![Physical Examination
Performance status (prognostic factor)
Ecchymosis and oozing from IV sites (DIC, possible acute promyelocytic leukemia)
Fever and tachycardia (signs of infection)
Papilledema, retinal infiltrates, cranial nerve abnormalities (CNS leukemia)
Poor dentition, dental abscesses
Gum hypertrophy (leukemic infiltration, most common in monocytic leukemia)
Skin infiltration or nodules (leukemia infiltration, most common in monocytic leukemia)
Lymphadenopathy, splenomegaly, hepatomegaly
Back pain, lower extremity weakness [spinal granulocytic sarcoma, most likely in t(8;21)
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Moeez
- 1.
- 2. Dr. Moeez Qaiser PGR M lll, SHL
- 3. A 22 years old female Yasmin resident of Lahore presented with complaints of : Fever (off and on) 3 months Productive Cough 3 months Shortness of Breath 1 & Half month Presenting Complaints
- 4. Tuberculosis Recurrent Pneumonia Lung abscess Anemia Lymphoproliferative disorders. Malignancy Autoimmune Connective tissue disorders Differential Diagnosis
- 5. Fever was: Gradual in onset Low grade Intermittent More at night Doc. as 100-101 F Relieved only temporarily by anti-pyretics No specific aggravating factors History Of Present illness
- 6. Associated with: Rigors and chills Night sweats Anorexia Weight loss ( 5 Kg over 3 months) Easy fatigueability Generalized body aches/ pains Cough with sputum Pain abdomen off and on Shortness of Breath Fever was Not associated with: • Vomiting • Loose motion • Ear discharge • Dysuria/Burning micturition • Rash/spots on any part of the body • Any mucosal bleed
- 7. Moderate in severity More at night Productive Quarter a cup , odorless Yellowish No hemoptysis Relieved By Cough syp. Cough was
- 8. Gradual in onset Progressive Aggravated by exertion Associated with: Palpitations Productive cough Not Associated with: Orthopnea Paroxysmal nocturnal dyspnea Chest pain Shortness of breath:
- 9. H/O: 2-3 blood transfusions TB contact – Father No H/O: Smoking IV drug abuse Asthma Animal contact Any foreign travel No H/O joint pains No H/O any S.Abortion
- 10. Occupational History: Housewife No h/o any radiation exposure Family history: Mother – Diabetic Father – TB (5 yrs back) – Took ATT(9 Mo) Menstrual History: Age of Menarche : 13 yrs 30/5 cycle , Regular History:
- 11. Surgical History C-Section – 2 times Drug History: Antipyretics (Panadol) Antitussives Antibiotics ATT (5 days) then quit
- 12. Tuberculosis Recurrent Pneumonia Anemia Lymphoproliferative disorders. Malignancy Differential Diagnosis
- 13. An ill looking young female with average built oriented in time, place and person with following vitals: Pulse: 102/min Regular B.P: 110/70 R/R: 20/min Temp: 99 F0 Examination:
- 14. Pallor++ Clubbing 0 Cyanosis 0 Jaundice 0 Pedal oedema 0 A single anterior cervical lymph node palpable B/L Axillary and Inguinal lymph nodes were not palpable Lymph nodes were non-tender, rubbery in consistency, not attached to overlying skin, having no discharge or sinuses.
- 15. No significant abnormal findings found in Respiratory and Cardio- vascular system.
- 16. Abdomen was soft non-tender Liver palpable B/S were audible. GIT
- 17. GCS 15/15 Grossly intact Low mood No focal or neurological deficit CNS
- 18. A 22 year old female presented with 3 months h/o fever, productive cough and progressive shortness of breath associated with pallor, lymph-adenopathy and Hepatomegaly .. Summary
- 19. Lymph proliferative disease Tuberculosis Differential Diagnosis:
- 20. Investigation
- 21. HGB – 4.6 gm/dl WBC - 6.6 , N:74% L:20% M:5% E:1% Platelets – 39 HCT - 15 MCV – 85% ESR – 160 CBC
- 22. Blast cells 55% Myelocytes 30% Neutrophils 21% Lymphocytes 20% Monocytes 1% Retic count 1.4% Peripheral Smear
- 23. LFTS – Normal RFTS – Normal S/E – Normal Coagulation Profile – PT :13 INR : 1.4 APTT : 33 Urine C/E – Normal
- 24. Malarial Parasite Slide : -ve Blood Culture & Sensitivity : awaited Sputum For AFB : -ve
- 25. Serum Iron : 41ug/dl TIBC : 175% Transferrin sat . : 23.4% LDH – 270 U/L Uric Acid – 3.9 Viral Serology –ve Fecal occult blood –ve
- 26. CXR - Normal USG – Liver size 18cm Spleen size 10cm
- 29. Lymph node Biopsy report awaited
- 30. AML ( Acute Myeloid leukemia ) Final Diagnosis
- 31. Decision about treatment depends on clinical stage, prognostic factors and patient condition Treatment
- 32. During her stay After the reports, the nature of illness, treatment options and prognosis was explained. Discharged and refered to Oncologist
- 34. Epidemiology Incidence -3.5 per 100,000 people per year Median age at diagnosis- 67 years AML incidence increases with age
- 36. Etiology Heredity Down syndrome Fanconi anemia Bloom syndrome ataxia-telangiectasia Congenital neutropenia (Kostmann syndrome) Radiation High-dose radiation (atomic bombs survivors)
- 37. chemical and occupational exposures Benzene petroleum products Paint embalming fluids ethylene oxide Herbicides smoking
- 38. Drugs Alkylating agent Topoisomerase II inhibitor Chloramphenicol Phenylbutazone Chloroquine methoxypsoralen
- 39. Clinical Presentation Nonspecific symptoms Fatigue Anorexia Weight loss Fever Bleeding, easy bruising Bone pain, lymphadenopathy, nonspecific cough, headache, or diaphoresis
- 40. Physical Findings Fever Splenomegaly Hepatomegaly Lymphadenopathy Sternal tenderness Evidence of infection and hemorrhage
- 41. Gum hypertrophy
- 42. Diagnostic procedure Morphology cytochemistry Immunophenotyping Cytogenetics Molecular cytogenetics Molecular genetics
- 45. Bone marrow in acute leukemia Necessary for diagnosis Useful for determining type Useful for prognosis Acute leukemias are defined by the presence of > 20% blasts in bone marrow (% of nucleated marrow cells)
- 46. Auer rods in AML
- 47. Pretreatment EvaluationInitial Diagnostic Evaluation and Management of Adult Patients with AML History Increasing fatigue or decreased exercise tolerance (anemia) Excess bleeding or bleeding from unusual sites (DIC, thrombocytopenia) Fevers or recurrent infections (granulocytopenia) Headache, vision changes, nonfocal neurologic abnormalities (CNS leukemia or bleed) Early satiety (splenomegaly) Family history of AML (Fanconi, Bloom, or Kostmann syndromes or ataxia-telangiectasia) History of cancer (exposure to alkylating agents, radiation, topoisomerase II inhibitors) Occupational exposures (radiation, benzene, petroleum products, paint, smoking, pesticides
- 48. Physical Examination Performance status (prognostic factor) Ecchymosis and oozing from IV sites (DIC, possible acute promyelocytic leukemia) Fever and tachycardia (signs of infection) Papilledema, retinal infiltrates, cranial nerve abnormalities (CNS leukemia) Poor dentition, dental abscesses Gum hypertrophy (leukemic infiltration, most common in monocytic leukemia) Skin infiltration or nodules (leukemia infiltration, most common in monocytic leukemia) Lymphadenopathy, splenomegaly, hepatomegaly Back pain, lower extremity weakness [spinal granulocytic sarcoma, most likely in t(8;21) patients]
- 49. Initial Diagnostic Evaluation and Management of Adult Patients with AML Laboratory and Radiologic Studies CBC with manual differential cell count Chemistry tests (electrolytes, creatinine, BUN, calcium, phosphorus, uric acid, hepatic enzymes, bilirubin, LDH, amylase, lipase) Clotting studies (prothrombin time, partial thromboplastin time, fibrinogen, D-dimer) Viral serologies (CMV, HSV-1, varicella-zoster) RBC type and screen HLA typing for potential allogeneic HSCT Bone marrow aspirate and biopsy (morphology, cytogenetics, flow cytometry, molecular studies for NPM1 and CEBPA mutations and FLT3-ITD) Cryopreservation of viable leukemia cells Echocardiogram or heart scan PA and lateral chest radiograph Placement of central venous access device
- 50. Initial Diagnostic Evaluation and Management of Adult Patients with AML Interventions for Specific Patients Dental evaluation (for those with poor dentition) Lumbar puncture (for those with symptoms of CNS involvement) Screening spine MRI (for patients with back pain, lower extremity weakness, paresthesias) Social work referral for patient and family psychosocial support Counseling for All Patients Provide patient with information regarding their disease, financial counseling, and support group contacts.
- 51. Prognostic Factors Age at diagnosis Chronic and intercurrent diseases Performance status A prolonged symptomatic interval with cytopenias preceding diagnosis A high presenting leukocyte count Chromosome findings at diagnosis* Achievement of CR Secondary AML
- 52. Principles of treatment Combination chemotherapy First goal is complete remission Further rx to prevent relapse Supportive medical care Transfusions, antibiotics, nutrition Psychosocial support Patient and family
- 53. Complete remission CR is defined- Blood neutrophil count -1000/L Platelet count 100,000/L. Circulating blasts - absent. The bone marrow <5% blasts Auer rods -absent. Extramedullary leukemia -absent
- 55. Induction Chemotherapy Cytarabine is usually administered as a continuous intravenous infusion for 7 days Anthracycline therapy generally consists of daunorubicin intravenously on days 1, 2, and 3 (the 7 and 3 regimen). Etoposide
- 56. Postremission Therapy Postremission therapy is designed to eradicate residual leukemic cells to prevent relapse and prolong survival
- 57. Intensive chemotherapy High-dose cytarabine 4 cycles of HiDAC (3 g/m2 per q12h on days 1, 3, and 5) Allogeneic or autologous HSCT
- 58. Patients who fail to attain CR after two induction courses should be treated with an allogeneic hematopoietic stem cell transplant (HSCT)
- 59. Hematopoietic stem cell transplantation • Permits “rescue” from otherwise excessively toxic treatment • Additional advantage of graft-vs-leukemia effect in allogeneic transplants • Trade-off for allogeneic transplantation: greater anti-leukemic effect but more toxic
- 60. Management of special situations
- 61. Hyperleukocytosis • Hyperleukocytosis with leukostasis immediate medical treatment. • Leukapheresis • Hydroxyurea, given at dosages up – 50 to 60 mg/kg per day. – Until the wbc has been reduced. • Prevention of tumor lysis syndrome – Hydration, – Control of uric acid production using allopurinol or rasburicase – Control of urine ph
- 62. CNS involvement • Less than 5% of patient • Intrathecal cytarabine • Dexamethasone to prevent arachnoiditis
- 63. Supportive Care
- 64. Prophylactic anti-infectious treatment • Personal hygiene • Dental hygiene • Vigorous hand washing • Anti-fungal prophylaxis • Antibiotic prophylaxis Leibovici L, Paul M, Cullen M, et al. prophylaxis in neutropenic patients. New evidence, practical decisions.Cancer.2006;107(8):1743-1751.
- 65. Transfusion support • Prophylactic platelet transfusions- • hemoglobin level above 8 g/dL • Prevent alloimmunization • Gamma irradiation (at least 25 Gy) Schiffer CA, Anderson KC, Bennett CL, et al. transfusion for patients with cancer: clini-cal practice guidelines of the American Clinical Oncology.J Clin Oncol.2001;19(5):1519-1538.
- 66. Selected New Agents under Study for the Treatment of Adults with AML Class of Drugs Examples of Agents in Class Tyrosine kinase inhibitors PKC412, MLN518, SU11248, CHIR-258, imatinib (STI571, Gleevec), dasatinib, AMN107 Demethylating agents Decitabine, 5-azacytidine Histone deacetylase inhibitors Suberoylanilide hydroxamic acid (SAHA), MS275, LBH589, valproic acid Heavy metals Arsenic trioxide Farnesyl transferase inhibitors R115777, SCH66336 HSP-90 antagonists 17-allylaminogeldanamycin (17-AAG), DMAG, or derivatives Cell cycle inhibitors Flavopiridol, CYC202 (R-Roscovitine), SNS-032 Toxin-conjugated antibodies Gemtuzumab ozogamicin Proteasome inhibitors Bortezomib Aurora inhibitors AZD1152, MLN-8237, AT9283 Immunomodulatory Lenalidomide, IL-2, histamine dihydrochloride