HPS 301 Myeloid Neoplasms PDF

Myeloid Neoplasms: Chronic myeloid leukemia and Myelodysplastic syndrome Dr Noha Kamal, MBBS, MSc, MD Dep. of Patholo...

Myeloid Neoplasms: Chronic myeloid leukemia and Myelodysplastic syndrome Dr Noha Kamal, MBBS, MSc, MD Dep. of Pathology, GMU www.gmu.ac.ae COLLEGE OF MEDICINE Learning objectives Describe myelodysplastic Neoplasm (MDS) List the types of myeloproliferative neoplasia Define Chronic Myeloid leukemia Enumerate the phases of CML Describe briefly the clinical features of CML in chronic phase. Enumerate the diagnostic evaluation of CML List the differences in lab findings in leukemoid reaction and CML in chronic phase. Myeloid neoplasm: WHO Classification The main three categories: Acute Myeloid Leukemia and related disorders Myeloproliferative Neoplasms (MPN) Myelodysplastic Neoplasms (MDS)  Myelodysplastic Neoplasms (MDS) This is a group of clonal disorders of hemopoietic stem cells characterized by increasing bone marrow failure associated persistent unexplained cytopenia(s) and morphologic dysplasia, and a propensity to progress to BM failure or acute myeloid leukemia. A hallmark of the disease is simultaneous proliferation and apoptosis of hemopoietic cells (ineffective hemopoiesis) leading to a hypercellular bone marrow but pancytopenia in peripheral blood. There is a tendency to progress to acute myeloid leukaemia (AML). Incidence: A disease of the elderly but are also occasionally noted in pediatric age group. Cytogenetic abnormalities: partial or total loss of chromosomes 5 or 7.  Dysplastic blood cells MDS: Morphology Bone marrow Hypercellular bone marrow At least 10% of the cells in a lineage should be dysplastic in order to consider the diagnosis of MDS (Erythroid, Myeloid, Megakaryocytic lineage) Nucleated red cell progenitors Ring sideroblasts with multilobated or multiple nuclei. Myeloproliferative Neoplasms (MPN) Arising from marrow stem cells and characterized by clonal proliferation of one or more haemopoietic components in the bone marrow and, in many cases, the liver and spleen. The major MPN disorders : Chronic Myeloid leukemia: WBCs overproduction particularly neutrophils Polycythemia vera (PV): RBCs overproduction independent of the mechanisms that normally regulate erythropoiesis. Essential thrombocythemia (ET) Primarily involves the megakaryocytic lineage. It is characterized by sustained thrombocytosis in the peripheral blood and increased numbers of large, mature megakaryocytes in the bone marrow and clinically by the occurrence of thrombosis and/or hemorrhage. Primary myelofibrosis (PMF) Is a characterized by a proliferation of predominantly abnormal megakaryocytes and granulocytes in the bone marrow, which in fully developed disease is associated with reactive deposition of fibrous connective tissue and with extramedullary haematopoiesis. Unique Characteristics Patients with CML can lose weight and sweat excessively. The patient can progress to a terminal blast crisis, which carries a poor prognosis. Patients with PV may experience itching, classically after a hot shower. Hyper viscosity (thickened blood caused by massively increased numbers of RBCs) can also induce symptoms, including headaches, visual disturbances, and ruddy or plethoric appearance of the face. Thrombotic events: e.g., deep vein thrombosis. increased hemoglobin level, hematocrit level, and RBC count. Patients with ET may have both bleeding and thrombosis. Patients with PMF often present with a massively enlarged spleen. PB smear: Leucoerythroblastic reaction with tear drop.  Chronic myeloid leukemia (CML) CML is a Myeloproliferative neoplasm of the hematopoietic stem cell with presence of a “Philadelphia chromosome”. [t(9;22)(q34.1;q11.2), BCR-ABL1 positive] Incidence: The disease accounts for around 15% of leukaemias Most frequently 40-60 years (may occur at any age). Male : female ratio of 1.4 : 1 CML may transform into an acute phase and behave like an acute leukemia. Philadelphia chromosome is also +ve in some acute myeloid and lymphoblastic leukemia CML: PATHOGENESIS The diagnosis of CML is assisted by the characteristic presence of the Philadelphia (Ph) chromosome. This results from translocation between chromosomes 9 and 22. The abnormal chromosome 22 is the Ph chromosome. CML: PATHOGENESIS (cont.) The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein. This has tyrosine kinase activity in excess of the normal ABL1* (abnormal tyrosin kinase activity) tyrosine kinase inhibitors (TKIs) to treat CML because they block the BCR- ABL fusion tyrosine kinase. Review Questions ~  CML: CLINICAL FEATURES In up to 50% of cases the diagnosis is made incidentally from a routine blood count Splenomegaly is massive. Bony Pain Anaemia Bleeding tendency : Bruising, epistaxis, menorrhagia or haemorrhage from other sites because of abnormal platelet Stages of Chronic myeloid leukemia: 2. Blast phase 1. (CML-BP), Chronic phase CML in blastic ( CML-CP) crisis myeloplast < 5% blast > 20 % blast or increase lymphoblast Stages of Chronic myeloid leukemia: 1. 2. Chronic Blast phase phase (CML-BP), ( CML-CP) CML in blastic crisis > 20 % < 5% blast blast  Laboratory Diagnosis CBC and Peripheral blood film: WBCs: Leukocytosis with left shift > 50 × 109 /L and sometimes > 500 × 109 /L. with predominance of neutrophils, metamyelocytes, myelocytes Absolute Basophilia Eosinophilia Platelet: variable., thrombocytosis (most frequently), NNA Bone marrow: hypercellular with granulopoietic predominance Blast cell %: according to the stage of CML Cytochemistry : LAP –score/NAP (Leukocyte/Neutrophil alkaline phosphatase) Very low score 0-10 in CML Very high score > 200 in Leukemoid reaction Cytogentic and PCR: positive for Ph chromosome ↑ Serum uric acid  Hypercellular BM CML—Blood smear. (A) Neutrophilia with leftward shift, (B) eosinophilia, (C) basophilia CML in Blast Phase/ crisis Peripheral blood film of a known patient of CML: large blasts ↑ *NAP: A strongly positive (4) and moderately positive (3 and 2) intensity of reaction are shown.  Chronic myeloid leukemia (CML) In up to 50% diagnosed accidentally with a routine blood count Massive splenomegaly Leukocytosis with a myeloid left shift Absolute basophilia Thrombocytosis Philadelphia chromosome is translocation (9 & 22) → BCR-ABL → abnormal tyrosin kinase activity. 2. 1. Blast phase (CML-BP), Chronic phase also known as CML in ( CML-CP) blastic < 5% blast crisis > 20 % blast Review Questions netresultrl a start Review Questions - Readings: Web link : Kumar V, Abbas A K, Aster J C: Robbins Basic Pathology. 10th Ed. Elsevier Saunders Publisher. 2018; Chapter 12, 441-494. ISBN: 978-0-8089-2432-6. Available at the clinical key: http://www.gmu- library.com/resources Khoury, J.D., Solary, E., Abla, O. et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 36, 1703– 1719 (2022). https://doi.org/10.1038/s41375-022-01613-1 Scholar Rx: https://exchange.scholarrx.com/brick/myeloproliferative-neoplasms- foundations-and-frameworks https://exchange.scholarrx.com/brick/chronic-myeloid-leukemia https://exchange.scholarrx.com/brick/myelodysplastic-neoplasms