Early life-threatening complications are a hindrance towards the cure of acute promyelocytic leukemia (APL). Patients with increased WBC count could indicate severe symptoms in line with cytokine storms at admission or along with induction therapy.
To determine the safety and efficiency of a WBC reduction centered approach, we designed this cocktail regimen and enrolled 55 patients with a medium follow-up time of 39 months (15 - 72 months). In brief, the induction started with ATRA (25mg/m2/day), arsenic trioxide (0.15mg/kg/day), and dexamethasone (5mg/day). The dexamethasone was started at the same time as the application of ATRA and tapered down when WBC count decreased for three consecutive days and withdrawal within one week after that. When the WBC>2*109/L at presentation, hydroxyurea was given (1.5g; q6h). The withdrawal criteria were i) WBC decreased three consecutive days after reaching the highest peak and ii) WBC<10*109/L. If the WBC was not reduced after using hydroxyurea for three days, a cocktail of mitoxantrone (4mg/m2) plus cytarabine (50mg/m2) (MA) was applied. The withdrawal of criteria of MA was i) WBC decreased three consecutive days after reached the highest peak or ii) WBC<10*109.
Our strategies helped to keep patients from the situation of with either neutrophil deficiency or hyperleukecytosis maintain WBC between two and 20*109/L. Supportive care included keeping the platelets at a level of 20-30*109/L and fibrinogen >1.5g/L. Our results from induction indicated lower myelosupression, differentiation syndrome and severe bleeding events. The consolidation began at four weeks after the end of induction. It contained four weeks of an on and off schedule of arsenic trioxide (0.15mg/kg/day), in total four cycles, and two weeks of an on and off schedule of ATRA (25mg/m2/day), in total seven cycles. A total of eight intrathecal injections were given on the first and last day of arsenic trioxide.
No early death was observed through our strategy during the induction. All patients reached hCR by the end of induction. Relapse-related death occurred in four out of 55 patients (7%), and there was no treatment-related mortality. All the relapsed patients entered CR again after using the same protocol. Grade 3-4 adverse events were observed among 12% of all the cases. Three-year probability of overall survival (pOS) was found to be 100%. Our cocktail strategy focus of reducing WBC count is considered the key to trigger the cytokine storm cascade and sheds new light on maximally eliminating early mortality of APL patients.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
