History
• General Data– Patient is RB, 30/F from Pandacan, Manila,
Jehovah’s Witness, nonsmoker, non-alcoholic beverage drinker, nonasthmatic, nondiabetic, nonhypertensive
• Chief complaint– Gum bleeding
• History of present illness– 5 months prior to admission: Px noted recurrent
hematoma and ecchymoses on her upper extremities. These would disappear spontaneously after 2 to 3 weeks. No consults/meds taken.
– 4 months PTA: Px consulted at PGH OPD and her CBC showed a decreased platelet count. She was on regular follow-up at the OPD and was eventually referred to hematology.
– 3 months PTA: She was seen at the hematology OPD where she was given prednisone 20mg PO to be taken 3 times in the morning and 2 times during the evening. Bone marrow aspiration was also done.
– 2 months PTA: BMA results showed AML. Prednisone was gradually tapered then discontinued last January 6, 2010. Px is on regular ff-up c/o hematology OPD. Px had no signs and symptoms of bleeding but still with low platelet count.
– 2 months PTA (Feb. 14, 2010): Px had epistaxis and gum bleeding and was rushed to the ER. She was eventually admitted at the ward and discharged 10 days later until
– 9 days PTA: She was on her scheduled consult at the Cancer Institute when her CBC showed a platelet count of 20. She was then referred to the ER for low platelet and presence of gum bleeding and was admitted at the ward 2 days later.
Review of systems
• (-) difficulty breathing• (-) fever• (+) easy fatigability• (-) epistaxis • (-) melena• (-) hemarthrosis• (-) hematuria• (-) hematochezia
• Past Medical History– No history of goiter, heart problem, liver problem,
kidney problem, allergy
• Family Medical History– Non-contributory
• OB/Gyne History– G5P5 (5005): 1st 4 children via SVD, youngest via
cesarean section for breech presentation– No fetomaternal complications– Regular monthly menses, lasting 3-4days,
consuming 3 pads/day, (-) dysmenorrhea– (+) OCP use (2006-2008)– (-) IUD/BTL use
• Personal/Social History– Px works as a housewife. Her husband works as a
mechanic. They live with her brother-in-law and his family. All children stopped going to school starting this year.
– No vices, denies exposure to toxins/secondhand smoke
Physical Examination
• General Survey: awake, conversant, not in cardiorespiratory distress
• Vital signs: BP 90/60, HR 92 bpm, RR 18/min, temp 36.8
• HEENT: pale conjunctivae, anicteric sclerae, (-) CLAD, (+) TPC, (-) gum bleeding, (-) epistaxis
• Chest/lungs: equal chest expansion, clear breath sounds, (-) rales, (-) rhonchi, (-) wheezes, adynamic precordium, distinct heart sounds
• Normal rate, regular rhythm, no murmurs• Abdomen: flat, normoactive bowel sounds,
soft, (+) slight epigastic tenderness on deep palpation, (-) guarding, (-) masses, (-) organomegaly
• Skin/extremities: pale nailbeds, full and equal pulses, (-) cyanosis, (-) edema, (-) jaundice, (+) multiple erythematous macules on bilateral lower extremities
Course in the ER and Wards
• February 26, 2010: Px was at Cancer Institute and OPD for her regular check-up. Her CBC showed Hb 94, hct 0.28, plt 20, and WBC 36.7. She was immediately referred to the ER for admission due to her low plt and (+) gum bleeding.
• February 27, 2010: Px was seen by Hematology Service. BT of platelet concentrate was ordered.
• February 28, 2010: Px was seen by the Day MHAPOD. BT of 6 ‘u’ PC and tranexamic acid 500mg cap q8 was ordered. Px was admitted at Ward 1.
• March 2, 2010: s/p BT of 4 ‘u’ PC. Px still had gum bleeding. Additional 6 ‘u’ PC was ordered. CBC showed Hb 90, hct 0.267, plt 10, WBC 37.6, RBC 2.64, blast 0.73. Px also complained of epigastric pain. She was given omeprazole 20 mg/tab OD and ribamipide 100mg TID.
• March 3, 2010: s/p BT 4 ‘u’ PC. Px still has gum bleeding. For transfusion again of 6 ‘u’ PC. Px noted decrease in epigastric pain.
• March 5, 2010: s/p BT 5 ‘u’ PC. Px had fever and chills but no cough, abdominal pain, dysuria, or pallor. Post BT CBC showed Hb 80, hct 0.232, plt 21, WBC 40.1, RBC 2.32, blast 0.77, band/stab 0.01, promyelocyte 0.08. For BT of 6 more ‘u’ PC.
• March 6, 2010: Px had no more fever, active bleeding, cough, and colds. On PE, (+) tonsillar walls congested with exudates. A> ATP. Px was given cefuroxime 750mg IV q8 and paracetamol 500mg/tab q4. UA and CXR were ordered.
• March 7, 2010: s/p BT 6 ‘u’ PC. Px had no new subjective complaints. Still with tonsillopharyngeal wall congestion. Present management continued.
Acute Myelogenous Leukemia
• Malignant bone marrow disease• Hematopoietic precursors arrested in an early
stage of development through activation of abnormal genes through chromosomal translocations and genetic abnormalities
• More common in men and in whites, affecting all age groups
Risk Factors:
• Antecedent hematologic disorder• Congenital syndrome• Heredity• Environmental exposure– Radiation, smoking, benzene
• Exposure to chemotherapeutic agents– Alkylating agents aberrancy in chromosomes 5 & 7
– topoisomerase-II-inhibitors aberrancy in 11q23
I. AML with recurrent genetic abnormalitiesAML with t(8;21)(q22;q22);RUNX1/RUNX1T1b x
AML with abnormal bone marrow eosinophils [inv(16)(p13q22) or t(16;16)(p13;q22);CBFB/MYH11]b
Acute promyelocytic leukemia [AML with t(15;17)(q22;q12) (PML/RAR) and variants]b
AML with 11q23 (MLL) abnormalities
II. AML with multilienage dysplasiaFollowing a myelodysplastic syndrome or myelodysplastic syndrome/myeloproliferative disorder
Without antecedent myelodysplastic syndrome
III. AML and myelodysplastic syndromes, therapy-relatedAlkylating agent–related
Topoisomerase type II inhibitor–related
Other types
IV. AML not otherwise categorizedAML minimally differentiated Acute erythroid leukemia
AML without maturation Acute megakaryoblastic leukemia
AML with maturation Acute basophilic leukemia
Acute myelomonocytic leukemia Acute panmyelosis with myelofibrosis
Acute monoblastic and monocytic leukemia Myeloid sarcoma
French-American British (FAB) Classification
FAB Classification Incidence (%)
M0: Minimally differentiated leukemia 50
M1: Myeloblastic leukemia without maturation 30
M2: Myeloblastic leukemia with maturation 20
M3: Hypergranular promyelocytic leukemia 10
M4: Myelomonocytic leukemia 20
M4Eo: Variant: Increase in abnormal marrow eosinophils
M5: Monocytic leukemia 10
M6: Erythroleukemia (DiGuglielmo's disease) 4
M6: Erythroleukemia (DiGuglielmo's disease) 1
Symptomatology• Nonspecific, beginning gradually or abruptly
and often related to anemia, thrombocytopenia, leukocytosis or leukopenia:– Fatigue– Exertional dyspnea– Dizziness– Anginal pain– Fever with or without infection– Bleeding/easy bruising
Symptomatology
• Symptoms from organ infiltration by leukemic cells:– Early satiety– Gingivitis– Respiratory distress– Altered mental status– Bone pains
Physical Findings
• Fever• Splenomegaly• Hepatomegaly• Lymphadenopathy• Sternal tenderness• Bleeding• Signs of infiltration of gums, skin, soft tissues,
meninges
Hematologic Findings
• Anemia• Leukocytosis, leukopenia, or normal WBC
count• Presence of Auer rods• Thrombocytopenia
Auer Rods
-clumps of rod-shaped azurophilic granular material seen in the cytoplasm of leukemic blasts-composed of fused lysosomes and contain peroxidase, lysosomal enzymes, and large crystalliine inclusionsWhen present, myeloid lineage is certain
Diagnostics
• CBC– Leukocytosis– May also present as thrombocytopenia, anemia or
leukopenia
• Peripheral blood smear– Confirms CBC findings– Presence of circulating blasts
Diagnostics
• Blood chemistry profile– Usually with elevated LDH and uric acid levels
• Bone marrow aspirate and biopsy– > 20% blasts; Auer rods– Evalueates degree of dysplasia
• Immunophenotyping (Flow cytometry)– Distinguish AML from ALL– Further classify into subtypes
Therapeutics
• Chemotherapy as the primary treatment1. Induction Phase2. Postremission Phase
• Supportive care
Induction Chemotherapy
• Often combination therapy with cytarabine and anthracycline (7 and 3 regimen)– Cytarabine: continuous IV infusion for 7 days– Daunorubicin IV on days 1, 2, and 3
• Check BM after induction– if > 5% blasts exist with > 20% cellularity re-
treat or change the therapy
• Allogeneic SCT recommended after two failed induction courses
Supportive Care
• Recombinant hematopoietic factors• Platelet transfusions• pRBC transfusion• Early initiation of empiric antibacterial and
antifungal antibiotics
Postremission Therapy
• To eradicate residual leukemic cellsto prevent relapse and prolong survival
• High-dose cytarabine (3 g/m2 every 12h on D1,3, and 5) effective than standard dose (100 mg/m2 per day for 5 days by continuous infusion)
• Allogeneic SCT used in patients <70 years and with HLA-compatible donor
Relapse• Patients eligible for allogeneic SCT should receive
transplant at the first sign of relapse• Poor outcome of early relapse patients (<12 months)• Patients with longer first CR (>12 months) have
higher chance of attaining CR but cure is uncommon• For elderly patients (>70years) –antibody-targeted
chemotherapy (gemtuzumab ozogamicin) has a CR rate of ~30%
• Consider exploring novel approaches
Agents under Study for AML Treatment in Adults
Class of Drugs Example AgentsMDR1 modulators Cyclosporine, LY335979
Demethylating agents Decitabine, 5-azacytidine, zebularine
Histone deacetylase inhibitors Suberoylanilide hydroxamic acid (SAHA), MS275, LBH589, valproic acid
Heavy metals Arsenic trioxide, antimony
Farnesyl transferase inhibitors R115777, SCH66336
FLT3 inhibitors SU11248, PKC412, MLN518, CHIR-258
HSP-90 antagonists 17-allylaminogeldanamycin (17-AAG) or derivatives
BCR-ABL PDGFR/KIT inhibitors Imatinib (ST1571, Gleevec), dasatinib, nilotinib
Telomerase inhibitor GRN163L
Cell cycle inhibitors Flavopiridol, CYC202 (R-Roscovitine), SNS-032
Nucleoside analogues Clofarabine, troxacitabine
Humanized antibodies Anti-CD33 (SGN33), anti-DR4, anti-DR5, anti-KiR
Toxin-conjugated antibodies Gemtuzumab ozogamicin (Mylotarg)
Radiolabeled antibodies Yttrium-90-labeled human M195