Long-term outcome of relapsed acute promyelocytic leukemia treated with oral arsenic trioxide-based reinduction and maintenance regimens: A 15-year prospective study

Cancer. 2018 Jun 1;124(11):2316-2326. doi: 10.1002/cncr.31327. Epub 2018 Mar 26.

Abstract

Background: For patients who have acute promyelocytic leukemia (APL) in second complete remission (CR2), optimal postremission strategies remain undefined.

Methods: The role of an oral arsenic trioxide (As2 O3 )-based regimen in the management of patients who had APL in CR2 was examined.

Results: Seventy-three patients with APL in first relapse (R1) were studied. Oral As2 O3 -based reinduction resulted uniformly in CR2, irrespective of previous As2 O3 exposure. All patients received oral As2 O3 -based maintenance in CR2. At a median follow-up of 94 months (range, 9-205 months), 43 patients (58.9%) were still in CR2, and 49 (67.1%) had finished the planned 2-year CR2 maintenance with all-trans retinoic acid, oral As2 O3 , and ascorbic acid. Reinduction and maintenance treatments were well tolerated. Grade 1 and 2 headache occurred in 20 patients (27.4%). Hepatotoxicity, all in the form of transaminitis, occurred in 35 patients (47.9%; grade 1 and 2, n = 26; grade 3 and 4, n = 9). Three patients had self-limiting QTc prolongation. The 10-year leukemia-free survival rate was 56.8%. Thirty patients developed R2. Oral As2 O3 -based reinduction led to CR3 in 27 patients (90%). Post-CR3 strategies included autologous hematopoietic stem cell transplantation and oral As2 O3 maintenance. At a post-CR3 follow-up of 30 months (range, 3-166 months), 11 patients were still in CR3. The 5-year and 10-year overall survival rates in the R1 cohort were 79.5% and 67.3%, respectively. Prior receipt of oral As2 O3 maintenance in CR1 was the only risk factor for inferior leukemia-free survival. Central nervous system involvement occurred in 15 patients, including 5 who remained alive. Relapse during oral As2 O3 therapy was the only significant risk factor for central nervous system involvement.

Conclusions: For patients with relapsed APL, As2 O3 remained effective despite repeated As2 O3 exposures. Oral As2 O3 maintenance was an effective postremission strategy for CR2. Cancer 2018;124:2316-26. © 2018 American Cancer Society.

Keywords: acute promyelocytic leukemia; oral arsenic trioxide maintenance; relapse; second complete remission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Arsenic Trioxide / administration & dosage*
  • Arsenic Trioxide / adverse effects
  • Ascorbic Acid / administration & dosage
  • Ascorbic Acid / adverse effects
  • Chemical and Drug Induced Liver Injury / diagnosis
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / etiology
  • Combined Modality Therapy / methods
  • Disease-Free Survival
  • Female
  • Headache / chemically induced
  • Headache / diagnosis
  • Headache / epidemiology
  • Hematopoietic Stem Cell Transplantation
  • Hong Kong / epidemiology
  • Humans
  • Leukemia, Promyelocytic, Acute / mortality
  • Leukemia, Promyelocytic, Acute / therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / therapy*
  • Prospective Studies
  • Remission Induction / methods*
  • Risk Factors
  • Severity of Illness Index
  • Survival Analysis
  • Time Factors
  • Transplantation, Autologous
  • Tretinoin / administration & dosage
  • Tretinoin / adverse effects
  • Young Adult

Substances

  • Tretinoin
  • Ascorbic Acid
  • Arsenic Trioxide