A randomized study with or without intensified maintenance chemotherapy in patients with acute promyelocytic leukemia who have become negative for PML-RARα transcript after consolidation therapy: The Japan Adult Leukemia Study Group (JALSG) APL97 study

Abstract

To examine the efficacy of intensified maintenance chemotherapy, we conducted a prospective multicenter trial in adult patients with newly diagnosed acute promyelocytic leukemia treated with alltrans retinoic acid and chemotherapy. Of the 302 registered, 283 patients were assessable and 267 (94%) achieved complete remission. Predicted 6-year overall survival in all assessable patients and disease-free survival in patients who achieved complete remission were 83.9% and 68.5%, respectively. A total of 175 patients negative for PML-RAR␣ at the end of consolidation were randomly assigned to receive either intensified maintenance chemotherapy (n ‫؍‬ 89) or observation (n ‫؍‬ 86). Predicted 6-year disease-free survival was 79.8% for the observation group and 63.1% for the chemotherapy group, showing no statistically significant difference between the 2 groups (P ‫؍‬ .20). Predicted 6-year survival of patients assigned to the observation was 98.8%, which was significantly higher than 86.2% in those allocated to the intensified maintenance (P ‫؍‬ .014). These results indicate that the intensified maintenance chemotherapy did not improve disease-free survival, but rather conferred a significantly poorer chance of survival in acute promyelocytic leukemia patients who have become negative for the PML-RAR␣ fusion transcript after 3 courses of intensive consolidation therapy. (Blood. 2007;110:59-66)

How to manage acute promyelocytic leukemia

“…One explanation to this situation could be that the JALSG trial only compared no maintenance versus six courses of intensified maintenance chemotherapy rather than ATRA maintenance. 77 Although ATRA plus chemotherapy was originally considered to be the best solution of maintenance therapy, with our in-depth in vitro study on the mechanisms of ATRA and ATO, a better understanding has been obtained on the importance of the combined use of various drugs with different therapeutic targets. Thus, for the maintenance treatment, we have been optimizing the idea of ATO/ATRA combined with chemotherapy.…”

A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia

“…5 Despite this, these regimens have markedly increased the rate of complete remission and the long-term outcome of APL patients, approximately 10-30% of patients will suffer from recurrent disease within a period of 5 years. 5,34,35 This clinical outcome implicates that ATRA/anthracycline therapy will not target dysregulated genes and pathways sufficiently in all APL patients.…”

Chronic Myeloid Leukemia Developing After Successful Treatment of Acute Promyelocytic Leukemia

“…Based on Japanese study, patients with APL who received VP-16 for consolidation therapy had a high incidence (10.2 %) of therapy-related myeloid neoplasms(t-MN) [10]. Furthermore, the accumulation of chemotherapeutic agents in maintenance phase may also increase the risk of t-MN [11]. Data from Programa Español para el Tratamiento de Enfermedades Hematológicas study showed that t-MN developed in 1.8 % APL patients who received ATRA and anthracycline-based chemotherapy [12].…”