Weight Gain during Induction Therapy of Acute Promyelocytic Leukemia Patients: A Preventable Problem

Introduction:

Differentiation syndrome can be a major complication of all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) therapy in acute promyelocytic leukemia (APL) patients. The incidence of DS in studies varies widely and reported between 2-27% mainly due to the definition used for the diagnosis of DS. Dyspnea, unexplained fever, weight gain greater than 5 kg, unexplained hypotension, acute renal failure, and presence of infiltrates and/or pleural, pericardial effusions on chest radiographs are regarded as the signs and symptoms associated with DS. Four or more of these criteria is required for a diagnosis of severe DS but any single criteria is not diagnostic. Weight gain of 5 kg is seen in up to 38% of moderate DS (2-3 criteria) and 68% of severe DS patients. APL patients characteristically have a bleeding tendency at presentation requiring aggressive transfusion support that leads to fluid overload and weight gain unless meticulously monitored. Herein we report our observations with weight gain in APL patients during induction period.

Methods:

Chart review of APL patients managed between 01/2006 and 04/2017 was conducted and patients who gained more than 5kg from baseline at admission were identified. Patients from 09/2013 to 04/17 were managed on an algorithm designed to reduce induction mortality in APL patients and care was provided by physicians dedicated to the management of this disease. The outcomes in these patients was compared to those prior to implementation of the algorithm. The algorithm was a two-page set of guidelines directed at preventing or treating the major causes of early death including meticulous monitoring of the weight as well as aggressive diuresis in the event of weight gain. Institutional review board approval was obtained. for this review.

Results:

130 patients were managed during this time period. 57 patients (trial group TG) were managed on the algorithm while 73 (pre-trial, PG) were managed prior to this implementation. Median age was higher in trial patients 48 vs 45 years, range being 21-81 in TG vs 19-80 in PG. Median WBC was (4.2 vs 2.7) and high risk (WBC > 10,000/mm3) were higher in the PG vs TG. Median platelet counts were similar. The predominant induction combination was ATRA with chemotherapy in PG (66%) whereas ATRA/Arsenic combination was used in the TG (75%). Median weight gain in the TG was less than PG. (3.15 vs 3.5 kg, range 0-12.8kg vs 0-35 kg). 3 patients in the PG and 1 in the TG did not get treatment and were discharged with comfort care. Excluding these patients, 26 % of patients in TG and 38% in PG gained more than 5kg. The mortality was higher in the PG group at 38% in those that gained more than 5 kg compared to 20 % in the TG. In contrast, the mortality was lower in both TG and PG patients with weight gain <5 Kg at 7.1% and 7.4%. Five patients in the PG group did not have follow up weights checked but there was documentation that would satisfy definition of severe DS and all 5 patients died between 4-14 days after admission. The incidence of severe DS was also lower in trial patients ( 6% vs 18%).

Conclusions:

Management of APL patients utilizing an algorithm might lead to better monitoring of complications like weight gain and preventing fluid overload seen during the treatment of APL. The impact of the weight gain on outcomes in comparison to other variables that might impact survival in our cohort will be evaluated further.