Leukaemias and lymphomas. Etiology, pathogenesis. Diagnostics Leukaemias and lymphomas. Etiology, pathogenesis. Diagnostics. Clinical pattern. Principles of treatment. Typical changes in oral cavity in agranulocytosis and leukaemias. The role of  a doctor-dentist   in early diagnostics and prophylaxis N. Bilkevych Copyright, 1996 © Dale Carnegie & Associates, Inc.

Hemoblastoses Group of tumours which arise out of blood cells. Hemoblastoses, at which bone marrow is fully populated with tumour cells, are named leukaemias. A. Primary bone marrow affection (leukemia) B. Secondary bone marrow affection (lymphosarcoma etc)/

Hemopoiesis and Lymphopoiesis Pluripotent Stem Cells Most primitive cells Mature blood cells and lymphocytes develop from pluripotent cells The pluripotent stem cells differentiate into either myeloid stem cells or lymphoid stem cells The myeloid stem cells produce progenitors Progenitors lead to the production of mature functional cells

Normal bone marrow

Leukemia Is a malignant hematologic disorder characterized by a proliferation of abnormal white cells that infiltrate the bone marrow, peripheral blood and organs 4 main types of leukemia Acute or chronic Myelogenous or Lymphocytic

Main Types Acute Lymphocytic Leukemia (ALL) Acute Mylogenous Leukemia (AML) Chronic Lymphocytic Leukemia (CLL) Chronic Mylogenous Leukemia (CML)

Types of Leukemia Acute Leukemia Chronic Leukemia progresses quickly characterized by the proliferation of undifferentiated cells in the bone marrow Chronic Leukemia slower progression uncontrolled expansion of mature cells

Types of Leukemia Acute and chronic leukemia are further subdivided into: Myelogenous Leukemias those that are from hemopoietic stem cells Lymphocytic Leukemias arise from any other cells in the bone marrow

Types of Leukemia Acute Rapid growth of immature blood cells Mostly in children, young adults Needs immediate treatment Chronic Excessive build up of mature blood cells Mostly in older patients Monitoring before treatment Lymphoid Affects lymphocytes and plasma cells Lymphocytic leukemia Myeloid Affects eosinophils, neutrophils, basophils Myelogenous leukemia

Types of Leukemia Acute Lymphocytic/Lymphoblastic Leukemia(ALL) : most common type in young children; also affects adults, > 65 Acute Myelogenous/ Myeloid Leukemia(AML) more commonly in adults than in children. Chronic Lymphocytic leukemia (CLL) most often affects adults over the age of 55 Chronic Myelogenous leukemia (CML) occurs mainly in adults

Leukemia Symptoms The leukemic cells accumulate in the bone marrow When there are excessive white blood cells --> Infections When there are few red blood cells: Paleness --> Anemia When there are few platelets --> Excessive bleeding

Symptoms Anemia, thrombocytopenia, neutropenia fatigue pallor bleeding infection Clinical pattern of AL includes 4 main syndromes: Hyperplastic Hemorrhagic Anemic Intoxication

Hyperplastic syndrome Moderate and painless enlargement of lymph nodes, spleen and liver. In 25% of patients – marked enlargement of tonsils, their tissue is loose, with hemorrhagic focuses. Also may be found skin infiltration with blast cells – leukaemids. They look like red-violet papuloformic plates in derma. [1].

Hyperplasy of intrathoracic lymph nodes (8%) – dyslpoe, cyanosis, neck swelling, pulsation of neck veins. Gingival hyperplasy (5%) is observed ib severe caurse and is often estimated as unfavorable sign. [1].

Changes in oral cavity in AL

Gingival hyperplasy in leukemia

Papulous and necrotic changes in oral cavity are typical for AL

Leucoplakia in leukemia

Stages of hemoblastoses: Initial stage Period of clinical manifestation is not homogeneous. The clinical synptoms of the first attack are differ from a relapse as a result of citostatic therapy Remission. May be complete and incomplete Recovery – complete remission within 5 and more years Terminal stage

Tests For Diagnosis Blood sample Bone marrow sample Spinal Tap/Lumbar Puncture

Diagnostics of chronic leukosis The criterion of diagnosis of leucosis is an exposure of increased amount of blast cells in marrow, and for some patients - and in blood. Diagnosis of acute leukemia proposed at presence of 30% and more blast cells in a myelogram.

Identification of basic forms of leukemia is conducted primary for every patient with assessment of marrow punctate or trepanobioptate of iliac bones. To recognize the type of blasts (are they of myeloid or lymfoid row) it is possible by cytochemical marker reactions: positive RAS-reaction on glycogen is characteristic for acute lymphoblastic leucosis.

Bone marrow in myeloleukosis

Pictures Of Blood Normal human blood Blood with leukemia White Cell Red Cell Platelet Blood with leukemia Blasts Red Cell Platelet White Cell Sources from beyond2000.com Sources from Arginine.umdnj.edu

Myeloblastic leukemia lymphoblastic leukemia

Acute non-differentiated leukemia

CHRONIC LEUKEMIA

Chronic lymphocytic leukemia (CLL) is a monoclonal disorder characterized by a progressive accumulation of functionally incompetent lymphocytes. The cells of origin in the majority of patients with CLL are clonal B cells arrested in the B-cell differentiation pathway, intermediate between pre-B cells and mature B cells.

Morphologically in the peripheral blood, these cells resemble mature lymphocytes. B-CLL lymphocytes typically show B-cell surface antigens, as demonstrated by CD5, CD19, CD20, CD21, and CD24 monoclonal antibodies.

CLINICAL Localized or generalized lymphadenopathy Splenomegaly (30-40% of cases) Hepatomegaly (20% of cases) Petechiae Pallor

lymphadenopathy

Lab Studies: CBC count with differential shows absolute lymphocytosis with more than 5000 lymphocytes/mL. Increased lymphocytes more than 30% in the bone marrow.

TREATMENT Patients at stage 0 whose disease is stable require only periodic follow-up. Early treatment has not been demonstrated to be advantageous. Prednisolone alone, usually in a dose of 20-60 mg daily initially, with subsequent gradual dose reduction, may be useful in patients with autoimmune manifestations of the disease.

Alkylating agents: Chlorambucil (Leukeran). Nucleotide analogs: Fludarabine (Fludara). Antineoplastic agents: Alemtuzumab (Compath).

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate. Consequently, the peripheral blood cell profile shows an increased number of granulocytes and their immature precursors, including occasional blast cells.

CLINICAL Nonspecific symptoms of tiredness, fatigue, and weight loss may occur long after the onset of the disease. Loss of energy and decreased exercise tolerance may occur during the chronic phase after several months.

Symptoms related to enlargement of the spleen and/or the liver often are present. The enlarged spleen also may be associated with a hypermetabolic state, fever, weight loss, and chronic fatigue.

HEPATOSPLENOMEGALY

The disease has 3 clinical phases, and it follows a typical course of an initial chronic phase, in which the disease process is easily controlled; followed by a transitional and unstable course (accelerated phase); and, finally, a more aggressive course (blast crisis), which usually is fatal.

Accelerated phase, which may last for several months. The survival of patients diagnosed in this phase is 1-1.5 years. This phase is characterized by poor control of the blood counts with myelosuppressive medication and the appearance of peripheral blast cells (15%), promyelocytes (30%), basophils (20%), and platelet counts less than 100,000 cells/L unrelated to therapy. The doses of the medications need to be increased; splenomegaly may not be controllable by medications, and anemia can worsen. Bone pain and fever, as well as an increase in bone marrow fibrosis, are harbingers of the last phase.

Acute phase, or blast crisis, is similar to acute leukemia, and survival is 3-6 months at this stage. Bone marrow and peripheral blood blasts of 30% or more are characteristic. Skin or tissue infiltration also defines blast crisis. Cytogenetic evidence of another Ph-positive clone (double) or clonal evolution (other cytogenetic abnormalities such as trisomy 8, 9, 19, or 21, isochromosome 17, or deletion of Y chromosome) usually is present.

blast crisis

TREATMENT Myelosuppressive agents: Hydroxyurea (Hydrea) Busulfan (Myleran) Imatinib mesylate (Gleevec) Interferon alfa-2a (Roferon A) or alfa-2b (Intron A)

Allogeneic bone marrow or stem cell transplantation is the best treatment for cure of this disease. Unfortunately, this procedure has a high mortality rate because of the induction and long-term complications.