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Acute Myeloid Leukemia

Acute Myeloid Leukemia. Case Presentation. 33 yo Filipino male presents with back pain, fevers, weight loss, and general malaise Not felt “normal” in two months Previously healthy Sent to NMCSD by PCM for abnormal labs. PE. Mostly unremarkable exam BP: 187/110; HR: 123; T – 98.7; R - 16

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Acute Myeloid Leukemia

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  1. Acute Myeloid Leukemia

  2. Case Presentation • 33 yo Filipino male presents with back pain, fevers, weight loss, and general malaise • Not felt “normal” in two months • Previously healthy • Sent to NMCSD by PCM for abnormal labs

  3. PE • Mostly unremarkable exam • BP: 187/110; HR: 123; T – 98.7; R - 16 • Normal CV/Pulm exam • No lymphadenapathy • Mild hepatomegaly, no spleenomegaly • No ecchymoses or rash • Mild resting tremor

  4. Labs • CBC: • H/H: 14.1/43 • WBC: 11.4 • Diff: N – 69/Bands - 7/L - 18/M - 10/E - 2 • Platelets: 54 • Calcium – 11.0; Phos – 6.9 • LDH - 3752

  5. AML – The Basics • AML accounts for 40% of leukemia cases. • Approximately 10,000 cases are diagnosed in adults in the US annually. • The incidence of AML increases steadily with increasing age. The median age is 55 to 60. • Males > females; whites > blacks. Abeloff: Clinical Oncology, 3rd ed

  6. AML – The Basics • Increased incidence with Down's syndrome, Bloom's syndrome, Fanconi's anemia • Increased risk with MDS and MPS. • Multiple environmental risk factors: • exposure to radiation • chemical exposure to benzene, hydrocarbons, and solvents • treatment with alkylating agents • Viruses???

  7. Presentation • Lethargy, granulocytopenia, and thrombocytopenia are most common. • 30% present with a significant skin, soft tissue, or respiratory infection. • Petechiae with or without bleeding may be present. • Hyperuricemia is frequent; splenomegaly is present in about 1/3 of patients. • Lymphadenopathy and hepatomegaly are uncommon.

  8. Work-up • History • family, work, and medical history • radiation and chemical exposure history • Physical • Temperature • Cranial nerve exam and vision exam • Lymph nodes and hepatosplenic exam • Special attention to potential sites of infection

  9. Peripheral Smear • Nonspecific findings: • Normochromic, normocytic anemia • Thrombocytopenia • Leukopenia (with granulocytopenia) • May have leukemic blasts

  10. Diagnosis • Bone Marrow Biopsy • Cellularity • Stains: • Wright's, Sudan black, esterase stains • Periodic acid-Schiff reagent, iron stain, and immunofluorescent stain • Aspirate for karyotyping and immunophenotyping

  11. Bone Marrow Biopsy • Must have >30% blasts (WHO >20% blasts) • Must be myeloid origin • Auer rods found in most AML http://www.microscopy-uk.org.uk/mag/artaug01/vrcoolpixb.html

  12. Bone Marrow Biopsy • Diagnosis confirmed by immunophenotype

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

  14. AML -Pathology • Abnormal clonal proliferation of a primitive myloid hematopoietic progenitor cell • Accumulation in bone marrow results in pancytopenia • Leukemic cells released into circulation

  15. Leukemic Cellular Origin

  16. AML - Types • Classified in the FAB system • Classified using: • Morphologic appearance of the blasts • Myeloperoxidase stain • Sudan black stain • Nonspecific esterases • Cytogenetic testing • Immunologic testing

  17. Treatment • Induction • 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 • Post Induction Therapy • Allogenic bone marrow transplant • Autologous bone marrow transplant • Chemotherapy

  18. Treatment • Remission: • Achieved after 7/3 in 70-80% of patients under the age of 60 • Achieved in 50% of patients older than 60 • Relapse • Occurs on average 4 months after induction if no further treatment

  19. Prognosis

  20. Prognosis after CR

  21. Prognosis • Overall for AML: • 70-80% CR • 20-30% DFS at 5 years

  22. Special Cases • AML M3 (Acute promyelocytic leukemia) • Induction with all-trans retinoic acid, followed by daunorubicin and cytarabine • High risk of DIC

  23. Patient Presentation • Bone Marrow biospy • 1st sample was fibrotic • 2nd sample – AML M7 • Leukemic cells CD61 + • Negative for other stains • Trilineage hypoplasia • Extensive bone marrow necrosis Stain for CD61 (Glycoprotein IIIa) http://www.ihcworld.com

  24. AML M7 • Acute Megakaryoblastic Leukemia (FAB M7) • Accounts for 3-5% of AML (not associated with prior treatment) • Overall poor prognosis • Down Syndrome increases risk • Commonly presents with a dry bone marrow aspirate • Few large studies

  25. Diagnosis Anti glycoprotein IIb/IIIa (CD41a) Immuno-cytochemistry stain for factor VIII Platelet peroxidase by electron microscope From http://www.ehatol.org

  26. AML 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)

  27. Study Treatments • Patients enrolled in 5 different studies • Different doses daunorubicin and cytarabine • Other agents added: 6-thiogranine, idarubicin, GM-CSF • Consolidation with chemo or transplant

  28. AML: the ECOG experience • Outcomes: • 50% CR rates • Medial remission: 10.6 months • Median survival: 10.3 months • One patient survived 160+ months

  29. AML: the ECOG experience

  30. AML: the ECOG experience

  31. AML: the ECOG experience • Study limitations • No children, so Downs cases not included • Fibrotic marrow makes diagnosis difficult • Poor prognosis may lead to less referral for studies

  32. Second 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

  33. Cytogenetics

  34. M.D. Anderson Cancer Center

  35. Outcomes

  36. Summary

  37. Patient Presentation • Achieved CR after induction chemo • Outcome???

  38. Conclusions • AML M7 is a rare form of AML with a very poor prognosis • +/- prognostic indicators are not well understood • Optimal treatment is not known at this time

  39. Questions?

  40. Resources • Abeloff:Clinical Oncology, 3rd ed.,2004 Churchill Livingstone • http://www.meds.com/leukemia/points/lect1.html • Lowenberg, B. et al. Acute Myloid Leukemia, N Engl J Med 1999;341:1051-62 • Martin, et al. Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience. Blood 2000; 96:2405-11 • UpToDate • Yasuhiro, et al. Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center.Blood 2006; 107:880-84

  41. 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.

  42. 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.

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