A Patient-Reported Outcome Measure for Symptoms and Symptom Burden of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Authors: Williams Loretta A. , Garcia-Gonzalez Araceli , Ahaneku Hycienth O. , Cortes Jorge E. , Garcia-Manero Guillermo , Kantarjian Hagop M. , Mendoza Tito R. , Shi Qiuling , Borthakur Gautam , Burger Jan A. , Jabbour Elias J. , Takahashi Koichi , Lin Huei K. , Limaye Achala , Cleeland Charles S. 
Published: October 2019

Background: Patient report of disease- and treatment-related symptom burden in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is scarce. Symptom burden is the combined impact of disease and treatment symptoms on daily functioning. Lack of recognition and monitoring of symptoms and symptom burden can lead to inadequate management and possible treatment non-adherence.

Aims: Our aim is to develop a short, valid, reliable patient-reported outcome measure of symptoms and symptom burden experienced by AML and MDS patients and to determine the validity of a single measure for research and practice.

Methods: After obtaining IRB approval, patients with AML (N=152) and MDS (N=97) were recruited to this cross-sectional study. Patients rated the 13 core symptom items (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, trouble remembering, lack of appetite, drowsiness, dry mouth, sadness, vomiting, and numbness and tingling), 6 proposed AML/MDS symptom items (muscle weakness, malaise, fever, headache, diarrhea, skin problems), and 6 interference items (general activities, mood, work, relations with others, walking, and enjoyment of life) of the MD Anderson Symptom Inventory (MDASI) on 0-to-10 scales (0 = not present or no interference; 10 = as bad as can be imagined or complete interference) twice 1-2 days apart. Clinical and demographic information was collected from medical records and analyzed using descriptive statistics. Means of the symptom and interference ratings for the AML and MDS patients were compared using T-tests. Standard psychometric techniques were used to determine the reliability, stability, and validity of the instrument in patients with AML and MDS.

Results: All MDS patients were outpatients while 75 of the AML patients were inpatients and 77 were outpatients. The AML and MDS patients had been diagnosed a mean of 13.8 months (standard deviation [SD]=23.9) and 30.5 months (SD=32.4) respectively. The mean (Mn) symptom and interference ratings respectively for the AML inpatients (Mn=2.8, SD=1.6; Mn=4.0, SD=2.4) were significantly higher than for the AML outpatients (Mn=1.8, SD=1.4, p<0.01; Mn=2.7, SD=2.3, p<0.01) or MDS patients (Mn=1.9, SD=1.5, p<0.01; Mn=2.7, SD=2.5, p<0.01). The mean ratings for the 5 most severe symptom means for AML and MDS patients respectively were: fatigue (Mn=4.0, SD=2.8; Mn=4.0, SD=2.5; p =0.97), disturbed sleep (Mn=3.3, SD=3.2; Mn=2.7, SD=3.3; p=0.19), drowsiness (Mn=3.0, SD=2.8; Mn=2.8, SD=3.1; p=0.70), muscle weakness (Mn=2.9, SD=2.8; Mn=2.9, SD=3.0; p=0.91), dry mouth for AML patients (Mn=3.4, SD=3.2; Mn=2.2,SD=2.8; p<0.01), and shortness of breath for MDS patients (Mn=2.7, SD=2.8; 1.9, SD=2.3; p=0.02). Two of the 6 AML/MDS symptom items (fever and headache) were dropped because so few patients said they experienced the symptoms at more than a mild (0-4 rating) level (12% and 11% respectively). Both groups of patients endorsed similar symptoms, and none of the means of the 4 final AML/MDS symptoms were significantly different between the groups. Cronbach's reliability for all symptom items for AML and MDS respectively were 0.88 and 0.91 and for all interference items were 0.86 and 0.92. The test-retest reliability intra-class correlations were 0.85 for the core symptoms, 0.77 for AML/MDS symptoms, and 0.84 for the interference items. The MDASI-AML/MDS can be completed by patients in less than 5 minutes.

Conclusion/Summary: Lack of recognition of symptoms experienced by patients with AML and MDS can lead to inadequate management of symptoms, interfere with the ability of patients to function and enjoy life, and impact the tolerability of and adherence to treatment regimens. While the symptoms experienced by the two groups had some variation in severity, a similar group of symptoms were the most common and relevant for both groups of patients, and the same measure was appropriate for both groups. The MDASI-AML/MDS is a brief, easily-completed, and validated measure of symptom burden for patients with AML and MDS that can be used for accurate and consistent monitoring of symptoms by clinicians and researchers.

Disclosures

Williams: Amgen: Consultancy; Novartis: Research Funding. Cortes:Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BerGenBio AS: Research Funding; Teva: Research Funding; Ariad: Consultancy, Research Funding; Astellas: Consultancy, Research Funding; Ambit: Consultancy, Research Funding; Arog: Research Funding; Celator: Research Funding; Jenssen: Consultancy. Mendoza:Amgen Inc.: Consultancy. Shi:Amgen Inc.: Consultancy. Cleeland:Amgen Inc.: Consultancy.