Acute Leukemia Kristine Krafts, M.D.

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

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

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

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

Bone marrow biopsy needle

Bone marrow biopsy: cellularity

Normal bone marrow biopsy

Normal bone marrow biopsy

Bone marrow aspiration needle

Bone marrow aspiration

Normal bone marrow aspirate

Normal bone marrow aspirate

Acute leukemias

Chronic leukemias

Non-Hodgkin lymphoma

Hodgkin lymphoma

Myeloma

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

Immunophenotyping

Normal chromosomes Chromosomes in CML

Cytogenetics

Molecular Studies cut paste amplify

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

Hematologic Malignancies Leukemias Acute leukemias Chronic leukemias

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

Acute ALL AML Chronic CLL CML Lymphoid Myeloid

Acute ALL AML Chronic CLL CML

Acute lymphoblastic leukemia Acute myeloid leukemia

Chronic myeloid leukemia Chronic lymphocytic leukemia

ALL AML CLL CML Lymphoid Myeloid

Hematologic Malignancies Leukemias Acute leukemias

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

Acute lymphoblastic leukemia Acute myeloid leukemia

Acute leukemia: bone marrow biopsy

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)

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

Hematologic Malignancies Leukemias Acute leukemias acute myeloid leukemia acute lymphoblastic leukemia

Hematologic Malignancies Leukemias Acute leukemias acute myeloid leukemia

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

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

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

20% need at least blasts

Acute myeloid leukemia: >20% blasts

Acute myeloid leukemia: >20% blasts

Acute myeloid leukemia

AML-M3 (acute promyelocytic leukemia)

AML-M6 (acute erythroblastic leukemia)

AML-M5 (acute monoblastic leukemia)

AML-M5: brain involvement

AML-M5: brain involvement

AML-M5: gum involvement

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

AML-M0: Acute myeloid leukemia without differentiation

Auer rods

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

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

Dyserythropoiesis (dysmyelopoiesis in red cells)

Dysgranulopoiesis (dysmyelopoiesis in neutrophils)

Hematologic Malignancies Leukemias Acute leukemias acute myeloid leukemia acute lymphoblastic leukemia

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!

ALL

ALL

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

children most common in

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!)