Abstract
Background: Comorbid conditions have an effect on outcomes in many diseases. Acute promyelocytic leukemia (APL), a subtype of AML, is highly curable with a long term survival rate as high as 90% in large clinical trials treated on a protocol. However survival in the general population is much lower with an induction mortality of 30%. A high comorbid index has been linked to increased mortality and decreased survival in several hematologic malignancies including AML, MDS, CML, multiple myeloma and NHL. There is published data on older patients with APL and exclusion due to poor health or multi-morbidity but there is inadequate literature on how comorbid conditions impact induction mortality in APL.
Hypertension and obesity are prevalent in >30% of Georgia (GA) and South Carolina (SC) residents according to 2014 CDC data, and these and other conditions were prevalent among our patient population. We sought to quantify comorbidities in patients with newly diagnosed APL and assess if it had an effect on early death.
Methods: We performed a retrospective chart review with IRB approval of 138 patients treated at leukemia treatment hospitals in GA, SC and neighboring states. These centers had access to a simple two-page APL treatment algorithm we developed as well as expert support. We used the Combined Age-Charlson Comorbid Index (CA-CCI), a tool utilized as a measure of mortality risk based on comorbidity which accounts for age as an independent risk factor for mortality, assigning additional points for age ≥50. The CCI assigns weights of 1-6 to comorbidities including but not limited to hypertension, Type II diabetes, renal impairment and then an overall score is calculated; the higher the score, the higher the mortality risk. We also tracked obesity as a separate condition, as it is not included in the CCI. Statistics are descriptive and survival analysis was performed by SPSS version 24; overall survival curves were obtained by Kaplan-Meier analysis.
Results: Between 7/2013 and 4/2017, 138 patients were treated at 4 large leukemia centers and 30 community hospitals. 129 (93%) patients had one or more comorbid conditions, excluding age. Obesity was the most prevalent (n=85, 62%), followed by hypertension (n=75, 54%). Based on the CA-CCI calculation, 24.64% (n=34) had a score of 2-3, 14.49% (n=20) had a score of 4, and 23.91% were highest risk with a score of ≥5 (n=33). The remaining 36.96% (n=51) had a risk score of ≤1 (lowest risk).
There were 12 induction deaths (8.7%). Of these, two patients were lowest risk with a score of ≤1, five scored 2-3, one scored 4, and four were highest risk with a score ≥5. Eight of the 12 patients who died were obese. Overall, we found our induction mortality rate of 8.7% to be low compared to nationally published data in APL.
Conclusion: Patients treated for APL in GA, SC and neighboring states from 2013-2017 had a high incidence of comorbid conditions at presentation. We felt it was important to also highlight that a majority had concomitant obesity, a comorbidity linked to poor prognosis in many diseases including APL. In spite of the majority of our patients having multiple comorbidities and nearly a quarter having a CA-CCI score of ≥5, our induction mortality was low. Given our relatively small number of deaths, we believe that in APL patients with multiple comorbid conditions, our treatment algorithm combined with expert support has decreased induction mortality.
Arellano: Cephalon Oncology: Research Funding. Kota: Pfizer: Consultancy; Incyte: Consultancy; Xcenda: Consultancy; Novartis: Consultancy; Takeda Pharmaceuticals: Consultancy; Leukemia Lymphoma Society: Research Funding.
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