Background: Individuals diagnosed with AL may experience severe physical and psychological distress due to the illness and its treatment, the threat of relapse and treatment failure, and a high risk of mortality. To alleviate psychological and physical distress in this population, we developed a novel, 8-week, manualized intervention called EASE. This includes: 1) EASE-psy- a tailored psychotherapeutic component to reduce psychological distress; and 2) EASE-phys-symptom screening, with moderate to severe physical symptoms triggering early palliative care. Methods: To assess the feasibility and preliminary efficacy of EASE, patients were recruited within 2 weeks of admission to a comprehensive cancer center and randomized to receive either EASE or usual care (UC). Physical and psychological symptoms were assessed at baseline, 4, 8 (primary endpoint), and 12 weeks. Intervention patients received 6-10 psychotherapy sessions over 8 weeks, weekly assessment of physical symptoms, and consultation and follow-up by palliative care, when needed. One-way ANOVA was performed to assess mean change scores over time between groups. Results: Forty-two patients were randomized to EASE (n = 22) or UC (n = 20). Predefined feasibility outcomes were all met: > 86% (19/22) of EASE participants (goal > 64%) completed > 50% of proposed EASE-psy sessions; 64% (14/22) completed symptom screenings (goal > 50%); and 100% of those with moderate to severe symptoms had > 1 meeting with the EASE-phys team (goal 100%). There were statistically significant findings favoring EASE vs. UC for satisfaction with care at 8 and 12 weeks (Δ: -3.12 vs 7.39, p < 0.04; -6.1910 vs 0.0125 p < 0.03). There were trends favoring EASE vs. UC for traumatic stress symptoms, depressive symptoms, quality of life, attachment security, and number, severity, and distress related to physical symptoms at 4, 8, and 12 weeks. Conclusions: Although not powered for statistical significance, this randomized pilot trial of EASE for AL showed promising reductions in psychological and physical distress and supports the feasibility and need for a larger randomized controlled trial. Clinical trial information: NCT02353559