Understanding Hodgkin and B-Cell Non-Hodgkin Lymphoma Progression in Patients Awaiting Autologous Transplant in a...

Wait times for autologous hematopoietic cell transplantation (auto-HCT) are often prolonged in resource-constrained countries due to logistical and social limitations. In chemosensitive lymphomas, such delays may lead to disease progression or relapse. However, data on the impact of these delays on the incidence of disease progression/relapse and associated risk factors for earlier progression/relapse on the waiting list are still limited. Our objectives were to evaluate the impact of wait times for auto-HCT on progression/relapse in chemosensitive B-cell lymphomas and identify clinical factors associated with progression and survival. We conducted an ambispective, single-center cohort study consisting of 92 patients with chemosensitive classical Hodgkin lymphoma (CHL) and 73 with chemosensitive B-cell non-Hodgkin lymphoma (B-NHL) referred for auto-HCT between 2018 and 2023. B-NHL diagnoses included diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS; N = 33), mantle cell lymphoma (MCL; N = 26), and follicular lymphoma (FL; N = 14). Cumulative incidence of progression/relapse during the waiting list was estimated using competing-risk methods. Multivariable regression models were used to identify independent predictors of progression/relapse and overall survival. Among CHL patients, 37 of 92 (40%) experienced progression/relapse while waiting, with a median time to progression/relapse of 1.8 months (IQR, 1.5 to 3.0), and a cumulative incidence of progression/relapse of 29% at 3 months. Median wait time for auto-HCT in CHL was 2.7 months (IQR, 1.91 to 3.62). In multivariate analysis, ECOG performance status >1 at diagnosis, primary refractory disease, and being in partial response at waitlist entry were independently associated with a higher risk of progression/relapse during the wait. Of the 55 CHL patients without progression/relapse, 50 (91%) were transplanted at first referral, compared to only 20 (54%) of the 37 patients with confirmed progression/relapse. Multivariate analysis indicated that for CHL patients, undergoing auto-HCT and disease status at waitlist entry were significant predictors of overall survival. Among B-NHL patients progression/relapse occurred in 34 of 73 (47%) patients while waiting. Cumulative incidences of progression/relapse at 1, 3, and 6 months were 3%, 47%, and 72% for DLBCL; 4%, 12%, and 25% for MCL; and 0%, 15%, and 25% for FL, respectively. Median wait time was 2.9 months (IQR, 2.0 to 4.8). Of 39 B-NHL patients without progression/relapse, 29 (74%) were autografted. Among 34 with progression/relapse, only 8 (24%) underwent transplant after salvage therapy; the remainder lost eligibility. In multivariate analysis, DLBCL diagnosis, older age, and primary refractoriness or early relapse were independently associated with progression/relapse. Progression/relapse was significantly associated with worse overall survival, whereas wait time and auto-HCT were not. Our findings highlight the high progression rate among B-cell lymphoma patients in an auto-HCT waiting list, especially those with diagnosis of DLBCL, underscoring the urgent need for explicit prioritization strategies in resource-limited settings. Implementing explicit triage criteria for high-risk patients may reduce waitlist progression/relapse and improve outcomes. We also propose that maximum acceptable wait times for auto-HCT in resource-limited settings should be targeted as four weeks for CHL in partial response and DLBCL NOS, and three months for CHL in complete response, MCL and FL.