Outcomes in Acute Lymphoid Leukemia Patients with Incomplete Hyper-CVAD Cycles

Introduction: Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) is a commonly used regimen in acute lymphoblastic leukemia (ALL) for a total of 4 A/B intensive courses. This regimen is often limited due to multiple complications including organ dysfunction and medication toxicities along with high rates of relapse or disease progression. Prior studies have indicated five-year overall survival (OS) of 39% with severe prolonged myelosuppression being a common complication. In one study 6% of patients died during induction therapy. Here we provide clinical outcomes of non-transplanted patients with ALL receiving hyper-CVAD regimen in our tertiary referral center. We assessed overall survival, mortality rates, and complications during induction therapy with hyper-CVAD in our cohort of adult patients. Methods: We conducted a comprehensive, retrospective study at our center, evaluating outcomes of non-transplant eligible ALL patients treated from February 2003 to October 2022. We excluded patients without all available diagnostic information, and those who underwent allogeneic stem cell transplantation (SCT). We classified the patient based on their BCR - ABL1 gene status. Groups were subcategorized by highest cycle of Hyper-CVAD completion, with reason for cessation (medication toxicity/organ dysfunction, lost to follow up, progressive disease/relapse) elicited for those who did not complete all treatment cycles. Overall survival was analyzed using T-Test, ANOVA and Bartlett's test. Statistics are descriptive and our institutional review board approved this retrospective study. Results: We report outcomes of 43 ALL patients who did not undergo SCT. Median age at diagnosis was 52 years (range of 18-71 years). 33/43 (76.7%) patients received Hyper-CVAD regimen. 2/33 (6.1%) completed the entire course through 4B. 12 (36.3%) out of 33 patients received less than cycle 3b; 21/33 (63.6%) received at least cycle 3b. 2/6 (33.3%) completed up to cycle 1B, 2/11 (18.2%) completed up to cycle 2B, 13/25 (52%) completed up to cycle 3B, and 2/33 (6.1%) completed up to cycle 4B. 12/33 (36.4%) of patients were not able to complete more than cycle 3A due to organ dysfunction and intolerance, being lost to follow up, progressive disease or relapse, or participation in a trial. For the patients who received less than cycle 3b, the reasons for early discontinuation were: organ dysfunction 6/12 (50%), progressive disease or relapse 3/12 (25%