Arsenic Trioxide (ATO) as Induction Therapy Achieves Early Complete Cytogenetic Remission In Acute Promyelocytic Leukemia (APL)

All Trans Retinoic Acid (ATRA) with chemotherapy, though an effective induction therapy for newly diagnosed APL, is associated with significant morbidity and mortality in our population. In order to reduce toxicity without compromising efficacy, we treated 53 consecutive patients of newly diagnosed APL with single agent ATO as induction therapy. Minimum toxicity with excellent efficacy emerged from such an approach reiterating ATO's niche in frontline management of APL.

Newly diagnosed APL patients presenting to our centre were treated immediately at diagnosis with infusional ATO (10mg/day for 45 days). They were monitored for toxicity and evaluated for morphological and cytogenetic remission at the end of 45 days. This was followed by planned consolidation with ATRA (45mg/m2 × 60 days) plus Daunomycin (60mg/m2, 3 doses × 3 cycles) sequenced by standard maintenance with ATRA for 18 months.

Fifty three consecutive patients from May 2008 to May 2010 received induction with ATO. These included Low risk (n= 10), intermediate risk (N=18),and high risk (n=25). Four patients died within first week of diagnosis and were non evaluable. Amongst the 49 evaluable patients one died in induction phase due to neutropenic sepsis. No overt differentiation syndrome was encountered though 17 patients needed short course of steroids for weight gain. Twenty eight patients developed febrile neutropenia warranting antibiotics alone while 7 patients needed antifungals too. 2 patients had to be discontinued from ATO due to persistent QT prolongation on EKG. Median duration of hospital stay was 17 days (range 3 to 46 days). Response evaluation by cytogenetic remission status was not available in 5 patients. In the remaining (n=44), 43 achieved morphological and complete cytogenetic remission at the end of induction therapy while all were in cytogenetic remission after consolidation. One patient died in maintenance due to unrelated septic shock while still being in remission. All patients have either completed or are currently on maintenance phase at a median follow up of 17 months (range 2 to22 months). ATO was active across all risk groups with nearly all achieving complete cytogenetic response post induction treatment. Transfusion requirements, hospital stay and antibiotic use were modest as compared to our previous institutional data.

ATO induction therapy is a suitable, effective and well tolerated regimen for newly diagnosed APL across all risk groups in our population. Complete cytogenetic remission with minimum toxicity was achieved in almost all patients after induction. However, longer follow up is required to gauge the impact of early cytogenetic response with regards to cure in APL.Future studies are aimed at decreasing doses of anthracyclines in low and intermediate risk groups.

No relevant conflicts of interest to declare.