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Arsenic trioxide, stem cell harvest sequence shows promise in APL
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Sequential treatment involving consolidation therapy with arsenic trioxide was associated with encouraging survival outcomes in a cohort of patients with acute promyelocytic leukemia.
Researchers conducted the phase 2 study to evaluate the efficacy and feasibility of a sequential treatment regimen for relapsed acute promyelocytic leukemia (APL).
The regimen included induction and consolidation with arsenic trioxide, peripheral blood stem cell harvest after high-dose cytarabine chemotherapy and autologous hematopoietic cell transplantation.
The analysis included 35 patients accrued between 2005 and 2009. Nine of those patients had molecular relapse, and 26 had hematologic relapse.
Complete remission was reported in 81% of patients who underwent induction therapy. All but four patients became negative for PML/RARalpha after the first arsenic trioxide consolidation course.
The second arsenic trioxide consolidation course yielded further reductions in transcript levels in three patients.
Twenty-five patients underwent peripheral blood stem cell harvest. All of these patients reached the target for CD34+ cell doses.
Autologous hematopoietic stem cell transplantation with PML/RARalpha-negative peripheral blood stem cell graft was performed in 23 of these patients. Three patients experienced a relapse after transplant. However, no transplant-related mortality was reported.
The median follow-up duration was 4.9 years. At that point, the rate of 5-year EFS was 65% and the OS rate was 77%.
Perspective
Back to TopCharles A. Schiffer, MD
Physicians who treat acute progranulocytic leukemia (APL) are blessed by the availability of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which — when used in combination — can cure more than 80% of newly diagnosed patients. As shown in this report from Japan by Yanada and colleagues, the strategy of ATO induction followed by autologous stem cell transplantation in the high fraction of patients who are rendered negative for the PML/RAR alpha transcript by an assay with a sensitivity of 10-4 can also produce long-term DFS in 65% in patients with APL in relapse.
Importantly, central nervous system prophylaxis with intrathecal chemotherapy and high-dose cytarabine used in mobilization was part of the regimen. This is consistent with other reports of autotransplant in this setting. It is not known whether all patients who become polymerase chain reaction (PCR) negative need autotransplant, as some patients in the original ATO papers had prolonged DFS without transplant. It is also unknown whether the hopefully small number of patients who relapse from current arsenic induction regimens would benefit from this approach or whether they would require chemotherapy regimens to become PCR negative before transplant.
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