ACUTE LEUKEMIA and Leucopenia

ACUTE LEUKEMIA:

ACUTE LEUKEMIA

DEFINITION:

DEFINITION Failure of cell maturation Proliferation of immature cells which fill up marrow Ultimately immature cells spill over to peripheral blood

Classification of leukemias:

Classification of leukemias Acute Chronic Myeloid origin Lymphoid origin Acute Myeloid Leukemia (AML) Acute Lymphoblastic Leukemia (ALL) Chronic Myeloid Leukemia (CML) Chronic Lymphocytic Leukemia (CLL)

Leukemia Classification:

Leukemia Classification Acute Leukemias: Myeloid - M0, M1, M2, M3, M4, M5, M6, M7 Lymphoid - L1, L2, L3. Chronic Leukemias: Myeloid - CML Lymphoid- CLL, PLL, HCL,

Myeloid maturation:

Myeloid maturation myeloblast promyelocyte myelocyte metamyelocyte band neutrophil MATURATION Adapted and modified from U Va website

Acute Leukemia:

Acute Leukemia accumulation of blasts in the marrow myeloblast promyelocyte myelocyte metamyelocyte band neutrophil

Myeloblasts with auer rods:

Myeloblasts with auer rods

AML-M3 - Auer Rods:

AML-M3 - Auer Rods

Lymphoblast:

Lymphoblast

Causes of acute leukemias:

Causes of acute leukemias idiopathic (most) underlying hematologic disorders chemicals, drugs ionizing radiation viruses (HTLV I) hereditary/genetic conditions

CLINICAL FEATURES:

CLINICAL FEATURES Fever Anemia Thrombocytopenia Bone pain tenderness (Sternal), Migrating joint pains Leukemic infiltration of tissues Hepatosplenomegaly Lymphadenopathy Gum hypertrophy Soft tissues (Chloroma) Intracerebral leukocytostatis (BALL’s disease) (AML) Leukemic meningitis (ALL)

Clincal manifestations:

Clincal manifestations symptoms due to: marrow failure tissue infiltration leukostasis constitutional symptoms other (DIC) usually short duration of symptoms

Marrow failure:

Marrow failure neutropenia: infections, sepsis anemia: fatigue, pallor thrombocytopenia: bleeding

Infiltration of tissues/organs:

Infiltration of tissues/organs enlargement of liver, spleen, lymph nodes gum hypertrophy bone pain other organs: CNS, skin, testis, any organ

Gum hypertrophy:

Gum hypertrophy

AML-M5 - Gum Hypertrophy::

AML-M5 - Gum Hypertrophy:

ALL:Cervical Lymphadenopathy:

ALL:Cervical Lymphadenopathy

Cervical Lymphadenopathy:

Cervical Lymphadenopathy

Chloromas:

A B C Chloromas NEJM 1998

Organomegaly :

Organomegaly

Mediastinal Lymphnodes-ALL:

Mediastinal Lymphnodes-ALL

Leukostasis:

Leukostasis Accumulation of blasts in microcirculation with impaired perfusion lungs: hypoxemia, pulmonary infiltrates CNS: stroke Only seen with WBC >> 50 x 10 9 /L

Slide 23:

ALL AML Age Common- children Adults Bleeding Less More Lymphadenopathy More Less Hepatosplenomegaly Majority Less CNS More (Meningitis) BALL’S Gum Hypertrophy -------- Common Testicular involvement 10 to 20% Less Eye More Less

Slide 24:

ALL AML Cytochromal staining Myeloperoxidase -ve +ve Sudan Black -ve +ve Periodic Acid Schiff (PAS) +ve in > 50% cells +ve in < 25% cells

LAB INVESTIGATIONS:

LAB INVESTIGATIONS Normocytic / Normochromic Anemia Thrombocytopenia  Total count (20,000 to 50,000 cells) Peripheral blood smear – Numerous blast cells Marrow – Blast cells > 20% (Nucleated cells) X-Ray chest – Mediastinal widening

MANAGEMENT:

MANAGEMENT Supportive Anemia – Blood Transfusion Thrombocytopenia – Platelet Transfusion Infection – Blood culture and sensitivity Barrier nursing

How to distinguish AML vs CML from looking at peripheral blood:

How to distinguish AML vs CML from looking at peripheral blood Myeloid cell CML AML Normal blasts q q promyelocytes q myelocytes q metamyelocytes q bands q neutrophils q # q

SUB LEUKEMIC LEUKEMIA:

SUB LEUKEMIC LEUKEMIA Counts normal Abnormal cells in Peripheral Blood Smear

ALEUKEMIA LEUKEMIA:

ALEUKEMIA LEUKEMIA Counts normal No abnormal cells in peripheral blood smear Marrow shows abnormal cells

LEUKEMOID REACTION:

LEUKEMOID REACTION Counts elevated (25,000 to 30,000 cells) Usually mature cells; toxic granules can be seen No blasts Bone Marrow – Accelerated Leucopoiesis Myeloid reaction – Infection, TB, Hemolytic Anemia Lymphoid reaction – IM, CMV, VZ, Carcinomas

MDS:

MDS A leukemia related condition Anemia, Neutropenia, Thrombocytopenia Normo / Hyper cellular marrow Blast area seen in marrow < 20% It can transform to AML

AML:

AML M1 – Myloblast without maturation (Non granular cytoplasm) M2 – Myloblast with maturation (more mature cells seen) M3 – Hypergranular “ Promyelocytic ” Leukemia M4 – Myelomonocytic Leukemia – Both Myeloid / Monocyte immature cells M5 – Monocytic Leukemia M6 – Erythroleukemia (Erythroblasts>50%, marrow with immature myeloblasts) M7 – Megakaryoblastic Leukemia (  Megakaryoblasts)

ALL:

ALL L1 – Homogenous small lymphoblasts L2 – Heterogenous Lymphoblasts L3--Homogenous large lymphoblasts

POOR PROGNOSTIC FEATURES:

POOR PROGNOSTIC FEATURES Increasing age Male sex High leucocyte count at diagnosis CNS involvement at diagnosis Antecedent hematological disorder Cytogenetic abnormalities

Slide 35:

Drugs commonly used in the treatment of Acute Leukemia Phase Lymphoblastic Myeloid Induction Vincristine (IV) Prednisolone (Oral) L-Asparaginase (IV) Daunorubicin (IV) Methotrexate (Intrathecal) Daunorubicin (IV) Cytarabine (IV) Etoposide (IV & Oral) Tioguanine (Oral) Consolidation Daunorubicin (IV) Cytarabine (IV) Etoposide (IV) Methotrexate (IV) Cytarabine (IV) Amascrine (IV) Mitoxantrone (IV & Oral) Maintenance Prednisolone (Oral) Vincristine (IV) Mercaptopurine (Oral) Methotrexate (Oral

Slide 36:

Diagnosis Specific therapy ? Induction Remission Remission consolidation Maintenance therapy No further treatment Bone marrow transplantation Supportive Therapy only Relapse No Yes

Leucopenia :

Leucopenia Reduction in WBC Count (Individual / All) Neutropenia Typhoid / Viral Leukemia Drugs / — Carbimazole / Carbamazepine

Slide 38:

Agranulocytosis Reduction in granulocytes (Neutrophils, Eosinophils, Basophils Lymphopenia Drugs / Renal Failure

Bone Marrow Transplant:

Bone Marrow Transplant Allogenic Related donor Volunteer donor Autologous Patient Stem cell harvested from Bone Marrow Peripheral blood Infused IV HLA - Matched

Side Effects:

Side Effects GVHD Infections