Extramedullary relapse after all-trans retinoic acid treatment in acute promyelocytic leukemia : the occurrence of retinoic acid syndrome is a risk factor

• Published in: Leukemia Vol. 13; no. 9; pp. 1406 - 1408
• Main Authors: KO, B.-S, TANG, J.-L, CHEN, Y.-C, YAO, M, WANG, C.-H, SHEN, M.-C, TIEN, H.-F
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.09.1999; Nature Publishing Group
• Subjects: Acids; Acute promyeloid leukemia; Adolescent; Adult; Aged; Biological and medical sciences; Chemotherapy; Confidence intervals; Drug toxicity and drugs side effects treatment; Female; Hematopoiesis, Extramedullary - drug effects; Humans; Leukemia; Leukemia, Promyelocytic, Acute - drug therapy; Male; Medical sciences; Patients; Pharmacology. Drug treatments; Promyeloid leukemia; Recurrence; Remission; Remission Induction - methods; Retinoic acid; Retrospective Studies; Risk analysis; Risk Factors; Syndrome; Toxicity: blood; Tretinoin - therapeutic use; Antineoplastic agent; Human; Promyelocytic leukemia; Relapse; Toxicity; Acute; Retinoid; Malignant hemopathy; Chemotherapy; Treatment; Dissemination; Risk factor; Complication; Extramedullary; Tretinoin
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2401495

All-trans retinoic acid (ATRA) is now a standard agent for remission induction of acute promyelocytic leukemia (APL). Recently, extramedullary relapse, which was a rare condition in APL patients after chemotherapy alone, was reported with an increased frequency after ATRA treatment. However, it is not yet clear whether ATRA truly increases the risk of extramedullary recurrence and what are the risk factors. In this study, three of 13 patients with recurrent APL after prior treatment of ATRA were found to have extramedullary involvement, compared with none in 11 recurrent patients previously treated with chemotherapy alone (estimated relative risk 2.100, 95% confidence interval 1.341-3.289). Furthermore, in the former group of patients, the development of retinoic acid (RA) syndrome during prior induction treatment was significantly associated with extramedullary involvement at relapse (three in five patients with RA syndrome vs none in eight without the syndrome, estimated relative risk 5.000, 95% confidence interval 1.448-17.271). In conclusion, ATRA may predispose APL patients to extramedullary involvement at relapse and the occurrence of RA syndrome is a risk factor for it. Further studies are needed to confirm these findings. It also remains to be clarified whether treatment modification is necessary in patients who develop RA syndrome during ATRA treatment.