Acute Myeloid Leukemia (AML)

Definition

• neoplastic proliferation of myeloid blast cells

Epidemiology

• rapid progression 
  - death ~2/12 if untreated
  - ~20% 3-yr survival after Rx
• commonest acute leukemia of adults
  - incidence increases w age

Risk Factors

• can be LT complication of chemotherapy
• also associated w myelodysplastic states, radiation, syndromes (eg. Down's)

History

• marrow failure: anemia, infection, bleeding
  - DIC occurs in acute promyelocytic leukemia
• infiltration: hepato- & splenomegaly, gum hypertrophy, skin involvement

Acute promyelocytic leukemia (APL) differs from AML in that most patients present with coagulopathy. The coagulopathy has been described as DIC with associated hyperfibrinolysis. Acute promyelocytic leukemia (APL) has been associated with low levels of plasminogen, alpha2-plasmin inhibitor, and plasminogen activator inhibitor 1 found in fibrinolytic states. There is increased expression of annexin II, a receptor for plasminogen and plasminogen-activating factor, on the surface of leukemic promyelocytes.[7] This leads to overproduction of plasmin and fibrinolysis.

emedicine.medscape (http://emedicine.medscape.com/article/1495306-clinical)

Investigation results
*Dx now based on immunophenotyping & molecular methods - cytogenetic analysis affects Rx recommendations & guides prognosis

• WCC often elevated but can be low or normal
• blast cells may be few in peripheral blood (-> Dx on bone marrow biopsy)
• auer rods

Treatment

• supportive care
  - walking can relieve fatigue
  - bloods, platelets, IV fluids given as necessary
  - G-CSF between chemo cycles
  - neutropenic regimen
• chemotherapy
  - daunorubicin, cytarabine
  - ~5 cycles given in 1 week blocks to achieve remission
• bone marrow transplant
  1. allogeneic
  ^from HLA-matched siblings / unrelated donor
  ^indicated during 1st remission in disease w poor prognosis
  ^use cyclophosphamide+total body irradiation to destroy leukemic cells & immune system before transplant
  ^ciclosporin+methotrexate may be used to reduce graft vs host disease 
  ^^complications: GVDH, opportunistic infections, relapse of leukemia, infertility
  ^^prognosis: lower relapse rates, ~60% LT survivors, ~10% mortality
  
  2. autologus
  ^used in intermediate prognosis disease
  ^autologus mobilised peripheral blood stem cell transplant may offer faster hematopoietic recovery & less morbidity