MYELOPROLIFERATIVE DISEASE. Dr Mere Kende MBBS (UPNG), MMED (Path),MAACB, MACTM, MACRRM (Aus) Lecturer-SMHS UPNG

Transcription

1 MYELOPROLIFERATIVE DISEASE Dr Mere Kende MBBS (UPNG), MMED (Path),MAACB, MACTM, MACRRM (Aus) Lecturer-SMHS UPNG

2 Myeloproliferative Diseases Essential to diagnosis Acquired clonal abnormalities of the hematopoietic stem cell Stem cell gives origin ----qualitative and quantitative changes are seen in all these cell lines. CML- specific characteristic chromosomal changes are seen. Morphological abnormalities to 2 or more cells lines

3 Normal Hemopoiesis

4 CLASSIFICATIONS Myeloproliferative syndromes Polycythemia vera (erythroid precursors) Myelofibrosis (fibroblast) Essential thrombocytosis (thrombocytes/megakaryocyte) Chronic myeloid leukemia (myeloid) Myelodysplastic syndromes Acute myeloid leukemia

5 Myeloproliferative Disease Can evolve from one for to another All Disorders can Progress to AML

6 Clinical Features of MPD Generalised Fatique, FUO Anemia Increased risk of Infections/Night sweats Increased thrombotic episodes Organomegaly (liver & spleen) Hyperviscosity Syndrome

7 Cause Idiopathic/Unknown Post-cytotoxic Chemotherapy

8 Polycythemia Vera Essentials of Diagnosis Increased red blood cell mass (>60%). Splenomegaly (75%). Normal arterial oxygen saturation. Usually elevated white blood count ( /mcl) and platelet count ( /mcl).

9 Polycythemia Vera

10 Normal Blood Film

11 Other Features Hyperviscocity/increased thrombosis Iron deficiency Hypercellular marrow High vitamin B12 (increased transcobalamin III) Hyperuricemia

12 Causes

13 Treatment Weekly phlebotomy (aim PCV<45%) Myelosuppressive therapy (hydroxyurea) Allopurinol (hyperuricemia)

14 Essential Thrombocytosis Defect in stem cells Marked proliferation of the megakaryocytes in BM Elevation of Platelet Counts Median Age: 50 60; W>M

15 Essential Thrombocytosis Thrombosis (abdomen) Burning sensation of tips of finger Splenomegaly (25%) BM increased megakaryocytes WBC<30,000/mcl

16 Essential Thrombocytosis Essentials of Diagnosis Elevated platelet count in absence of other causes >2million/mcl (reactive usu<1million/mcl) Normal red blood cell mass. Absence of Philadelphia chromosome.

17 Treatment Hydroxyurea Aspirin (thrombosis)

18 Myelofibrosis Bone Marrow fibrosis (increased PDGF/cytokines) Increased extra-medullary hemopoiesis

19 Other Features Age: 50 years Fatiue & Anaemia Bleeding uncommon Massive splenomegaly (common) Hepatomegaly (50%) Portal hypertension, ascites, esophageal varices,

20 Laboratory Features Anemia Blood Film Teardrop poikilocytosis on peripheral smear. Leukoerythroblastic blood picture; giant abnormal platelets.

21 Blood Film- Tear drops red cells

22 Bone Marrow -Fibrosis

23 Myelofibrosis Essentials of Diagnosis Striking splenomegaly. Teardrop poikilocytosis on peripheral smear. Leukoerythroblastic blood picture; giant abnormal platelets. Hypercellular bone marrow with reticulin or collagen fibrosis.

24 Treatment Medical (thalidomide/erythropoeitin) Transfusion Transplant

25 Chronic Myelogenous Leukemia Essentials of Diagnosis Strikingly elevated white blood count (>150,000/mcl). Markedly left-shifted myeloid series but with a low percentage of promyelocytes and blasts <5%). Presence of Philadelphia chromosome or bcr/abl gene

26 Philadelphia Chromosome

27 Other Features Median age: 55 years Fatigue, sweats, Low grade Fever Abdominal fullness/splenomegaly WBC usually >500,000/mcL. Expanding BM - sternal tenderness, bone pain, FUO

28 CML

29 CML- Increased WBC

30 Bone Marrow-Increased M: E ratio

31 CML Bone Marrow Hypercellular, increased myeloid/megakaryocyte/no fat

32 Treatment Medical Hydroxyurea Bulsulpan Interferon apha-b2 (expensive) -injections Allopurinol (hyepruricemia) Radiation

33 Summary of Laboratory Findings

34 Myelodysplastic Syndromes Essentials of Diagnosis Cytopenias with a hypercellular bone marrow. Morphologic abnormalities in two or more hematopoietic cell lines. Blast cells <20% (cf AML)

35 General Considerations Acquired clonal disorders of the hematopoietic stem cell. Characteristcis: Cytopenias, a usually hypercellular marrow, an A No. of morphologic and cytogenetic abnormalities. Cause: idopathic or post-cytotoxic chemotherapy. Transform to AML (hence termed also as preleukemia) Includes various diagnoses/syndrome Refractory Anemia without Excess Blasts Refractory anemia with excess blasts" (RAEB 5 19% blasts). Chronic myelomonocytic leukaemia (monocytosis > 1000/mcL

36 Clinical Findings Age: >60 years. Asymptomatic incidental abnormal FBE findings Symptomatic: fatigue, infection, or bleeding related to bone marrow failure, wasting illness with fever, weight loss, and general debility. Exam: +/-splenomegaly with pallor, bleeding, and various signs of infection.

37 Laboratory Findings Anemia (MCV normal or may be increased ) Macro-ovalocytes WBC count usually normal or reduced, Neutropenia is common +/-morphologic abnormalities,) Left-shifted myeloid series (promyelocytes or blasts) Platelets normal or reduced, and hypogranular platelets may be present

38 PERIPHERAL BLOOD 50 x.) PMN cellshyposegmentation (socalled Pelger-Huet anomaly) as well as hypogranularity. While not present in all patients with myelodysplastic syndrome, these findings would be very suggestive of this diagnosis as the underlying disorder. (Courtesy of L Damon.)

39 BONE MARROW Hypercellular / Erythroid hyperplasia is common, Signs of abnormal erythropoies (megaloblastic features, nuclear budding, or multinucleated erythroid precursors (see micrograph). The Prussian blue stain may demonstrate ringed sideroblasts. Left-shifted myeloid series Dwarf megakaryocytes with unilobed nucleus Variety of cytogenetic abnormalties (chrmosomal deletions)

40 Bone Marrow Myelodysplastic syndrome. (Bone marrow aspirate, 100 x.) Increased erythroid cells with basophilic cytoplasm. Abnormal looking RBC precursors & megaloblastic picture, dysmorphic granulocyte maturation or megakaryocyte maturation (Courtesy of L Damon.)

41 Treatment Traditionally no effective therapy Supportive: RBC transfusions. Recently, Erythropoietin (epoetin alfa), Lenalidomide (70% response rate, expensive Azacitidine (5-azacytidine)-primary choice Immuno-suppresive therapy Stem cell transplants

42 Course & Prognosis Fatal if untreated Transplant 30-60% cure Risk of transformation AML with higher blasts cells Poor prognosis with cytogenic abnormalities

43 Acute Myeloid Leukaemia Myelogenous/myeloid leukaemia Abnormality in myeloid line of cells (granulocytes, monocytes, erythroids, megakaryocytes) Proliferation of abnormal myeloid cells and failure to differentiate to normal mature cells Suppressed normal myeloid cell line (granulocytes, monocytes, platelets, red cells) RESULTS: malignant blast cells--anemia, risk of infections, bleeding tendencies

44 Epidemiology AML is seen 80% of time in adults; only <10% in children (<10 yrs) Median age: 65; 2x common in males

45 Association/Risk factors Chemical exposure Radiation Tobacco Chemotherapy Trisomy 21 (Down s syndrome) Fanconi Anaemia Aplastic anaemia Myeloid dysplasia Myeloproliferative diseases (CML; ET; MF;PV)

46 Clinical Presentation Non-specific symptoms: wt loss, fatigue Anemia (pallor; tachycardia) Bleeding (gingival; epistaxis; ecchymoses, menorrhagia)----thrombocytopenia Infections (mild-severe) Onset weeks-months Promonomyelocytic CNS symptoms; gum hypertrophy) Lymphadenopath----less common Splenomegaly/hepatomegaly-----if transformed from MPD/CML

47 Tumour lysis Syndrome Hyperphosphatemia Hypocalcemia Hyperuricemia Hyper/hypokalemia Lactic acidosis Hypoxaemia

48 Laboratory tests FBE: low Hb (normochromic, normocytic) Thrombocytopenia <100,000 x/mcl (75%) Low reticulocytes (retics) Leukocytosis >100,000 /mcl (20%); <5,000 (20-40%); median 15,000 BLAST CELLS (>20% diagnostic) if less examine BM

49 Myeloblasts Immature; large nucleus; prominent nucleoli Pale-blue cytoplasm AUER RODS Myeloperoxidase +ve Flow cytometry-characteristic antigen panel

50 Myeloblasts Immature; large nucleus; prominent nucleoli Pale-blue cytoplasm Myeloperoxidase +ve AUER RODS

51

52 Flow cytometrycharacteristic antigen panel

53 Bone Marrow biopsy/aspirate Key to diagnosis of AML Hypercellular BLAST cells (>20%) Decreased normal cells Small percents may have hypocellular BM

54 Prognostic/Choice of treatment Flow cytometry Cytogenetics infromation molecular studies (latest)

55 Differential Diagnosis ALL No auer rods Negative myeloperoxidase Negative sudan black stain Flow cytometry ( different antigen panels) Cytogenics (t (1,22)- with AML

56 Treatment Supportive Adults >65yrs-poor prognosis Chemotherapy on selected cases Overall only <20% live more than 5 years

57 References Current Medical Diagnosis and Treatment 2008 LG. Gomella, SA. Haist; Clinicians Pocket Reference 11 th Edition 2007 Harrison s Text of Medicine 17 th Edition

58