Leukemia Lymphoma

1. Dr Chaitanya Vemuri Leukemia & Lymphoma

2. Acute Leukemia

3. DEFINITION Failure of cell maturation Proliferation of immature cells which fill up marrow Ultimately immature cells spill over to peripheral blood

4. Classification of leukemias

5. Leukemia Classification Acute Leukemias: Myeloid - M0, M1, M2, M3, M4, M5, M6, M7 Lymphoid - L1, L2, L3. Chronic Leukemias: Myeloid - CML Lymphoid- CLL, PLL, HCL,

6. Acute Leukemia accumulation of blasts in the marrow

7. AML-M3 - Auer Rods

8. Causes of acute leukemias Idiopathic (most) Underlying hematologic disorders Chemicals , drugs Ionizing radiation Viruses (HTLV I) Hereditary / genetic conditions

9. CLINICAL FEATURES Fever Anemia Thrombocytopenia Bone pain tenderness (Sternal), Migrating joint pains Leukemic infiltration of tissues Hepatosplenomegaly Lymphadenopathy Gum hypertrophy Soft tissues (Chloroma) Intracerebral leukocytostatis (BALL’s disease) (AML) Leukemic meningitis (ALL)

10. Clincal manifestations Symptoms due to: Marrow failure Tissue infiltration Leukostasis Constitutional symptoms Other (DIC) Usually short duration of symptoms

11. Marrow failure Neutropenia : infections, sepsis Anemia : fatigue, pallor Thrombocytopenia : bleeding

12. Infiltration of tissues/organs Enlargement of liver, spleen, lymph nodes Gum hypertrophy Bone pain Other organs: CNS, skin, testis, any organ

13. Gum hypertrophy

14. ALL:Cervical Lymphadenopathy

15. Organomegaly

16. Mediastinal Lymphnodes-ALL

19. LAB INVESTIGATIONS Normocytic / Normochromic Anemia Thrombocytopenia ? Total count (20,000 to 50,000 cells) Peripheral blood smear – Numerous blast cells Marrow – Blast cells > 20% (Nucleated cells) X-Ray chest – Mediastinal widening

20. MANAGEMENT Supportive Anemia – Blood Transfusion Thrombocytopenia – Platelet Transfusion Infection – Blood culture and sensitivity Barrier nursing

21. How to distinguish AML vs CMLfrom looking at peripheral blood Myeloid cell CML AML Normal Blasts q q Promyelocytes q Myelocytes q Metamyelocytes q Bands q Neutrophils q # q

22. AML M1 – Myloblast without maturation (Non granular cytoplasm) M2 – Myloblast with maturation (more mature cells seen) M3 – Hypergranular “Promyelocytic” Leukemia M4 – Myelomonocytic Leukemia – Both Myeloid / Monocyte immature cells M5 – Monocytic Leukemia M6 –Erythroleukemia(Erythroblasts>50%, marrow with immature myeloblasts) M7 – Megakaryoblastic Leukemia (? Megakaryoblasts)

23. ALL L1 – Homogenous small lymphoblasts L2 – Heterogenous Lymphoblasts L3--Homogenous large lymphoblasts

24. POOR PROGNOSTIC FEATURES Increasing age Male sex High leucocyte count at diagnosis CNS involvement at diagnosis Antecedent hematological disorder Cytogenetic abnormalities

27. Chronic Leukemia

28. Chronic Leukemia Chronic - (Long natural history) CML CLL

29. CML Myeloproliferative stem cell disorder Proliferation of all haematopoietic lineages Maturation occurs fairly normally Characterised by presence of Philadelphia (Ph) chromosome

31. Natural History Chronic Phase Accelerated Phase Blast Phase

32. Clinical Features - Symptoms Asymptomatic – 25% Usually presents in chronic phase General weakness Weight loss Dyspnoea (reduced Hb) Abdominal pain, discomfort, fullness (Splenomegaly) Fever, sweats (NOT due to infection) Headache (occasionally) – hyperleucocytosis Bruising, bleeding (uncommon)

33. Clinical Features - Signs Pallor Splenomegaly (often massive) – occasional friction rub Hepatomegaly (50%) Lymphadenopathy – unusual – blast crisis Retinal haemorrhage - leucostasis

34. Investigations CBC Hb – low / Normal WBC – Raised Platelets – Low / Normal / Raised

35. Investigations Peripheral smear Neutrophilia Full range of granulocyte precursors from myeloid to mature neutrophils seen Accelerated phase % of more primitive cells raised Blast phase Dramatic increase in number of circulating blasts

36. Investigations Bone Marrow Increased cellularity, increased myeloid precursors Philadelphia chromosome FISH / RT – PCR For Cytogenetic / Molecular Abnormalities

37. Imatinib Mesylate Hydroxycarbamide Alpha interferon Allogenic bone marrow transplantation BLAST CRISIS : Imatinib / Cytarabine Management

38. CLL Commonest Leukemia Male to female ratio 2 : 1 Median age – 65 to 70 Rise in frequency with advance age Invariably lymphocytic in origin Increased mass of Immuno – incompetent cells accumulate

39. Clinical Features - Symptoms Incidental finding Insidious onset Anemia (Hemolysis / Marrow infiltration) Recurrent infections Functional leukopenia Immune failure (reduced immunoglobins) Painless lymphadenopathy Abdominal pain / discomfort / fullness – Splenomegaly Night sweats / weight loss

40. Clinical Features - Signs Anemia Fever Generalised lymphadenopathy Hepatosplenomegaly

41. Investigations Blood Count Hb – Normal / Low WBC raised Platelet – Normal / Low Peripheral smear Mature lymphocytosis

42. Investigations Bone Marrow Heavy infiltration with lymphocytes For prognosis Immunophenotyping Cytogenetics Prognosis Reticulocyte Count Direct Coombs test Immunoglobins – Low / Normal

44. Management Chlorambucil Alkylating agent Reduced blood count, reduces lymphadenopathy and splenomegaly Fludarabine Purine analogue Corticosteroids

45. Management Supportive Care Anemia / Thrombocytopenia Infections Radiotherapy Lymphnode causing discomfort / obstruction Symptomatic splenomegaly Splenectomy Hypersplenism / Autoimmune destruction Massive splenomegaly

46. Lymphoma

47. What is lymphoma ? Neoplasms of lymphoid origin, typically causing lymphadenopathy

48. Introduction: Neoplastic lymphoid proliferation Fever, lymphadenopathy. Firm rubbery lymphnodes – painless Immune disorders - Deficiency/ autoimmune Rare metastasis out of RES. Two types – Hodgkins & Non-Hodgkins. Viral, genetic, unknown etiology. Lack of programmed cell death - Apoptosis

49. Lymphoma classification(based on 2001 WHO) B-cell neoplasms Precursor B-cell neoplasms (2 types) Mature B-cell neoplasms (19) B-cell proliferations of uncertain malignant potential (2) T-cell & NK-cell neoplasms Precursor T-cell neoplasms (3) Mature T-cell and NK-cell neoplasms (14) T-cell proliferation of uncertain malignant potential (1) Hodgkin lymphoma Classical Hodgkin lymphomas (4) Nodular lymphocyte predominant Hodgkin lymphoma (1)

50. Hodgkin lymphoma

51. Epidemiology less frequent than non-Hodgkin lymphoma overall M > F, 1.5 : 1 Median age – 31 years, 1st peak at 20 -35 years, 2nd peak at 50 – 70 years Etiology unknown Link to EBV doubtful (IMN)

52. Hodgkin lymphoma Cell of origin: germinal centre B-cell Reed-Sternberg cells (or RS variants) – large malignant binucleate lymphoid cells of B cell origin – histological hallmark Most cells in affected lymph node are polyclonal reactive lymphoid cells, not neoplastic cells

53. Reed-Sternberg cell

54. Clinical manifestations: Painless, Rubbery lymphadenopathy contiguous spread Fever, Eosinophilia Hepatosplenomegaly extranodal sites (bone, brain, skin) relatively uncommon except in advanced disease

55. Skin involvement as a late complication in 10% Constitutional symptoms: fever (Pel-Epstein), pruritus, alcohol-induced pain in widespread disease Diagnosis confirmed by histopathology of node

56. Staging of lymphoma

57. CBC, ESR RFT, LFT LDH Chest X-ray Bone marrow trephine biopsy Abdominal and chest CT scan - staging Lymphnode biopsy Staging laparotomy - often not required Investigations

58. RT: Stage I, IIA with < 3 areas, post CT, pressure symptoms Chemotherapy: B symptoms, IIA with > 3 areas, III & IV Chlorambucil, Vinblastin, Procarbazine, Prednisolone (ChVPP) Combined : bulky disease, CT followed by RT Permanent infertility, premature menopause, AVN, myelodysplasia, a/c leukemia Treatment

59. Non-Hodgkin lymphomaIncidence

60. Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents – HTLV 1, EBV, H.Pylori ionizing radiation Genetics : t (14 : 18) – follicular NHL

61. Clinical manifestations Variable severity: asymptomatic to extremely ill time course: evolution over weeks, months, or years Systemic manifestations Widely disseminated at presentation fever, night sweats, weight loss, anorexia, pruritis Extra nodular disease more common (BM, gut, thyroid, lung, skin, testis, brain, Bone) Local manifestations lymphadenopathy, splenomegaly most common any tissue potentially can be infiltrated

62. Complications of lymphoma bone marrow failure (infiltration) CNS infiltration immune hemolysis or thrombocytopenia compression of structures (eg spinal cord, SVC, IVC ) by bulky disease pleural/pericardial effusions, ascites

63. Clinical Staging of NHL Same as HL Extranodular disease more common in T cell disease Bone marrow involvement in low grade NHL

64. Laboratory Diagnosis of NHL Haematological: Normocytic normochromic anemia, High ESR Leucocytosis, Eosinophilia, lymphopenia Leukoerythroblastic picture - BM infiltration HIV testing Bone marrow: Normal, or late involvement. Trephine biopsy- diffuse or follicular infiltration Biochemical: High serum LDH – poor prognosis Hypercalcaemia, Alkaline phosphatase, Uric acid. Serum transaminases & Bilirubin – Liver

65. Lymph node or tissue biopsy for evaluation of:

66. Low-grade lymphoma - watch & wait Aggressive lymphoma grows faster, needs treatment as soon as possible Indications for treatment : Systemic symptoms Lymphadenopathy causing discomfort / disfigurement BM failure Compression syndromes Chemotherapy is the mainstay - CHOP RT: for stage I Monoclonal Ab – anti CD 20 Ab – Rituximab (R-CHOP) Autologous SCT Treatment

67. THANK YOU