Retinoic acid and APL
Acute Promyelocytic Leukemia (APL)

TREATMENT

• APL is unique among the leukemias distinguished by its sensitivity to all-trans retinoic acid (ATRA), a derivative of vitamin A.

• ATRA is a form of "differentiation therapy."

• It activates the retinoid receptor RAR and causes differentiation of the immature leukemic promyelocytes into mature granulocytes.

• ATRA is typically combined with anthracycline based chemotherapy resulting in a clinical remission in approximately 90% of patients. However, ATRA cannot eliminate the leukemic clone.

• ATRA therapy is associated with the unique side effect of retinoic acid syndrome. This is associated with the development of dyspnea, fever, hypotension, weight gain, peripheral edema and is treated with dexamethasone.
  The etiology of retinoic acid syndrome has been attributed to capillary leak syndrome from cytokine release from the differentiating promyelocytes.

• Treatment options for patients with relapsed disease include arsenic trioxide and allogenic stem cell transplant.

PROGNOSIS

• Better with the combination of ATRA and chemotherapy than chemotherapy alone in newly diagnosed APL, because ATRA + chemotherapy makes for a slightly higher rate of complete remissions while allowing significantly fewer relapses. Maintenance treatment with ATRA, and possibly with low-dose chemotherapy, further reduces the incidence of relapse.

• Depends on a number of factors including the white blood cell (WBC) count at the time of diagnosis, etc.
  Overall,

• more than 90% of patients with newly diagnosed APL today can achieve complete remission

• about 75% can be cured by the combination of ATRA and chemotherapy.