acute myeloid leukemia. case presentation 33 yo filipino male presents with back pain, fevers,...
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Acute Myeloid Acute Myeloid LeukemiaLeukemia
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Case PresentationCase Presentation
33 yo Filipino male presents with 33 yo Filipino male presents with back pain, fevers, weight loss, and back pain, fevers, weight loss, and general malaisegeneral malaise Not felt “normal” in two monthsNot felt “normal” in two months Previously healthyPreviously healthy Sent to NMCSD by PCM for abnormal Sent to NMCSD by PCM for abnormal
labslabs
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PEPE
Mostly unremarkable examMostly unremarkable exam BP: 187/110; HR: 123; T – 98.7; R - 16BP: 187/110; HR: 123; T – 98.7; R - 16 Normal CV/Pulm examNormal CV/Pulm exam No lymphadenapathyNo lymphadenapathy Mild hepatomegaly, no spleenomegalyMild hepatomegaly, no spleenomegaly No ecchymoses or rashNo ecchymoses or rash Mild resting tremorMild resting tremor
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LabsLabs
CBC:CBC: H/H: 14.1/43H/H: 14.1/43 WBC: 11.4WBC: 11.4
Diff: N – 69/Bands - 7/L - 18/M - 10/E - 2Diff: N – 69/Bands - 7/L - 18/M - 10/E - 2 Platelets: 54Platelets: 54 Calcium – 11.0; Phos – 6.9Calcium – 11.0; Phos – 6.9 LDH - 3752LDH - 3752
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AML – The BasicsAML – The Basics AML accounts for 40% AML accounts for 40%
of leukemia cases.of leukemia cases. Approximately 10,000 Approximately 10,000
cases are diagnosed in cases are diagnosed in adults in the US adults in the US annually. annually.
The incidence of AML The incidence of AML increases steadily with increases steadily with increasing age. The increasing age. The median age is 55 to 60. median age is 55 to 60.
Males > females; Males > females; whites > blacks. whites > blacks.
Abeloff: Clinical Oncology, 3rd ed
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AML – The BasicsAML – The Basics
Increased incidence with Down's Increased incidence with Down's syndrome, Bloom's syndrome, syndrome, Bloom's syndrome, Fanconi's anemiaFanconi's anemia
Increased risk with MDS and MPS. Increased risk with MDS and MPS. Multiple environmental risk factors: Multiple environmental risk factors:
exposure to radiationexposure to radiation chemical exposure to benzene, chemical exposure to benzene,
hydrocarbons, and solventshydrocarbons, and solvents treatment with alkylating agentstreatment with alkylating agents
Viruses???Viruses???
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PresentationPresentation
Lethargy, granulocytopenia, and Lethargy, granulocytopenia, and thrombocytopenia are most common. thrombocytopenia are most common.
30% present with a significant skin, soft 30% present with a significant skin, soft tissue, or respiratory infection. tissue, or respiratory infection.
Petechiae with or without bleeding may Petechiae with or without bleeding may be present. be present.
Hyperuricemia is frequent; splenomegaly Hyperuricemia is frequent; splenomegaly is present in about 1/3 of patients. is present in about 1/3 of patients.
Lymphadenopathy and hepatomegaly are Lymphadenopathy and hepatomegaly are uncommon. uncommon.
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Work-upWork-up HistoryHistory
family, work, and family, work, and medical history medical history
radiation and chemical radiation and chemical exposure history exposure history
PhysicalPhysical TemperatureTemperature Cranial nerve exam and Cranial nerve exam and
vision examvision exam Lymph nodes and Lymph nodes and
hepatosplenic exam hepatosplenic exam Special attention to Special attention to
potential sites of potential sites of infectioninfection
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Peripheral SmearPeripheral Smear
Nonspecific Nonspecific findings:findings: Normochromic, Normochromic,
normocytic anemianormocytic anemia ThrombocytopeniaThrombocytopenia Leukopenia (with Leukopenia (with
granulocytopenia)granulocytopenia) May have leukemic May have leukemic
blastsblasts
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DiagnosisDiagnosis
Bone Marrow BiopsyBone Marrow Biopsy Cellularity Cellularity Stains:Stains:
Wright's, Sudan black, esterase stains Wright's, Sudan black, esterase stains Periodic acid-Schiff reagent, iron stain, and Periodic acid-Schiff reagent, iron stain, and
immunofluorescent stainimmunofluorescent stain Aspirate for karyotyping and Aspirate for karyotyping and
immunophenotyping immunophenotyping
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Bone Marrow BiopsyBone Marrow Biopsy
Must have >30% Must have >30% blasts (WHO >20% blasts (WHO >20% blasts)blasts)
Must be myeloid Must be myeloid originorigin
Auer rods found in Auer rods found in most AMLmost AML
http://www.microscopy-uk.org.uk/mag/artaug01/vrcoolpixb.html
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Bone Marrow BiopsyBone Marrow Biopsy
Diagnosis Diagnosis confirmed by confirmed by immunophenotypeimmunophenotype
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http://www.lmp.ualberta.ca/resources/pathoimages/Images-A/000p0360.jpg
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AML -PathologyAML -Pathology
Abnormal clonal proliferation of a Abnormal clonal proliferation of a primitive myloid hematopoietic primitive myloid hematopoietic progenitor cellprogenitor cell
Accumulation in bone marrow Accumulation in bone marrow results in pancytopeniaresults in pancytopenia
Leukemic cells released into Leukemic cells released into circulationcirculation
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Leukemic Cellular OriginLeukemic Cellular Origin
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AML - TypesAML - Types
Classified in the FAB systemClassified in the FAB system Classified using:Classified using:
Morphologic appearance of the blasts Myeloperoxidase stain Sudan black stain Nonspecific esterases Cytogenetic testing Immunologic testing
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TreatmentTreatment
InductionInduction Daunorubicin (3 days) and cytarabine (7 days)
have been used for past 30 years Idarubicin or mitoxantrone may be beneficial
in young patients +/- myeloid growth factor+/- myeloid growth factor
Post Induction TherapyPost Induction Therapy Allogenic bone marrow transplantAllogenic bone marrow transplant Autologous bone marrow transplantAutologous bone marrow transplant ChemotherapyChemotherapy
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TreatmentTreatment
Remission:Remission: Achieved after 7/3 in 70-80% of patients Achieved after 7/3 in 70-80% of patients
under the age of 60under the age of 60 Achieved in 50% of patients older than Achieved in 50% of patients older than
6060 RelapseRelapse
Occurs on average 4 months after Occurs on average 4 months after induction if no further treatmentinduction if no further treatment
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PrognosisPrognosis
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Prognosis after CRPrognosis after CR
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PrognosisPrognosis
Overall for AML:Overall for AML: 70-80% CR70-80% CR 20-30% DFS at 5 years20-30% DFS at 5 years
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Special CasesSpecial Cases
AML M3 (Acute AML M3 (Acute promyelocytic promyelocytic leukemia)leukemia) Induction with all-Induction with all-
trans retinoic acid, trans retinoic acid, followed by followed by ddaunorubicin and cytarabine
High risk of DIC
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Patient PresentationPatient Presentation
Bone Marrow biospyBone Marrow biospy 11stst sample was sample was
fibroticfibrotic 22ndnd sample – AML M7 sample – AML M7
Leukemic cells CD61 Leukemic cells CD61 ++
Negative for other Negative for other stainsstains
Trilineage hypoplasiaTrilineage hypoplasia Extensive bone Extensive bone
marrow necrosismarrow necrosis Stain for CD61 (Glycoprotein IIIa)
http://www.ihcworld.com
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AML M7AML M7 Acute Acute
Megakaryoblastic Megakaryoblastic Leukemia (FAB M7)Leukemia (FAB M7) Accounts for 3-5% of Accounts for 3-5% of
AML (not associated AML (not associated with prior treatment)with prior treatment)
Overall poor prognosisOverall poor prognosis Down Syndrome Down Syndrome
increases riskincreases risk Commonly presents Commonly presents
with a dry bone with a dry bone marrow aspiratemarrow aspirate
Few large studiesFew large studies
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DiagnosisDiagnosis
Anti glycoprotein IIb/IIIa (CD41a)
Platelet peroxidase by electron microscope
Immuno-cytochemistry stain for factor VIII
From http://www.ehatol.org
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AML M7AML M7
Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience From Blood, 2000 Followed 20 study patients with AML M7 1.2% of all new AML cases during study
period Median age: 42.5 70% male predominance (14/20 cases)
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Study TreatmentsStudy Treatments
Patients enrolled in 5 different Patients enrolled in 5 different studiesstudies Different doses Different doses daunorubicin and
cytarabine Other agents added: 6-thiogranine,
idarubicin, GM-CSF Consolidation with chemo or transplant
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AML: the ECOG experience
Outcomes:Outcomes: 50% CR rates50% CR rates Medial remission: 10.6 monthsMedial remission: 10.6 months Median survival: 10.3 monthsMedian survival: 10.3 months One patient survived 160+ monthsOne patient survived 160+ months
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AML: the ECOG experience
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AML: the ECOG experience
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AML: the ECOG experience
Study limitationsStudy limitations No children, so Downs cases not No children, so Downs cases not
includedincluded Fibrotic marrow makes diagnosis Fibrotic marrow makes diagnosis
difficultdifficult Poor prognosis may lead to less referral Poor prognosis may lead to less referral
for studiesfor studies
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Second SeriesSecond Series
Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center From Blood in 2006. 37 patient with AML M7 at MD Anderson
from 1987-2003 2% of all patients with new diagnosis of
AML Treated with one of five regimens
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CytogeneticsCytogenetics
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M.D. Anderson Cancer Center
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OutcomesOutcomes
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SummarySummary
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Patient PresentationPatient Presentation
Achieved CR after induction chemoAchieved CR after induction chemo
Outcome???Outcome???
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ConclusionsConclusions
AML M7 is a rare form of AML with AML M7 is a rare form of AML with a very poor prognosisa very poor prognosis
+/- prognostic indicators are not +/- prognostic indicators are not well understoodwell understood
Optimal treatment is not known at Optimal treatment is not known at this timethis time
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Questions?Questions?
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ResourcesResources Abeloff:Abeloff: Clinical Oncology, 3rd ed.,Clinical Oncology, 3rd ed.,
2004 Churchill Livingstone2004 Churchill Livingstone http://www.meds.com/leukemia/http://www.meds.com/leukemia/
points/lect1.htmlpoints/lect1.html Lowenberg, B. et al. Lowenberg, B. et al. Acute Myloid Acute Myloid
LeukemiaLeukemia, N Engl J Med , N Engl J Med 1999;341:1051-621999;341:1051-62
Martin, et al. Martin, et al. Acute Acute megakaryocytic leukemia: the megakaryocytic leukemia: the Eastern Cooperative Oncology Eastern Cooperative Oncology Group experience.Group experience. Blood 2000; Blood 2000; 96:2405-1196:2405-11
UpToDateUpToDate Yasuhiro, et al. Yasuhiro, et al. Adult acute
megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center. Blood 2006; 107:880-84Blood 2006; 107:880-84
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AML: the ECOG experience One surviving patient on trial: EST 3483:
1 – 2 courses of induction with daunorubicin 60 mg/m2 IV per day for 3 days, cytosine arabinoside 200 mg/m2 IV for 5 days plus 6-thioguanine 100 mg/m2 orally q12 hrs for 5 days.
Then randomized to either one course of intensive consolidation therapy with high-dose cytosine arabinoside 3 gm/m2 IV q12 hours days 1 to 6, plus amsacrine 100 mg/m2 per day IV on days 7 to 9 or maintenance therapy for 2 years with 6-thiogranine 40 mg/m2 twice daily each week plus cytosine arabinoside 60 mg/m2 subcutaneously on day 5 each week or observation.
Patients younger than 41 years with a histocompatible sibling were to undergo allogeneic transplantation.
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M.D. Anderson Cancer Center
Group 1 contained regimens with cytarabine (ara-C) and anthracyclines.
Group 2 contained regimens with ara-C and fludarabine but not containing anthracyclines.
Group 3 contained regimens with topotecan Group 4 contained regimens with ara-C and
not anthracyclines, fludarabine, or topotecan.
Group 5 was regimens without ara-C.