10 MYELODYSPLASTIC SYNDROME MIHS.pptx12355

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1. MYELODYSPLASTIC SYNDROME [MDS] SHARWAN KUMAR YADAV Hematologist M.Sc. MLT (Hematology & Blood Transfusion) St.Johns Medical College & Hospital Department Head of Hematology Crystal Diagnostic Lab Sinamangal Kathmandu

2. LEARNING OBJECTS

3. INTRODUCTION

4. DEFINITION - Myelodysplastic syndromes (MDS) are group of acquired clonal stem cell disorders characterized by progressive cytopenia, dysplasia in one or more myeloid lineages, ineffective hematopoiesis and increased risk of development of AML.

5. CLASSIFICATION- Idiopathic or primary MDS : It is a disease of elderly usually over 50 years of age and often develops gradually. Secondary/therapy-related MDS (t-MDS) : It is a complication of previous cytotoxic drug or radiation therapy. Certain inherited hematological disorders like Fanconi anemia, dyskeratosis congenita and Diamond- Blackfan syndrome are also associated with increased risk of MDS.

6. WHO CLASSIFICATION OF MDS

7. ETIOLOGY AND PATHOGENESIS Some people have a history of exposure to chemotherapy or  radiation  known to cause DNA damage Workers in some industries with heavy exposure to hydrocarbons such as the petroleum industry have a slightly higher risk of contracting the disease than the general population.  Xylene  and  benzene  exposures have been associated with myelodysplasia. Children with  Down syndrome  are susceptible to MDS, and a family history may indicate a hereditary form of  sideroblastic anemia  or  Fanconi anemia .

8. Cont.. In primary MDS the exact cause is not known, however genetic factors may play a role. The causes of secondary /t-MDS are radiation, benzene, post-chemotherapy, viruses, cigarette smoking and PNH. Even though MDS is a group of heterogeneous diseases, a common factor is that they are the result of proliferation of abnormal stem cells. The exact pathogenesis is not known.

9. The initiating defect in most cases is at the level of common myeloid precursor cell, because MDS rarely transforms into acute lymphoid leukemia. The causative factors lead to stem cell mutation and proliferation. There is also increased apoptosis of bone marrow progenitors causing ineffective hematopoiesis. The common chromosomal abnormalities noted are monosomies 5 and 7, deletions of 5q, 7q and 20q.

10. CLINICAL FEATURES Age : A disease of old age, mean age being 65 years with slight male preponderance. In India mean age at presentation is 45 years. Pallor : Gradual onset of weakness, dyspnea and pallor. Splenomegaly : Spleen is just palpable in about one- fourth of the cases History of previous chemotherapy/radiation exposure gives a clue to secondary MDS. Bleeding manifestations : bleeding from gums are present in some cases only. Infections : Skin and respiratory infections due to neutropenia may be the presenting complaint in some of the cases.

11. Cont.. The majority of patients present with symptoms related to cytopenia Most patients are anemic, whereas neutropenia and thrombocytopenia are less common And about one third of patients are dependent on red blood cell transfusions at diagnosis. Organomegaly is infrequently observed.

12. HAEMATOLOGICAL FEATURES Anaemia : RBC – Macrocytic or normocytic or dimorphic but occasionally hypochromic, normoblasts are seen ,basophilic stippling,howell jolly bodies,tear drop cells,stomatocytes,elliptocytes . Few nucleated red cells may be present. 2. White Cells : There is neutropenia, with few blasts. No. of blasts determines the type of MDS. Neutrophils with band shaped nuclei are seen There is hyposegmentation of nuclei and the cytoplasm is hypogranular and ring nuclei may be present. TLC is normal/low. Few eosinophils demonstrate eosino -basophilic granulation.

13. . . . 3. Platelets : Majority of the cases demonstrate variable degree of thrombocytopenia. Smear shows presence of large platelets which lack granules. Platelets are increased in 5q- syndrome. 4. NAP score : Moderately to markedly decreased (Normal 40-100).

14. BONE MARROW MDS is characterized by cellular marrow with ineffective haematopoiesis which results in cytopenia's. Hypercellularity : In majority of the cases, marrow is hypercellular to a variable degree, however, it may be hypocellular in about 10% of the cases. Dyserythropoiesis : There is erythroid hyperplasia with megaloblastic Reaction With Features Of dyserythropoiesis like nuclear budding, irregular nuclei. Howel Jolly bodies in cytoplasm of normoblasts. ring sideroblasts. some of the normoblasts demonstrate internuclear bridging. in advanced MDS cases, erythroid hypoplasia develops. multinucleation of erythroblasts

15. 3. Dysmyelopoiesis : There is myeloid hyperplasia with: hypo granulation of myelocytes, metamyelocytes increase in myeloblasts 5-19% (Normal <5%) Blasts have fine chromatin with 2-4 nucleoli, basophilic cytoplasm with paucity of granules. 4. Dysmegakaryopoiesis : Megakaryocytes are usually reduced in number. Many micro megakaryocytes with mono/bilobate forms are present. 5. Iron Stores : Iron stores are increased because of ineffective erythropoiesis. Ring sideroblasts are the characteristic feature.

16. Bone marrow aspirate showing blasts Blasts seen Blasts with Auer rods Hypercellular marrow

17. 5. Bone marrow biopsy: Micro megakaryocytes are recognized by vesicular nuclei and minimal cytoplasm. Their presence is the characteristic feature of MDS . Megakaryocytic dysplasia and some of the megakaryocytes are seen There is increased angiogenesis and apoptosis in MDS. 6. Differential diagnosis of MDS : The following disease states should be ruled out Vit. B12 and folate deficiency HIV infection Exposure to arsenic Parvo Virus B19 infection

18. CYTOGENETICS IN MDS Clonal cytogenetic abnormalities are found in 80-90% of secondary MDS and 50% of primary MDS cases. Some of the commonly encountered cytogenetic abnormalities are: monosomy 5 del 5q monosomy 7 Loss of Y chromosome Trisomy 11 trisomy8

19. Other diagnostic tests: Immunocytochemistry Immunophenotyping Flow cytometry FISH  (fluorescence in situ hybridization)

20. Treatment: Supportive care with one or more of the following: Transfusion therapy. Erythropoiesis-stimulating agents. Antibiotic therapy. Treatments to slow progression to acute myeloid leukaemia (AML): Lenalidomide. Immunosuppressive therapy. Azacitidine and decitabine. Chemotherapy used in acute myeloid leukaemia. Chemotherapy with stem cell transplant.

21. References Author:- Dr. Tejindar Singh Chapter: - Myelodysplastic syndrome Edition:-3rd Edition Textbook:-Textbook of Hematology Publisher:- APC Year: -January 2016-17

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