Emotion And Symptom-focused Engagement (EASE): a randomized phase II trial of an integrated psychological and palliative care intervention for patients with acute leukemia
We designed a novel, manualized intervention called Emotion And Symptom-focused Engagement (EASE) for acute leukemia (AL) and report here on a phase II randomized controlled trial (RCT) to assess its feasibility and preliminary efficacy.
Patients were recruited within 1 month of hospital admission and randomized to EASE plus usual care (UC) or UC alone. EASE includes (1) EASE-psy, a tailored psychotherapy delivered over 8 weeks, and (2) EASE-phys, weekly physical symptom screening over 8 weeks to trigger early palliative care. The primary outcome was traumatic stress symptoms; secondary outcomes included physical symptom burden and quality of life. Assessments were conducted at baseline and at 4, 8, and 12 weeks. Between-group differences were evaluated using multilevel modeling.
Forty-two patients were randomized to EASE (n = 22) or UC (n = 20), with 76% retention at 12 weeks. Predefined feasibility outcomes were met: 86% (19/22) of EASE participants completed ≥ 50% of EASE-psy sessions (goal ≥ 64%); 100% received Edmonton Symptom Assessment System (ESAS, modified for AL) screenings, 64% (14/22) of whom completed ≥ 50% of planned screenings (goal ≥50%); and 100% with scores ≥ 4/10 on any physical ESAS-AL item had ≥ 1 meeting with the EASE-phys team (goal 100%). Significant treatment-group differences favoring EASE were observed in traumatic stress symptoms at 4 and 12 weeks, and pain intensity and interference at 12 weeks (all p < .05).
EASE is feasible in patients newly diagnosed with AL and shows promise of effectiveness. These results warrant a larger RCT to provide evidence for its more routine use as a standard of care.
KeywordsHematology Cancer Acute leukemia Traumatic stress Psychosocial intervention Early palliative care
GR holds the University of Toronto/University Health Network Harold and Shirley Lederman Chair in Psychosocial Oncology and Palliative Care, and CZ holds the Rose Family Chair in Supportive Care from the University of Toronto. The authors would like to thank the clinical, research, and administrative staff who contributed to this project, especially the hematology staff, including clinical associates Drs. Andrzej Lutynski, Amr Rostom, and Dina Khalef; our EASE-phys palliative care treatment team, including Patricia Murphy-Kane, Kelly McGuigan, Jocelyn Brown, Christine Cameron, and Drs. John Bryson, Ernie Mak, Breffni Hannon, and Ahmed Al-Awamer; and our research staff and students, including Abigail Magpayo, Sarah Watt, Ekaterina An, Erica Wennberg, Beth Edwards, Amy Deckert, Loreto Fernandez, Dorothy Wong, and Ina Delphra. We are especially grateful to our study participants and their families who gave their time and effort to help us better understand the experience of living with acute leukemia.
Conception and design: GR, CZ, with contributions from CM, CL, AR, AS, and CMM
Administrative support: CM, AR
Provision of study materials or patients: AS
Trial implementation, acquisition, and assembly of data: CM
Analysis and interpretation of data: KM, CM, CL, GR, CZ, AR
Manuscript writing: All authors
Final approval of manuscript to be published: All authors
This trial was funded by the Canadian Cancer Society Research Institute (CCSRI grant no. 702603; GR and CZ, Co-Principal Investigators). This research was also supported in part by the Princess Margaret Cancer Centre and Princess Margaret Cancer Foundation, University Health Network, Toronto, Ontario, Canada, and the Ontario Ministry of Health and Long-term Care.
Compliance with ethical standards
This pilot trial received approval from the University Health Network (UHN) Research Ethics Board (REB No. 13–6631-CE) and was monitored by the UHN Data Safety Monitoring Board. Informed consent was obtained from all individual participants included in the study. The trial was registered with ClinicalTrials.gov (Identifier: NCT02353559).
Conflict of interest
AS reports personal fees and grants outside this submitted work from Novartis, Takeda Pharmaceuticals, Otsuka Pharmaceutical, Jazz Pharmaceuticals, Medivir, and Abbvie. The remaining authors declare no conflicts of interest.
The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The Co-Principal Investigators had full access to all study data and had final responsibility for the decision to submit for publication. They agree to allow the journal to review the data if requested. This manuscript contains original material.
- 1.O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, Bhatt V, Bixby D, Blum W, Coutre SE, de Lima M, Fathi AT, Fiorella M, Foran JM, Gore SD, Hall AC, Kropf P, Lancet J, Maness LJ, Marcucci G, Martin MG, Moore JO, Olin R, Peker D, Pollyea DA, Pratz K, Ravandi F, Shami PJ, Stone RM, Strickland SA, Wang ES, Wieduwilt M, Gregory K, Ogba N (2017) Acute Myeloid Leukemia, Version 3.2017, NCC Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw 15(7):926–957CrossRefGoogle Scholar
- 7.DuHamel KN, Mosher CE, Winkel G Labay LE, Rini C, Meschian YM, Austin J, Greene PB, Lawsin CR, Rusiewicz A, Grosskreutz CL, Isola L, Moskowitz CH, Papadopoulos EB, Rowley S, Scigliano E, Burkhalter JE, Hurley KE, Bollinger AR, Redd WH (2010) Randomized clinical trial of telephone-administered cognitive-behavioral therapy to reduce post-traumatic stress disorder and distress symptoms after hematopoietic stem-cell transplantation. J Clin Oncol 28(23):3754–3761CrossRefGoogle Scholar
- 10.Rodin G, Lo C, Rydall A, Shnall J, Malfitano C, Chiu A, Panday T, Watt S, An E, Nissim R, Li M, Zimmermann C, Hales S (2018) Managing Cancer And Living Meaningfully (CALM): a randomized controlled trial of a psychological intervention for patients with advanced cancer. J Clin Oncol 36(23):2422–2432. https://doi.org/10.1200/JCO.2017.77.1097 Open accessCrossRefPubMedPubMedCentralGoogle Scholar
- 13.El-Jawahri A, LeBlanc T, VanDusen H, Traeger L, Greer JA, Pirl WF, Jackson VA, Telles J, Rhodes A, Spitzer TR, McAfee S, Chen YA, Lee SS, Temel JS (2016) Effect of inpatient palliative care on quality of life 2 weeks after hematopoietic stem cell transplantation: a randomized clinical trial. JAMA 316(20):2094–2103CrossRefGoogle Scholar
- 17.Rodin G, Fitzgerald P, Nissim R, Marmar C, Zimmermann C. Emotion And Symptom-focused Engagement (EASE) Treatment Manual: an intervention for individuals with acute leukemia. Canadian Intellectual Property Office. Date of issue: 2015-09-08; Filing date: 2015-09-04; Copyright #: 1124207Google Scholar
- 18.Princess Margaret Cancer Centre, University Health Network: online reference: http://www.uhn.ca/PrincessMargaret. Website accessed January 8, 2019
- 23.Hannon B, Swami N, Pope A, Rodin G, Dougherty E, Mak E, Banerjee S, Bryson J, Ridley J, Zimmermann C (2015) The oncology palliative care clinic at the Princess Margaret Cancer Centre: an early intervention model for patients with advanced cancer. Support Care Cancer 23(4):1073–1080CrossRefGoogle Scholar
- 24.Rodin G (2009) Individual psychotherapy for the patient with advanced disease. In: Chochinov HM, Breitbart W (eds) Handbook of Psychiatry and Palliative Medicine, Second edn. Oxford University Press, London, pp 443–453Google Scholar
- 25.Marmar C, Henn-Haase C (2011) Anxiety Reduction Treatment for Acute Trauma (ARTAT): Treatment Manual. New York University, New YorkGoogle Scholar
- 27.Cancer Care Ontario: Symptom Management Guides to Practice. Website accessed September 1, 2017. Available at: https://www.cancercare.on.ca/toolbox/symptools/
- 28.Cardeña E, Koopman C, Classen C, Spiegel D (1996) Review of the Stanford Acute Stress Reaction Questionnaire (SASRQ). In: Stamm BH (ed) Measurement of stress, trauma and adaptation. Sidran Press, Lutherville, pp 293–297Google Scholar
- 35.Beck AT, Steer RA, Brown GK (1996) Manual for the Beck Depression Inventory-II. Psychological Corporation, San AntonioGoogle Scholar
- 39.Cohen J (1988) Statistical Power Analyses for the Behavioral Sciences, 2nd edn. Lawrence Erlbaum, HillsdaleGoogle Scholar
- 42.Lo C, Hales S, Chiu A, Panday T, Malfitano C, Jung J, Rydall A, Li M, Nissim R, Zimmermann C, Rodin G (2016) Managing Cancer And Living Meaningfully (CALM): randomized feasibility trial in patients with advanced cancer. BMJ Support Palliat Care. Published Online First: 19 January 2016. https://doi.org/10.1136/bmjspcare-2015-000866 CrossRefGoogle Scholar
- 44.Ferrell BR, Temel JS, Temin S, Alesi ER, Balboni TA, Basch EM, Firn JI, Paice JA, Peppercorn JM, Phillips T, Stovall EL, Zimmermann C, Smith TJ (2017) Integration of palliative care into standard oncology care: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 35(1):96–112CrossRefGoogle Scholar