Treatment outcomes for older adults with B cell acute lymphoblastic leukemia (B cell ALL) are poor, partially because of poor tolerance to intense chemotherapy. Information on patient experience-an important consideration in drug development-is lacking. We investigated the signs, symptoms, and impacts of B cell ALL on older patients (or those with comorbidities that may reduce chemotherapy tolerance).This observational study involved teleconference-based, qualitative, semi-structured interviews with patients newly diagnosed with B cell ALL, aged ≥ 55 years, or 30-54 years with ≥ 1 comorbidity. Participants described their B cell ALL experience, including signs, symptoms, and impacts, and how bothersome/disturbing these were from 0 (not at all) to 10 (greatly) at three timepoints (around diagnosis, at worst, and at interview). Salient signs/symptoms were those reported by ≥ 40%, with average disturbance ratings of ≥ 4. A conceptual model of key disease- and treatment-related signs, symptoms, and impacts was developed.Interviews with 20 participants (mean age 57.9 years; 80% diagnosed within 18 months) revealed 63 signs/symptoms and 37 impacts. All reported fatigue-related symptoms, and most reported gastrointestinal (n = 18, 90%), central/peripheral nervous system (n = 16, 80%), and pain-, respiratory-, blood-, and mouth-related (all n = 14, 70%) symptoms. Eight signs/symptoms were salient around diagnosis (fatigue, tiredness, weakness, exhaustion, shortness of breath, sweating, general pain, and diarrhea) and 16 were salient "at worst"; four remained salient at interview (all fatigue-related). All participants reported emotional impacts, and most reported physical and social impacts (both n = 16, 80%). The most frequent impact was inability to do previous hobbies/activities (n = 15, 75%), followed by decreased ability for activities of daily living and worry/fear/nervousness (both n = 12, 60%).This study provides insight into patients' experience with newly diagnosed B cell ALL among older patients or those with clinically significant comorbidities. This enhances understanding of what matters most to patients and informs future treatment development and clinical care.