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Evolving primary cancer treatments spur changes in secondary APL rates
Changes to the treatment of primary tumors are associated with increased rates of secondary acute promyelocytic leukemia among patients with prostate cancer but decreased rates among patients with breast cancer, according to study results.
Characteristics and outcomes were similar among patients with secondary or de novo acute promyelocytic leukemia (APL), results also showed.
“APL generally occurs de novo, without a known cause,” Pierre Fenaux, MD, PhD, of the department of hematology seniors at the Hôpital Saint-Louis in Paris, and colleagues wrote. “However, secondary APL that emerges after chemotherapy and/or radiotherapy for neoplastic or non-neoplastic disorders has been increasingly described, including in our group’s experience, and represented from 10% to 20% of all patients with APL in a recent series.”
Fenaux and colleagues from the French-Belgian-Swiss APL Group evaluated data from patients with secondary (n = 42) or de novo (n = 238) APL who were enrolled in their APL-2006 trial.
The analysis also included a comparison of the 42 patients with secondary APL with a retrospective historical cohort of 106 patients who were diagnosed with therapy-related APL between 1982 and 2001.
APL was considered secondary if it occurred after primary disease, regardless of treatment, or after a non-neoplastic disease treated by chemotherapy, radiation or drug therapy.
The primary disease was neoplastic in all 42 patients with secondary APL, and included breast cancer, prostate cancer, other solid tumors and lymphoma. A smaller proportion of these patients had primary breast carcinoma (35.7% vs. 57%; P = .03), and a greater proportion had primary prostate carcinomas (26.2% vs. 4.7%; P ˂ .001) compared with the historical cohort.
Patients in the current cohort received less combined chemotherapy and radiation than the historical cohort (29.6% vs. 47.2%; P = .044) and were more likely to receive radiation alone (40.5% vs. 25.4%) for the treatment of the primary tumor.
Among patients with primary breast cancer, no patients in the current cohort received mitoxantrone compared with 46.7% of the historical cohort (P = .016); however, a greater proportion received anthracyclines (53.3% vs. 38.3%; P = .015). Among those with primary prostate cancer, more patients in the historical cohort received anti-estrogens (0% vs. 80%; P = .002).
Median interval between primary disease diagnoses and secondary APL was 48 months (range, 6-299 months) in the current cohort and 25 months (range, 4-276) in the historical cohort.
Among patients in the prospective cohort, patients with secondary APL were older than patients with de novo APL (mean age, 60.2 years vs. 48.7 years; P < .0001) and were more likely to display a breakpoint cluster region 3 breakpoint (35% vs. 57.2%; P = .0093). Sex, baseline white blood cell count and the proportion having the hypogranular variant of APL were comparable between the cohorts.
Researchers noted the complete response rate was similar in patients with secondary vs. de novo APL (97.6% vs. 90.3%). Relapse (0% vs. 1.8%) and OS (92.9% vs. 90.9%) rates also were similar.
“Our findings suggest that the efforts made to reduce the risk of secondary APL, especially by avoiding the use of mitoxantrone in breast carcinoma, have changed the types of primary tumors and their treatment in recently diagnosed patients with secondary APL, but they may not have reduced the incidence of secondary APL,” Fenaux and colleagues concluded. “Our study also confirms prospectively that patients with secondary APL have characteristic and outcomes similar to those of patients with de novo APL; however, a longer median follow-up will be necessary to confirm that secondary APLs are not associated with more frequent relapses.”– by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures.