1. 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.

2. 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)/

3. 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

4. Normal bone marrow

5. 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

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

7. 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

8. 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

9. 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

10. 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

11. 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

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

13. 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].

14. 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].

15. Changes in oral cavity in AL

16. Gingival hyperplasy in leukemia

17. Papulous and necrotic changes in oral cavity are typical for AL

18. Leucoplakia in leukemia

19. 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

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

21. 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.

22. 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.

23. Bone marrow in myeloleukosis

24. 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

25. Myeloblastic leukemia
lymphoblastic leukemia

26. Acute non-differentiated leukemia

27. CHRONIC LEUKEMIA

28. 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.

29. 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.

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

31. lymphadenopathy

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

33. 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 mg daily initially, with subsequent gradual dose reduction, may be useful in patients with autoimmune manifestations of the disease.

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

35. 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.

36. 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.

37. 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.

38. HEPATOSPLENOMEGALY

42. 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.

43. Accelerated phase,
which may last for several months. The survival of patients diagnosed in this phase is 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.

44. 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.

45. blast crisis

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

47. 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.