Treatment with all-trans retinoic acid in acute promyelocytic leukemia reduces early deaths in children

All-trans retinoic acid (ATRA) is a known inducer of differentiation in acu te promyelocytic leukemia. To improve the outcome of children with acute pr omyelocytic leukemia, ATRA has been applied since 1994 as an additional ind uction element in the AML-BFM 93 study. In a retrospective study, we compar ed 22 children treated with ATRA (median age: 9.3 years; range: 1.8-16.3) w ith 22 patients receiving conventional therapy (median age: 12.3 years; ran ge: 3.2-16.7). Twenty-one of the children achieved complete remission. Only one patient died early from bleeding complications after 3 days administra tion of ATRA. In the control group, seven early deaths occurred (Fisher exa ct test; p<0.04). Two children died from intracerebral hemorrhages. Two pat ients suffered from sepsis during aplasia after induction therapy, and one child did not respond to treatment. The 5-year overall survival (OS) and ev ent-free survival (EFS) of the children who received ATRA followed by chemo therapy were significantly bettercompared with conventionally treated child ren [OS: 0.87+/-0.9 vs 0.45+/-0.11, p (log rank) <0.003; EFS: 0.76+/-0.11 v s 0.43+/-0.11 p (log rank) <0.02]; the median observation time was 2.8 year s (19-76 months). However, nearly all children suffered from common side ef fects such as headache, fever, joint, muscle and bone pain, weight gain, or dermatitis. In three patients, a retinoic acid syndrome was observed. Inte rruption of ATRA treatment and application of dexamethasone, necessary in 1 2 children, controlled theadverse effects. ATRA treatment could be resumed in 18 patients. In conclusion, ATRA treatment during induction could avoid early deaths in children with acute promyelocytic leukemia with considerabl e but manageable toxic side effects.