Background: The recurrent detection of the PML- RARα transcripts in APL patients in complete remission (CR) is predictive of clinical relapse. Intervention at the time of molecular relapse rather than at the time of overt clinical relapse may minimize the risks associated with the disease as well as treatment-related complications. Previous studies have shown that patients treated at molecular relapse had improved overall survival compared to patients treated at clinical relapse; however, the optimal approach to the treatment of molecular relapse has not yet been established. Arsenic trioxide is active as a single agent in APL patients who developed overt clinical relapse after treatment with ATRA and anthracycline chemotherapy. We evaluated the use of single agent arsenic trioxide in APL patients who are still in first hematological CR but have become RT-PCR positive.

Methods: So far, 2 patients were studied, both females with the long form of RAR RARα (bcr1), aged 29 and 39 years. These patients had normal bone marrow morphology but were found to be RT-PCR positive twice in an interval of at least 2 months, while in first CR at 12 and 36 months, respectively. Arsenic trioxide, 0.15 mg/kg/dose, was administered intravenously for 5 days per week for 5 weeks (total of 25 doses) with a 3 to 6 week rest period between cycles up to a maximum of 4 cycles.

Results: Both patients became PCR negative after the first cycle of arsenic trioxide. One patient completed four cycles of therapy. The second patient had a history of diabetes mellitus, received only 20 doses of the first cycle and was removed from the study because of grade III sensory neurotoxicity. The only other side effects were grade II headache in both patients and self-limited grade III liver toxicity in one patient. Both patients remain RT-PCR negative at 30 and 28 months after enrollment, respectively, without further therapy.

Conclusions: Without treatment, these patients could be expected to have developed a clinical relapse within 4–10 months. Arsenic trioxide induced a durable second molecular relapse, extending disease-free survival and obviating the need for more intensive treatment, such as chemotherapy and stem cell transplantation.

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