Acute Myeloid Acute Myeloid LeukemiaLeukemia

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

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

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

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

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???

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.

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

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

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

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

Bone Marrow BiopsyBone Marrow Biopsy

Diagnosis Diagnosis confirmed by confirmed by immunophenotypeimmunophenotype

http://www.lmp.ualberta.ca/resources/pathoimages/Images-A/000p0360.jpg

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

Leukemic Cellular OriginLeukemic Cellular Origin

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

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

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

PrognosisPrognosis

Prognosis after CRPrognosis after CR

PrognosisPrognosis

Overall for AML:Overall for AML: 70-80% CR70-80% CR 20-30% DFS at 5 years20-30% DFS at 5 years

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

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

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

DiagnosisDiagnosis

Anti glycoprotein IIb/IIIa (CD41a)

Platelet peroxidase by electron microscope

Immuno-cytochemistry stain for factor VIII

From http://www.ehatol.org

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)

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

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

AML: the ECOG experience

AML: the ECOG experience

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

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

CytogeneticsCytogenetics

M.D. Anderson Cancer Center

OutcomesOutcomes

SummarySummary

Patient PresentationPatient Presentation

Achieved CR after induction chemoAchieved CR after induction chemo

Outcome???Outcome???

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

Questions?Questions?

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

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.

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.