Nada Mohamed Ahmed, MD, MT (ASCP)i

Objectives

chronic myeloid leukaemia (CML) Haematopoietic malignancies Polycythemia vera (PV) Idiopathic myelofibrosis (MF) Essential thrombocythemia (ET) Acute myeloid leukaemia (AML) Chronic myeloid leukaemia (CML) Acute lymphatic leukaemia (ALL) Chronic lymphatic leukaemia (CLL) Hodgkin’s lymphoma Burkitt's lymphoma cutaneous T-cell lymphoma (CTCL) Non-hodgkin’s lymphoma (NHL) Myeloproliferative diseases Leukaemias Malignant lymphomas

Definition: Clonal haematopoeitic disorders Proliferation of one of myeloid lineages – Granulocytic – Erythroid – Megakaryocytic Relatively normal maturation 4

5 Most common diseases included in the : – Chronic myelogenous leukemia (CML) – Polycythemia rubra vera (PRV or PV) – Essential thrombocythemia (ET) – Myelofibrosis (MF) Clinically, patients with MPD present in a clinically stable phase that may transform to an aggressive cellular growth phase such as acute leukemia or just a more aggressive form of MPD classification of MPDs

Clinical features Non-specific features common to all, due to a hypermetabolic state a. Fever, weight loss and drenching night sweats b. Splenomegaly : most prominent in MF and CML Specific features such as bleeding or thrombosis in PRV and ET All may be incidentally discovered on routine physical or laboratory tests 6

Chronic Myelogenous Leukemia (CML) second most common leukemia middle aged excess number of “mature” all stages of maturation in bone marrow chromosomal abnormality Philadelphia chromosome t(9;22)

Chronic Myelogenous Leukemia (CML) laboratory WBC : >100,000 Thrombocytosis Numerically increased, but functionally impaired granulocytes

Chronic myeloid leukemia (CML)

The Philadelphia Chromosome XY19

The Philadelphia Chromosome: t(9;22) Translocation bcr-abl Fusion protein with tyrosine kinase activity 22 bcr abl Ph 9 9+ Philadelphia chromosome

Clinical Course: Phases of CML Chronic phase Median 4–6 years stabilization Accelerated phase Median duration up to 1 year Blastic phase (blast crisis) Median survival 3–6 months Terminal phase Advanced phases

13 Polycythemia rubra vera (PV) A neoplastic, clonal overproduction of erythrocytes, granulocytes, and platelets to some degree (primary problem is too many RBCs) The clonal neoplastic transformation arises in a pluripotential hematopoietic stem cell RBCs are very sensitive to erythropoietin for cell growth Disease progresses to acute leukemia in 15% of cases Primary treatment is therapeutic phlebotomy

Polycythemia rubra vera (PV) Increased Red Blood Mass Increased Blood Volume And Viscosity (hyperviscosity syndrome) BM:hypercellularerythroid, megakaryocytic & granulocytic hyperplasiamay eventually become fibrotic 14

15 Essential Thrombocythemia (ET) Manifests with increased megakaryocytopoiesis and peripheral blood thrombocytosis. PLT counts greater than 600,000/Μl. Complications include thromboembolism and hemorrhage.

Myelofibrosis Bone Marrow Fibrosis: replacement of bone marrow with collagenous connective tissue fibers middle aged adults (50-60 y/o) extramedullary hematopoiesis (spleen, liver) may occur as an extension of CML or PV abnormal peripheral RBCs (“tear-drop” & nucleated RBCs) immature WBC and abnormal platelets infection, thrombosis and hemorrhage as a major complication

18 Myelofibrosis - laboratory findings Peripheral blood smear:anisocytosis and poikilocytosis with the presence of teardrop- shaped and nucleated red cells, immature neutrophils but myeloblasts not always Aspiration of bone marrow is usually unsuccessful Smears from successful aspirates usually show neutrophilic and megakaryocytic hyperplasia Trephine biopsy often shows a hypercellular marrow with increased reticulin fibers and variable collagen deposition. Increased numbers of megakaryocytes are frequently seen.

Myelofibrosis Aniso-poikilocytosis leukemoid reaction “naked” nuclear fragments

Case History A 58 year old man is admitted for elective repair of an inguinal hernia. Routine CBC : Hb g/dl, PCV 0.61; WBC 16 x 10 9 /L; platelets 520x 10 9 /L Physical examination: enlarged spleen He admits to having recurrent headache and blurred vision for the past 6 months 20

1.Chronic myelogenous leukemia (CML) 2.Polycythemia rubra vera (PRV or PV) 3.Essential thrombocythemia (ET) 4.Myelofibrosis