APL - Acute Promyelocytic Leukaemia

• APL is a subtype of acute myeloid leukemia (AML)
• APL makes up 10% of AML among adults
• Treatment with cytostatics gives remission in 60-80% of the patients. Serious side-effects
• Five-year survival is 35-45%
• In 1980 Breitman et al. showed that retinoic acid induces granulocyte differentiation and inhibits growth (proliferation) of APL cells in culture.
• Eight years later Huang et al. showed that 95% of patients with APL went into remission with retinoic acid treatment (also patients that were resistant to cytostatics). Mild side effects.

Hematopoiesis

Hematopoiesis starts with a pluripotent stem cell in the bone marrow that can differentiate into a myeloid or lymphoid stem cell. Overview of hematopoiesis

Development of APL

From the myeloid stem cell a platelet stem cell, an erythrocyte stem cell or a myelo-monocyte stem cell can develop. The myelo-monocyte stem cell can further develop in two ways, either becoming a monoblast (for development into a moncyte), or becoming a myeloblast (for development into a granulocyte monoblast). If the maturation of promyelocytes into granulocytes is blocked - the result is APL.

Treatment of APL

• Combination of RA and conventional anthracyclin-ARA-C cytostatics now gives >90% complete remission in all multicenter studies
• Further therapy with RA and chemotherapy (1-2 years) reduces the risk of relapse to 10-15%
• The RA syndrome is the most important side-effect, found in 10-15% of the patients: fever, respiration problems, hypertension, kidney failure => may cause death
• The RA syndrome can be treated with cytostatics and steroids, but is fatal in 10% of the patients
• Now, retinoic acid is given for short periods to avoid the RA syndrome.

Ref: Fenaux, Chomienne, Degos: Treatment of APL. Best. Pract. Res. Clin. Haematol (2001)