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Acute Leukemia Rakesh Biswas MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India.

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Presentation on theme: "Acute Leukemia Rakesh Biswas MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India."— Presentation transcript:

1 Acute Leukemia Rakesh Biswas MD, Professor, Department of Medicine, People's College of Medical Sciences, Bhanpur, Bhopal, India

2 A 16 year old girl Extreme pallor gum bleeds, Purpura,With Lymphadenopathy and Hepatosplenomegaly

3 Possible causes: Investigations and treatment

4 Only a week later, D was ill again, with a fever, severe headache, and extreme lethargy.

5 During a sunny spring weekend, D would go outside to play, only to return minutes later exhausted, flopping herself onto the sofa to rest

6 Leukemia Group of malignant disorders of the hematopoietic tissues characteristically associated with increased numbers of white cells in the bone marrow and / or peripheral blood

7 Once inside the van and on our way out of the clinic parking lot, she asked, "Dad, what is leukemia?" "Can I die from this?"

8 Classification Classified based on cell type involved and the clinical course Classified based on cell type involved and the clinical course 1. Acute : 1. Acute : ALL ALL AML AML 2. Chronic : CLL CLL CML CML

9 Subclassification ALL ALL Common type( pre-B) Common type( pre-B) B-cell B-cell T-cell T-cell Undifferentiated Undifferentiated

10 After the oncologist performed a bone marrow aspiration to confirm the diagnosis of leukemia, we learned specifically what type it was and the count. "D had acute lymphoblastic leukemia, early pre-B cell.

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13 Myelomono

14 AML French-American-British (FAB) Classification M0: Minimally differentiated leukemia M1: Myeloblastic leukemia without maturation M2: Myeloblastic leukemia with maturation M3: Hypergranular promyelocytic leukemia M4Eo: Variant: Increase in abnormal marrow eosinophils M4: Myelomonocytic leukemia M5: Monocytic leukemia M6: Erythroleukemia (DiGuglielmo's disease) M7: Megakaryoblastic leukemia Ref-Harrison’s Principle of Internal Medicine

15 CLL CLL B-cell: common B-cell: common T-cell: rare T-cell: rare

16 CML CML Ph +ve Ph +ve Ph –ve, BCR-abl +ve Ph –ve, BCR-abl +ve Ph –ve, BCR-abl -ve Ph –ve, BCR-abl -ve Eosinophilic Leukemia Eosinophilic Leukemia Ph: Philadelphia chromosome Ph: Philadelphia chromosome BCR: Breakpoint cluster region; abl : Abelson oncogene BCR: Breakpoint cluster region; abl : Abelson oncogene

17 Acute Myeloid Leukemia ( AML) Malignant transformation of a myeloid precursor cell ; usually occurs at a very early stage of myeloid development Malignant transformation of a myeloid precursor cell ; usually occurs at a very early stage of myeloid development Rare in childhood & incidence increases with age Rare in childhood & incidence increases with age

18 Etiology Unknown / De-novo !! In majority Predisposing factors: Ionizing radiation exposure Ionizing radiation exposure Previous chemotherapy : alkylating agents Previous chemotherapy : alkylating agents Occupational chemical exposure : benzene Occupational chemical exposure : benzene Genetic factors: Down’s Syndrome, Bloom’s, Fanconi’s Anemia Genetic factors: Down’s Syndrome, Bloom’s, Fanconi’s Anemia Viral infection ( HTLV-1) Viral infection ( HTLV-1) Immunological : hypogammaglobulinemia Immunological : hypogammaglobulinemia Acquired hematological condition -Secondary Acquired hematological condition -Secondary

19 Epidemiology M > F M > F ALL which predominantly affects younger individuals ALL which predominantly affects younger individuals AML – adults and the elderly AML – adults and the elderly Median age gp-65yrs Median age gp-65yrs Geographical variation-none Geographical variation-none

20 Clinical features General : Onset is abrupt & stormy General : Onset is abrupt & stormy (usually present within 3 months) (usually present within 3 months) Bone marrow failure (anemia, infection,bleeding) Bone marrow failure (anemia, infection,bleeding) Bone pain & tenderness Bone pain & tenderness

21 Specific: M2 : Chloroma:-presents as a mass lesion ‘tumor of leukemic cells’ M2 : Chloroma:-presents as a mass lesion ‘tumor of leukemic cells’ M3 : DIC M3 : DIC M4/M5 : Infiltration of soft tissues, gum infiltration, skin deposits,Meningeal involvement-headache, vomiting, eye symptoms M4/M5 : Infiltration of soft tissues, gum infiltration, skin deposits,Meningeal involvement-headache, vomiting, eye symptoms

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23 Skin Infiltration with AML (Leukemia Cutis)

24 Diagnosis Blood count : WBC usually elevated (50,000- 1,00,000 / cmm ); may be normal or low; often anemia & thrombocytopenia Blood count : WBC usually elevated (50,000- 1,00,000 / cmm ); may be normal or low; often anemia & thrombocytopenia Blood film : (as above) Blast cells Blood film : (as above) Blast cells

25 P. Smear AML

26 Bone marrow aspirate & trephine: Hypercellular, Bone marrow aspirate & trephine: Hypercellular, blast cells ( > 20%), blast cells ( > 20%), presence of Auer rods - AML type presence of Auer rods - AML type Cytochemistry : Special stains to differentiate AML from ALL ; Positivity with Sudan black & Myeloperoxidase (MPO) in AML Cytochemistry : Special stains to differentiate AML from ALL ; Positivity with Sudan black & Myeloperoxidase (MPO) in AML

27 Jemshidi trephine & Salah aspiration needle

28 Auer Rods in Leukemia cells

29 MPO (right) & Sudan black (left) showing intense localised positivity in blasts

30 Confirmation: Confirmation: Immunophenotyping Immunophenotyping Molecular genetics Molecular genetics Cytogenetics: Chromosomal abnormalities Cytogenetics: Chromosomal abnormalities

31 Other Inv : Coagulation screen, fibrinogen, D- dimer Coagulation screen, fibrinogen, D- dimer RFT, LFT RFT, LFT LDH, Uric acid LDH, Uric acid Urine Urine CXR CXR ECG, ECHO ECG, ECHO

32 Management I. Supportive care : I. Supportive care : Anemia – red cell transfusion Anemia – red cell transfusion Thrombocytopenia – platelet concentrates Thrombocytopenia – platelet concentrates Infection – broad spectrum IV antibiotics Infection – broad spectrum IV antibiotics Hematopoietic growth factors : GM-CSF, G-CSF Hematopoietic growth factors : GM-CSF, G-CSF Barrier nursing Barrier nursing Indwelling central venous catheter Indwelling central venous catheter

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34 Metabolic problems : Monitoring hepatic / renal / hematologic function; Fluid & electrolyte balance, nutrition Hyperuricemia- hydration, Allopurinol Metabolic problems : Monitoring hepatic / renal / hematologic function; Fluid & electrolyte balance, nutrition Hyperuricemia- hydration, Allopurinol Psychological support Psychological support

35 The white blood cell count in her peripheral blood was about 550,000. Her bone marrow was packed with leukemia blasts."

36 The next thing that occurred was a procedure called leukopheresis. This procedure lasted 4 hours and cut D’s white blood cell (WBC) count in half--to about 250,000.

37 She was administered chemotherapy immediately following the leukopheresis procedure. The next day we learned that the chemo had produced an effect as well: The WBC had halved again--125,000.

38 SPECIFIC THERAPHY: Chemotherapy : Induction: (4-6 wks) vincristine, prednisone, anthracycline, (idarubicin or daunorubicin) cyclophosphamide, and L-asparaginase

39 Consolidation: (multiple cycles of intensive chemotherapy given over a 6 to 9 month period). Cytosine arabinoside, high-dose methotrexate, etoposide anthracycline, (idarubicin or daunorubicin)

40 Maintenance phase: (18 to 24 months). LPs with intrathecal MTX every 3 months, Monthly vincristine, Daily 6-MP, and weekly MTX.

41 At day 29 of the induction protocol D was declared to be in complete remission. We were all relieved with this news.

42 Step two was the next phase of treatment called consolidation therapy. This entailed multiple combinations of drugs administered on a rotational basis (on various weeks) for the next six months.

43 For instance, she would receive an infusion of methotrexate for a couple of days and then take 6- MP by mouth for a week. Another cycle included VM-26 (Teniposide) and Ara-C.

44 Complete remission ( CR): < 5% blast cells in normocellular bone marrow Complete remission ( CR): < 5% blast cells in normocellular bone marrow Autologous BMT : Can be curative in younger patient (< yrs) Autologous BMT : Can be curative in younger patient (< yrs)

45 Exactly 5 months since her diagnosis, and 16 weeks of remission… "We're at the clinic. D has relapsed. Her white count is 27,000."

46 The Consolidation protocol had been dropped and replaced with a new induction protocol. After the bone marrow aspiration to determine the extent of the leukemia relapse, she was given doxirubicin, vincristine and L-asparaginase.

47 For several days following D‘s discharge from the bone marrow transplant unit, all of us loaf around the house and recuperate from our 90 day marathon…

48 …the first 30 days representing Ds' relapse and the induction therapy to obtain a second remission

49 Back in fighting form, D proceeds directly to the final 30 days of the marathon--the actual bone marrow transplant. BMT patients are in a delicate condition following discharge

50 Looking back, the nine weeks or so--the post BMT discharge period--was a sublime time for us. D was home and was feeling pretty good.

51 As D’s hair began to grow again, we rubbed her head every night at the dinner table, wondering what color it was going to be or if it was going to be curly or straight. We never found out.

52 On Monday, March 1, 1999 we went to clinic and waited for the lab results. The results came back as we feared. D had relapsed. Her white count was 47,000. We were devastated.

53 III. PALLIATIVE THERAPHY III. PALLIATIVE THERAPHY Chemo, RT, Blood product support Chemo, RT, Blood product support

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55 Prognosis Median survival without treatment is 5 weeks Median survival without treatment is 5 weeks 30% 5-yr survival in younger patients with chemotherapy 30% 5-yr survival in younger patients with chemotherapy Disease which relapses during treatment or soon after the end of treatment has a poor prognosis Disease which relapses during treatment or soon after the end of treatment has a poor prognosis

56 Poor prognostic factors Increasing age Increasing age Male sex Male sex High WBC count at diagnosis High WBC count at diagnosis CNS involvement at diagnosis CNS involvement at diagnosis Cytogenetic abnormalities Cytogenetic abnormalities Antecedent hematological abnormalities (eg. MDS) Antecedent hematological abnormalities (eg. MDS) No complete remission No complete remission

57 Two things that I will always remember about D: She was a collector of many things, trinket boxes, key rings. But she was first and foremost a collector of "FRIENDS."

58 Among other things, she wrote: "Hair loss is a side effect of chemotherapy, and cancer is a side effect of life."

59 Summary; Learning Points

60 THANK YOU THANK YOU


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