Acute Myeloid Leukemia and Cirrhosis: Trends in Utilization of Induction Chemotherapy, Rate of Hospitalizations and Mortality

Introduction: The presence of underlying cirrhosis poses a serious challenge in treatment of newly diagnosed acute myeloid leukemia (AML) patients. In current practice, patients with significant hyperbilirubinemia are precluded from optimal induction and consolidation therapy. Allogenic stem cell transplant is also not a viable option for these patients. This is the first study aimed at evaluating the safety and trends of utilization of chemotherapy in subset of patients with newly diagnosed AML and comorbid cirrhosis, using the Nationwide Inpatient Sample.

Methods: We designed a retrospective study using the Nationwide Inpatient Sample (NIS) data, the largest US inpatient database which includes approximately 76 million patients from 2005 to 2014. The authors identified hospitalizations for induction chemotherapy using the primary discharge diagnosis of 'encounter for chemotherapy' (ICD-9 codes -V58.1, V58.11 and V58.12) or procedure codes for 'administration of antineoplastic agent' (0010, 0015, 9925, 9928) and a secondary diagnosis of acute myeloid leukemia, myeloid sarcoma or acute monocytic leukemia. We excluded patients with relapsed disease or in remission. Amongst this population, patients with a diagnosis of cirrhosis including alcoholic, non-alcoholic and biliary cirrhosis were examined to find the differences in baseline characteristics, annual trends in the number of hospitalizations for chemotherapy and total hospitalization charges. We used logistic regression to calculate the adjusted odds ratios (aOR) for in-hospital mortality among these patients.

Results: Between 2005 and 2014, a total of 514,032 admissions were identified with a primary diagnosis of chemotherapy for AML. A total of 1,310 (0.25%) admissions had an underlying diagnosis of cirrhosis. The number of hospitalizations for induction chemotherapy in patients with cirrhosis and AML had a statistically significant increase from 62 in 2005 to 195 in 2014. Interestingly, hospitalization for AML patients without cirrhosis has remained largely constant with 52,673 AML patients admitted in 2005 and 55,925 in 2014 (5.8% increase). In-hospital mortality in patients with cirrhosis and undergoing induction chemotherapy for AML was 14.5% (n=9) in 2005, decreasing to almost half at 7.1% in 2014 (n=14). In-patient mortality for AML patients without cirrhosis undergoing chemotherapy has also decreased, from 4.18% (n=2,205) in 2005 to 3.91% (n=2,190) in 2014. Patients with AML and cirrhosis were less likely to undergo treatment at academic centers (81.8%) than those without cirrhosis (87.1%, p=0.046), and they were less likely to possess private insurance (39.3% vs 33.3%, p=0.000). Mortality rate was higher in patients with AML and cirrhosis (12.2%, n=161) than in those without cirrhosis (4.5%, n=23369). The adjusted odds ratio for mortality in patients with cirrhosis was 2.01 (p=0.001), with older age (p=0.00) and caucasian race (p=0.01) being significant confounders. Average hospital cost for each admission for patients with AML and cirrhosis was ($223,723.6±$16,169), significantly higher than for those without cirrhosis ($129,383).

Conclusions: Our study highlights the fact that the management of patients with AML and cirrhosis continues to be a dilemma. With the advances in chemotherapy over the last decade, there has been a positive trend with an increase in the number of hospitalizations for induction chemotherapy in patients with AML and cirrhosis as well as a decrease in mortality. However, the pace of improvement remains slow. Moreover, since cirrhosis is more prevalent in the lower socioeconomic strata, these patients are less likely to have private insurance or receive treatment at an academic center, which may contribute to suboptimal care. The increase in mortality in patients with AML and cirrhosis compared to those without cirrhosis can be explained by a compounding effect of AML on pre-existing complications of cirrhosis, such as coagulopathy, thrombocytopenia, encephalopathy, malnutrition and perturbed drug metabolism. Besides, hepatic dysfunction and hyperbilirubinemia often require chemotherapy dose reduction with preclusion of curative options. Further research is needed to develop standard guidelines and non hepatotoxic chemotherapeutic agents.