Arsenic trioxide‐ and idarubicin‐induced remissions in relapsed acute promyelocytic leukaemia: Clinicopathological and molecular features of a pilot study

Abstract

Arsenic trioxide (As 2 O 3 ) effectively induces remissions in relapsed acute promyelocytic leukaemia (APL), but the safety of its long-term administration is unknown. The anthracycline idarubicin is highly active alone or in combination chemotherapy for the treatment of APL. To minimize arsenic exposure and based on the high sensitivity of APL cells to anthracyclines, we conducted a prospective study to evaluate induction with As 2 O 3 followed by consolidation with idarubicin in the treatment of APL in relapse. Eight patients were treated with As 2 O 3 at a daily dose of 10 mg until remission, followed by three monthly courses of idarubicin, at 6 mg/m 2 /day for 5 days in the first course and 6 mg/ m 2 /day for 2 days in the subsequent two courses. All patients achieved morphological but not molecular remission after As 2 O 3 treatment. During As 2 O 3 therapy, an increase in white cell count peaking at a median of 17 days occurred in all the cases. Serial flow cytometric analysis of apoptosis, with mitochondrial APO2.7 antigen expression and the sub-G1 cell fraction on DNA histogram as markers, showed induction of apoptosis of APL cells in vivo. With both qualitative and real-time quantitative polymerase chain reaction, all patients were shown to attain molecular remission after subsequent idarubicin treatment. With a median follow up of 13 months, seven of eight patients have remained in complete clinical remission, with six patients in molecular remission as well. One patient who was in third remission became PCR-positive after being transiently negative. One patient died from an intracranial extramedullary relapse after achieving marrow molecular remission. We conclude that As 2 O 3 induction followed by idarubicin consolidation is an effective therapy for APL in relapse. This regimen avoids the possible long-term toxicities of As 2 O 3 and mutagenicity of combination chemotherapy, a strategy that might be suitable for this potentially curable leukaemia. Am. J. Hematol. 66:274-279, 2001.

Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – A Europe Against Cancer Program

“…However, there have been relatively few studies reporting the use of RQ-PCR in APL patients. 41,[159][160][161] Although the molecular diagnosis and monitoring of APL patients represents one of the most relevant examples of the impact of molecular genetics in clinical hematology, further investigations are still needed.…”

Determinants of cerebrospinal fluid arsenic concentration in patients with acute promyelocytic leukemia on oral arsenic trioxide therapy

“…Oral As 2 O 3 (10 mg/day) 6 and idarubicin (6 mg/m 2 per day ϫ 3) were administered until complete remission (CR), followed by idarubicin consolidation (6 mg/m 2 per day ϫ 4) 7 and maintenance (all-trans retinoic acid, 45 mg/m 2 per day; oral As 2 O 3 , 5-10 mg/day; 2 weeks every 2 months for 2 years). As 2 O 3 treatment was approved by the institutional review board at Queen Mary Hospital and performed in accordance with the Declaration of Helsinki.…”

Oral arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia

“…5 Cases 1, 2, 3, 5, and 7 received one day of intravenous As 2 O 3 as part of the initial pharmacokinetic study. 4 All patients achieved CR2 with oral As 2 O 3 , given for a median of 37 days (range, 22-59 days).…”