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Acute Leukemia Kristine Krafts, M.D..

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1 Acute Leukemia Kristine Krafts, M.D.

2

3 Hematologic Malignancies
Leukemia Malignancy of hematopoietic cells Starts in bone marrow, can spread to blood, nodes Myeloid or lymphoid Acute or chronic Lymphoma Starts in lymph nodes, can spread to blood, marrow Lymphoid only Hodgkin or non-Hodgkin

4 Hematologic Malignancies
Leukemias Acute leukemias Chronic leukemias Lymphomas Hodgkin lymphoma Non-Hodgkin lymphoma Plasma cell disorders Multiple myeloma

5

6 Hematologic Malignancies
Myeloid Lymphoid Acute myeloid leukemia Chronic myeloid leukemia Acute lymphoblastic leukemia Chronic lymphocytic leukemia Hodgkin lymphoma Non-Hodgkin lymphoma Multiple myeloma

7 How is a diagnosis made? Clinical setting Morphology Immunophenotyping
Molecular studies Cytogenetics

8

9 Bone marrow biopsy needle

10 Bone marrow biopsy: cellularity

11 Normal bone marrow biopsy

12 Normal bone marrow biopsy

13 Bone marrow aspiration needle

14 Bone marrow aspiration

15 Normal bone marrow aspirate

16 Normal bone marrow aspirate

17 Acute leukemias

18 Chronic leukemias

19 Non-Hodgkin lymphoma

20 Hodgkin lymphoma

21 Myeloma

22 (Non-specific esterase)
Morphology Regular stain (Wright-Giemsa) Cytochemical stain (Non-specific esterase)

23 Immunophenotyping

24 Normal chromosomes Chromosomes in CML

25 Cytogenetics

26 Molecular Studies cut paste amplify

27 Hematologic Malignancies
Leukemias Acute leukemias Chronic leukemias Lymphomas Hodgkin lymphoma Non-Hodgkin lymphoma Plasma cell disorders Multiple myeloma

28 Hematologic Malignancies
Leukemias Acute leukemias Chronic leukemias

29 Acute vs. chronic leukemia
Acute leukemia Sudden onset Can occur in either adults or children Rapidly fatal without treatment Composed of immature cells (blasts) Chronic leukemia Slow onset Occurs only in adults Longer course Composed of mature cells

30 Acute ALL AML Chronic CLL CML Lymphoid Myeloid

31 Acute ALL AML Chronic CLL CML

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33 Acute lymphoblastic leukemia Acute myeloid leukemia

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35 Chronic myeloid leukemia Chronic lymphocytic leukemia

36 ALL AML CLL CML Lymphoid Myeloid

37

38

39 Hematologic Malignancies
Leukemias Acute leukemias

40 Pathophysiology of Acute Leukemia
Definition: malignant proliferation of immature myeloid or lymphoid cells in the bone marrow Cause Clonal expansion Maturation failure Badness Crowd out normal cells Inhibit normal cell function Infiltrate other organs

41

42 Acute lymphoblastic leukemia Acute myeloid leukemia

43 Acute leukemia: bone marrow biopsy

44 Clinical Findings in Acute Leukemia
Sudden onset (days) Symptoms of bone marrow failure Fatigue Infections Bleeding Bone pain (expanding marrow) Organ infiltration (liver, spleen, brain)

45 Laboratory Findings in Acute Leukemia
Blasts/immature cells in blood Leukocytosis Anemia Thrombocytopenia

46 Hematologic Malignancies
Leukemias Acute leukemias acute myeloid leukemia acute lymphoblastic leukemia

47 Hematologic Malignancies
Leukemias Acute leukemias acute myeloid leukemia

48 Acute Myeloid Leukemia
Things you must know Malignant proliferation of myeloid blasts in blood, bone marrow 20% cutoff for diagnosis Many subtypes Bad prognosis

49

50 Acute Myeloid Leukemia
M0 - acute myeloblastic leukemia, minimally differentiated M1 - acute myeloblastic leukemia without maturation M2 - acute myeloblastic leukemia with maturation M3 - acute promyelocytic leukemia M4 - acute myelomonocytic leukemia M5 - acute monocytic leukemia M6 - acute erythroblastic leukemia M7 - acute megakaryoblastic leukemia

51 Acute Myeloid Leukemia
involve neutrophilic series (myeloblasts, promyelocytes, etc.) involve monocytic series (monoblasts, etc.) involves erythroid series (erythroblasts) involves megakaryocytic series (megakaryoblasts)

52 20% need at least blasts

53 Acute myeloid leukemia: >20% blasts

54 Acute myeloid leukemia: >20% blasts

55 Acute myeloid leukemia

56 AML-M3 (acute promyelocytic leukemia)

57 AML-M6 (acute erythroblastic leukemia)

58 AML-M5 (acute monoblastic leukemia)

59 AML-M5: brain involvement

60 AML-M5: brain involvement

61 AML-M5: gum involvement

62 before (L) and after (R) treatment
AML: gum involvement before (L) and after (R) treatment

63 AML-M0: Acute myeloid leukemia without differentiation

64 Auer rods

65 Treatment and Prognosis of AML
Chemo Bone marrow transplant Prognosis Dismal Some chromosomal abnormalities convert different prognosis If therapy-related, worse prognosis

66 Myelodysplastic Syndrome
Dysmyelopoiesis ± increased blasts May evolve into AML Older patients, usually Asymptomatic or marrow failure Macrocytic anemia Treatment depends on age, aggressiveness

67 Dyserythropoiesis (dysmyelopoiesis in red cells)

68 Dysgranulopoiesis (dysmyelopoiesis in neutrophils)

69 Hematologic Malignancies
Leukemias Acute leukemias acute myeloid leukemia acute lymphoblastic leukemia

70 Acute Lymphoblastic Leukemia
Things You Must Know Malignant proliferation of lymphoid blasts in blood, bone marrow Classified by immunophenotype (B vs. T) More common in children Prognosis often good!

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72 ALL

73 ALL

74 ALL Immunophenotype T-lineage ALL: worse prognosis.
B-lineage ALL: better prognosis.

75 children most common in

76 Treatment and Prognosis of ALL
Chemo ± bone marrow transplant Many children are cured! Prognosis Immunophenotype (T is worse) Age (1-10 better) WBC (<10,000 better) Cytogenetics (hyperdiploidy better!)


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