What is the efficacy of induction therapy in the treatment of acute promyelocytic leukemia (APL)?

Updated: May 03, 2019
  • Author: Sandy D Kotiah, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

In the PETHEMA study (LPA 96 and 99), 426 patients with newly diagnosed APL were given induction therapy with ATRA and idarubicin (AIDA regimen). The study was started in 1996 and was called LPA 96. However, the study was modified after 1999 (LPA 99) to give intermediate- and high-risk patients consolidation with ATRA and higher doses of anthracyclines. The complete remission rate was 90%. All of the patients received 2 years of maintenance therapy. The 3-year risk of relapse was lower in the LPA 99 arm (8.7% vs 20.1%).

In the French-Belgian-Swiss study (APL 2000)< study, 413 patients younger than age 75 years with newly diagnosed APL were randomized to ATRA followed by chemotherapy versus ATRA with concurrent chemotherapy. The first arm had to achieve remission with ATRA before chemotherapy, with 7 days of cytarabine at 200 mg/m2 and 3 days of daunorubicin at 60 mg/m2. The second arm had chemotherapy added on day 3. These patients were then randomized to four different maintenance arms: observation, ATRA, chemotherapy, or ATRA with chemotherapy.

The complete remission rate was 92%. The results revealed that the early addition of chemotherapy lead to significantly better survival, and the lowest relapse risk was seen in patients with ATRA and chemotherapy maintenance.

Ades et al compared results of the French-Belgian-Swiss group and the PETHEMA group for patients younger than 65 years and concluded that in both groups, patients with WBC < 10,000/μL had similar 3-year survival rates. [27] However, for patients with WBC >10,000/μL, the complete remission rates and 3-year free survival rates were higher in the APL 2000 trial, and risk of relapse was lower. These findings were statistically significant and suggested a beneficial role for cytarabine for induction chemotherapy in high-risk patients.

De la Serna et al reported on the incidence, time of occurrence, and prognostic factors of induction failure in a population of 732 patients with APL. [28] The most common causes of induction failure included hemorrhage, infection, and APL differentiation syndrome (a rapid rise in WBC count during APL treatment, resulting in hyperleukocytosis). A multivariate analysis showed that certain pretreatment factors correlated with these adverse events. For example, elevated creatinine levels, presence of high peripheral blood blasts, and coagulopathy increased the risk of death.

Infection was seen more frequently in men older than 60 years and patients who had fever at presentation. [28] APL differentiation syndrome was linked to a lower serum albumin level and an Eastern Cooperative Oncology Group (ECOG) score >1.

In low- and intermediate-risk patients, the NCCN recommends continuing induction therapy until count recovery occurs, then proceeding to consolidation therapy. In high-risk patients receiving ATRA/ATO, induction is continued until count recovery and bone marrow remission are demonstrated. In high-risk patients receiving other regimens, count recovery and lumbar puncture results are indications for proceeding to consolidation therapy. [14]


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