Treatment of Relapsed Acute Promyelocytic Leukemia with Oral Arsenic Trioxide: An Eleven-Year Experience

• Published in: Blood 2008-11, Vol.112 (11), p.2958-2958
• Main Authors: Au, Wing-Yan, Tam, Sidney, Leung, Anskar Y.H., Tse, Eric, Kumana, Cyrus, Kwong, Yok Lam
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V112.11.2958.2958

Background. For patients with relapsed acute promyelocytic leukemia (APL), the optimal therapy after arsenic trioxide (As2O3)-induced complete remission (CR) is unclear. Autologous or allogeneic hematopoietic stem cell transplantation (HSCT) has been advocated. These strategies are associated with morbidity and considerable mortality, and not all patients are eligible. The role of maintenance therapy with As2O3 remains undefined. Materials and methods. From 1997–2008, 50 consecutive APL patients (25 men, 25 women, median age: 35 (12–72) years) in relapse (R1, n=47; R2, n=3) were treated with As2O3 until CR. This was followed by idarubicin consolidation (6 mg/m2/day × 9) in 43 patients. Seventeen patients did not receive maintenance treatment. Thirty-two patients received oral-As2O3 maintenance (10 mg/day × 14 every 2 months). All-trans retinoic acid (ATRA, 45 mg/m2/day) maintenance was used together with oral-As2O3 in 27 patients. As2O3 protocol was approved by the institutional review board at Queen Mary Hospital. All maintenance treatment was given in the outpatient clinic as oral medication. Results. Of 50 relapsed cases, As2O3-induced CR was achieved in 49 patients, 1 patient dying of pneumonia. At a median follow-up of 61 (6–122) months, 27 patients (19 with and 8 without As2O3 maintenance) had remained in remission. Further relapses (R2, n=20; R3, n=2.) occurred in 22 patients (13 with and 9 without As2O3 maintenance), at a median of 16 (6–28) months. Concomitant central nervous system (CNS) relapse occurred in 8 cases. Treatment of post-As2O3 relapses included oral-As2O3 (10 mg/day) + ATRA (45 mg/m2/day) with (n=10) or without (n=10) ascorbic acid (1 gm/day) until CR, and then maintenance with As2O3 + ATRA +/− ascorbic acid. Leucocytosis during treatment was controlled with mitoxantrone. In these 22 cases of post-As2O3 relapses, further remission was still achieved in 19 patients (CR3, n=18; CR4, n=1), with 3 patients dying from cerebral bleeding. At a median follow-up of 88 (8–98) months, 8 patients had remained in remission. Further relapses occurred in 11 patients. Salvage therapy consisted of As2O3+ATRA+ascorbic acid, together with chemotherapy (mitoxantrone, n=8; amascrine, n=3), gemtuzumab ozogamicin (n=4), and autologous HSCT (n=1). Eight patients finally died of refractory leukemia after a median of 6 (2–33) months. Three patients had remained in remission (CR4, n=2, CR5 n=1) at a median of 41 (26–102) months. On an intention-totreat basis,