Long Term Trends in Chronic Myeloid Leukemia (CML) Following the FDA Approval of Tyrosine Kinase Inhibitors (TKIs), on Bone Marrow Transplant Rates and Clinical Outcomes - a Study of the Nationwide Inpatient Sample Between 1998-2011

Abstract

Background: Single-institution and international, retrospective studies have demonstrated a decrease in the number of allogeneic stem cell transplants (alloSCTs) in patients with CML in the first few years after the introduction of TKIs. However alloSCT remains the only curative therapy in patients who develop resistance to multiple TKIs, and in those who present with blast crises. The long-term impact of TKIs on the trend of SCTs in the United States in CML remains unexplored. Therefore, we sought to examine the trend in the number of SCTs, as well as the mortality and clinical complications for CML over the decade following the FDA approval of Imatinib.Methods: We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (NIS) between 1998 and 2011 using the ICD-9 code 205.1 for CML in the primary and secondary diagnosis fields. Only patients 18 years or older were included in the analysis. We monitored the trends in allo-SCT, mortality and clinical complications related to CML. A p value of <0.05 was considered significant. We have also attempted to analyze the trends in cost and length of hospitalization during this decade. Cost of hospitalization was adjusted for inflation in reference to the year 2011 and cost to charge ratio.Results: A total of 53254 (weighted n=262964) hospitalizations for CML (Male 54.6% and average age 65.9+/-0.8 yrs) occurred from 1998-2011. There has been a 408% decrease in the rate of transplants and 79.9% decrease in in-hospital mortality since the introduction of TKIs (p<0.0001). There has also been a 48.3% reduction in the average length of hospital stay, despite which there has been a 17% increase in cost of hospitalizations for CML (p<0.0001). There have also been marked reductions in the complications related to CML with the advent of TKI therapy. There has been almost 200% reduction in blast crises (p<0.0001), a 120.8% decrease in splenic infarct/splenic vein thrombosis (p<0.0001), 56.1% reduction in epistaxis (p <0.0004).Conclusion: This analysis supports the widely held belief that the introduction of TKIs has not only reduced the reliance on allogeneic transplants, but has also led to remarkable improvement in mortality and CML related complications. Increase in cost of hospitalization could be related to the overall increase in health care cost, 4.5% yearly from 1998-2000, 3.9% from 2000-2007 and 1.8% 2007-2010. DisclosuresNo relevant conflicts of interest to declare.