Central nervous system manifestations www.facebook.com/notesdental
  27. 27. Chronic Myeloid Leukemia (CML) www.facebook.com/notesdental
  28. 28. Introduction • Excessive development of mature neoplastic granulocytes in the bone marrow – Move into the peripheral blood in massive numbers – Ultimately infiltrate the liver and spleen • Philadelphia chromosome – The chromosome abnormality that causes chronic myeloid leukemia (CML) (9 &22) – Genetic marker • Chronic, stable phase followed by acute, aggressive (blastic) phase www.facebook.com/notesdental
  29. 29. Clinical Features • 20% of all leukaemias • Peak incidence is seen in 3rd and 4th decades of life. • A distinctive variant seen in children is called juvenile CML. • Both sexes are affected equally. • Some of the common presenting manifestations are as under – Anemia – Hypermetabolism such as weight loss, lassitude, anorexia, night sweats. www.facebook.com/notesdental
  30. 30. Clinical Features • Splenomegaly is almost always present and is frequently massive. • Bleeding tendencies such as easy bruising, epistaxis, menorrhagia and haematomas may occur. • Less common features include gout, visual disturbance, neurologic manifestations. • Juvenile CML – often associated with lymph node enlargement than splenomegaly. – Other features are frequent infections, haemorrhagic manifestations and facial rash. www.facebook.com/notesdental
  31. 31. Laboratory Findings • The diagnosis of CML is generally possible on blood picture alone. However, bone marrow, cytochemical stains and other investigations are also useful • BLOOD PICTURE – Anaemia. Anaemia is usually of moderate degree and is normocytic normochromic in type. www.facebook.com/notesdental
  32. 32. www.facebook.com/notesdental
  33. 33. Laboratory Findings – White blood cells. Characteristically, there is marked leucocytosis (approximately 200,000/μl or more at the time of presentation). The natural history of CML consists of 3 phases—chronic, accelerated, and blastic. • Chronic phase: begins as a myeloproliferative disorder and consists of excessive proliferation of myeloid cells of intermediate grade (i.e. myelocytes and metamyelocytes) and mature segmented neutrophils. • Accelerated phase: increasing degree of anaemia, blast count in blood or marrow between 10-20%, marrow basophils 20% or more, and platelet count falling below 1,00,000/μl. • Blastic phase or blast crisis: blood or marrow blasts >20%. Myeloid blast crisis in CML is more common and resembles AML. – Auer rods are not seen in myeloblasts of CML in blast crisis. – Platelets. Platelet count may be normal but is raised in about half the cases. www.facebook.com/notesdental
  34. 34. Laboratory Findings www.facebook.com/notesdental
  35. 35. Laboratory Findings • BONE MARROW EXAMINATION • Cellularity: hypercellularity with total or partial replacement of fat spaces by proliferating myeloid cells. • Myeloid cells: predominate in the bone marrow with increased myeloid-erythroid ratio. The differential counts of myeloid cells in the marrow show similar findings as seen in the peripheral blood with predominance of myelocytes. • Erythropoiesis: normoblastic but there is reduction in erythropoietic cells. • Megakaryocytes: are conspicuous but lare usually smaller in size than normal. • Cytogenetics: the characteristic chromosomal abnormality called Philadelphia (Ph) chromosome (90-95%) www.facebook.com/notesdental
  36. 36. Philadelphia (Ph) chromosome www.facebook.com/notesdental
  37. 37. Laboratory Findings • CYTOCHEMISTRY • The only significant finding on cytochemical stains is reduced scores of neutrophil alkaline phosphatase (NAP) • These helps to distinguish CML from myeloid leukaemoid reaction in which case NAP scores are elevated • OTHER INVESTIGATIONS • Elevated serum vitamin B 12 and vitamin B12 binding capacity. • Elevated serum uric acid (hyperuricaemia). www.facebook.com/notesdental
  38. 38. Treatment • Knowledge of molecular mechanism of CML has brought about major changes in its therapy. • The approach of modern therapy in CML is targetted at removal of all malignant clones of cells bearing BCR/ABL fusion protein, • So that patient reverts back to prolonged non-clonal haematopoiesis. • This is achievable by the following approaches – Imatinib oral therapy – Allogenic bone marrow (stem cell) transplantation. – Interferon-α. – Chemotherapy – Others: splenic irradiation, splenectomy and leucopheresis. • The most common cause of death (in 80% cases) in CML is disease acceleration and blastic transformation www.facebook.com/notesdental
  39. 39. Chronic Lymphocytic Leukemia (CLL) • Production and accumulation of functionally inactive but long-lived, mature-appearing lymphocytes • B cell involvement • Lymph node enlargement is noticeable throughout the body – ↑ incidence of infection • Complications from early-stage CLL is rare – May develop as the disease advances – Pain, paralysis from enlarged lymph nodes causing pressure www.facebook.com/notesdental
  40. 40. References • Robbinson's basic pathology 8 ed • Harsh Mohan - Textbook of Pathology 6th Ed. • Color atlas of pathology www.facebook.com/notesdental
  41. 41. THANKS…… Like, share and comment on https://www.facebook.com/notesdental http://www.slideshare.net/DeepakKumarGupta2 www.facebook.com/notesdental

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