• age
• cytogenic abnormalities

We also use molecular genetic alterations to predict outcome

• 15-20% of acute leukemias in kids and 80% in adults
• slightly more in males
• predominant form in neonatal peroid
• incidence increasing esp. in older population (age>60)

• Down's syndrome
  • 10-18 fold increase for AML
  • high incidence of transient myeloproliferative disease (TMPD)
• Kostmann's syndrome (infantile agranulocytosis)- mut. in G-CSF receptor on chromosome 1p
• Diamond Blackfan anemia (congenital hypoplastic anemia and growth retardation)
• Blooms
• Fanconi anemia
• Wilkott Aldrich
• Klinefelters
• Patau's

• alkylating agents
  • must have long exposure over time and high dose
  • ex: Melphalan, nitrosureas
  • MDS phase with evolution of AML 5-10 yrs after exposure
  • chromosomal abnormalities on 5, 7, and some 8

• no MDS phase and short latency phase
• monocytic morphology
• balanced translocation involving band 11q and varying partner (6, 9, or 19)

• antineoplastic agents
  • alkylating agents
  • topoisomerase II inh.
• radiation
• atecendent hematologic disorder
• chemical exposure
  • organic solvents (benzene, carbon tetrachloride, kerosene)
  • smoking- modest increase in risk and double increase in pts over 60
• retrovirus (no clear association)

• cytogenetics (Fab was more morphological)
• molecular genetics
• therapy related leukemias
• biphenotypic leukemias

Lower threshold of blasts which establish dx from 30% to 20%

• hyperleukocytosis
  • in microgranular APL and AML with monocytic differentiation
  • more than 100,000 myeloblasts/microL
• coagulation abnormalities (ex: DIC)
  • abnormal platelet function
  • consumptive coagulopathy (ex: DIC) especially in APL (M3)
• metabolic abnormalities
  • tumor lysis syndrome
• hepatosplenomegally
• extramedullary presentations/granulocytic sarcoma (usually with 8:21 translocation) 
  • can be apparent before detectable leukemia
  • rare
  • mainly FAB M5
  • high peripheral blast count
  • CD 56 expression (neural crest adhesion molecule)

• increase soft tissue involvement (skin, gingiva, LN, lungs)
• CNS involvement

• common intense marrow fibrosis
• mediastinal germ cell tumors

• anemia universally present
• thrombocytopenia is nearly always present (decreased production and survival)
• leukopenia in half of patients with absolute neutropenia
• myeloblasts are almost always present in the blood (difficult to ID in leukopenic patients)
• Auer rods (elliptical cytoplasmic inclusions) present in myelblasts in 30% of pts

• old age
• high WBC at dx
• MDR1 gene present
• prevois hematological myelodysplasia
• chromosomal abnormalities with 11 translocation with 5 or 7

• 8:21 translocation
• 15:17 transolcation
• inversion 16 

• 8, 21 translocation
• inversion 16
• 16, 16 translocation

• favorable prognosis in adults and poor outcome in kids
• adults, median age is 25-30
• most commmon in childhood AML
• 18% of all acute leukemias and 40% of M2 with abnormal karyotypes

1. AML1 gene on chrom 21 fuse with ETO gene on 8
2. cause altered transcriptional regulation of normal AML1 target genes and activation of new target genes that prevent apoptosis

• most common cytogenic abnormality associated with EMD
• EMD has poor prognosis

• ecessive or morphological abnormal bone marrow eosinophils
• favorable prognosis
• pathogenesis- CBFB/MYH11 fusion protein
• common in FAB M4 subtype

• induction tx treduce leukemic cell population by 10^3 (to achieve remission)
• substantial burden of leukemic cell persists undetected (minimal residual disease) that leads to relpase if no additional tx given
• post remission or consolidation tx is needed

Induction with more tx after achieve remision

• Ara C
• Daunorubicin or Idarubicine

Associated with remission in 60-80% of those taking it

• less than 5% marrow blasts
• marrow with 20% cellularity
• absense of EM leukemia
• hematological recovery

Achieve CR = improved survival

above are predictors out outcome

• autologous stem cell therapy
  • same efficacy as standar therapy
  • no effect on OS no benefit on DFS
• several courses of high dose Ara-C
• allogenic SCT
  • good risk AML- no survival benefit, so we dont do it in this group
  • done on those wwith intermediate/ poor risk
    • reduced relapse rate and improved DFS
    • benefit in younger pts due to decreased transplant related deaths

• median age 40 yrs
• increase incidence in Lations
• non increase incidence with ages
• no prior MDS
• can occur after therapy with Etoposide, doxorubicine, bimolane

• lower WBC at dx
• DIC and primary fibrinolysis (can have fatal bleed)