Pre-phase Cyclophosphamide in High-risk Aggressive Lymphomas: A Single-Center Real-World Retrospective Study

Abstract

Background: Patients with aggressive lymphomas who present with advanced disease, impaired functional status, or multiple comorbidities often require careful clinical optimization before initiating definitive chemotherapy. In this context, pre-phase therapy is used to reduce early treatment-related risk and improve tolerance of subsequent lymphoma-directed regimens. However, evidence regarding cyclophosphamide-based pre-phase therapy in adults with aggressive lymphomas remains limited, particularly in high-risk real-world populations. Objectives: This study aimed to describe clinical outcomes and documented adverse events among adults who received cyclophosphamide-based pre-phase therapy at a tertiary oncology center. Methods: We conducted a single-center retrospective cohort study at King Abdullah Medical City between January 2015 and December 2022. Adults aged 18 years or older who received cyclophosphamide-based prephase therapy before definitive lymphoma-directed treatment were included. Patient demographics, lymphoma subtype, disease stage, Eastern Cooperative Oncology Group (ECOG) performance status, treatment details, subsequent chemotherapy exposure, response, recurrence, mortality, and adverse events were extracted from the electronic medical records. Data were summarized using descriptive statistics. Results: Fifty-five patients were included. The median age was 51 years. Advanced disease was common: 38 patients (69.1%) had Ann Arbor stage IV disease, and 27 (49.1%) had an ECOG performance status of 3 - 4. Diffuse large B-cell lymphoma was the most frequent diagnosis (43.6%). Cyclophosphamide alone was the most common pre-phase regimen (78.2%), and corticosteroids were administered to 33 patients (60%). The median cyclophosphamide dose was 200 mg/m2 over 3 - 5 days. Complete response occurred in 2 patients (3.6%), partial response in 3 (5.5%), stable disease in 36 (65.5%), and progressive disease in 14 (25.5%). Thirty-one patients (56.4%) died. Among 47 patients with available 1-year follow-up, 17 (36.2%) were alive at 1 year. The most frequently documented adverse events were thrombocytopenia (45.5%), fatigue (38.2%), gastrointestinal adverse events (30.9%), and infections (30.9%). Conclusions: In this real-world cohort of clinically vulnerable patients with aggressive lymphomas, cyclophosphamide-based pre-phase therapy was used primarily in individuals with advanced-stage disease and poor performance status. Clinical responses were limited and mortality was high, which may reflect the advanced disease burden, poor performance status, and comorbidity profile of this clinically high-risk population. Tumor lysis syndrome was infrequently documented; however, the absence of a comparator group, retrospective adverse-event ascertainment, and potential confounding by disease severity and subsequent chemotherapy preclude conclusions regarding the protective effect of pre-phase therapy. Documented adverse events should be interpreted cautiously given the retrospective design, the lack of a comparator group, mixed lymphoma subtypes, variable corticosteroid use, and subsequent chemotherapy exposure. Further prospective studies are needed to define the optimal pre-phase approach for high-risk patients with aggressive lymphomas.