Aljurf, Mahmoud

Abstract Background In advanced-stage classical Hodgkin lymphoma (cHL), achieving a negative interim PET (iPET) after two cycles of ABVD is generally considered a favorable prognostic marker. Most patients with early metabolic response proceed to complete therapy without residual disease. However, a subset of patients experience discordant end-of-treatment (EOT) findings, with evidence of the disease despite an initial complete response. This study aimed to identify baseline clinical features that might help predict this unexpected outcome.Methods A retrospective review was conducted of 122 patients with stage III or IV cHL treated at our institution between 2016 and 2024. All patients achieved complete metabolic response (Deauville score ≤3) on iPET following two cycles of ABVD. Clinical and laboratory data, including IPS score, bone marrow, and extranodal involvement, were collected. The primary outcome was residual disease identified at EOT-PET. Logistic regression was used to identify predictive factors. Disease-free survival (DFS) was estimated using Kaplan-Meier analysis.Results Of the 122 patients with negative iPET scans, 21 (17.2%) were found to have residual uptake on EOT-PET. The median age was 28 years; 63% were male, and 70.5% had nodular sclerosis subtype. Most patients (69.7%) had stage IV disease. In univariate analysis, no baseline variable- including IPS score, bone marrow involvement, extranodal disease, or B symptoms- was significantly associated with residual PET positivity. However, in multivariate analysis, stage IV disease emerged as an independent predictor, with a statistically significant association with residual disease at EOT (OR 3.32; 95% CI, 0.97–11.37; p = 0.041). The median follow-up was 28.8 months. The median DFS was not reached, and the estimated two-year DFS was 83%.Conclusions While early metabolic remission on interim PET is reassuring, a notable proportion of patients still demonstrate residual disease by the end of therapy. Stage IV disease was independently associated with this outcome when adjusted for other variables. No significant associations were identified with IPS score, bone marrow, or extranodal involvement. These findings suggest that relying solely on interim PET may overlook residual risk in a subset of patients, particularly those with extensive disease burden at baseline.

ABSTRACT Transformed follicular lymphoma (tFL) is typically associated with chemotherapy resistance and a poor prognosis. There are limited data regarding outcomes after CD19‐directed chimeric antigen receptor T‐cell (CAR T) therapy in relapsed/refractory (R/R) tFL. A total of 923 adult patients with R/R tFL who received commercial CD19 CAR T therapy between 2017 and 2023 were identified in the Center for International Blood and Marrow Transplant Research registry. Median age was 64 years (range: 30–86) and median prior lines of therapy was 4 (range: 1–18). Most patients (78%) received axicabtagene ciloleucel, with 67% of patients having resistant disease at the time of CAR T infusion. At a median follow‐up of 25 months (range: 1–72) from CAR T infusion, the 2‐year overall survival (OS) was 57% (95% CI: 53–60) and progression‐free survival (PFS) was 43% (95% CI: 40–47). The 2‐year cumulative incidences of relapse or progression (rel/prog) and non‐relapse mortality (NRM) were 47% (95% CI: 44–51) and 9% (95% CI: 7–11), respectively. The overall response rate to CAR T was 76%, with a complete response rate of 63%. Grade ≥ 3 cytokine release syndrome (CRS) was observed in 7.1% and grade ≥ 3 immune effector cell–associated neurologic syndrome (ICANS) in 21.6% of patients. Multivariable analysis suggested that resistant disease status at the time of CAR T, use of bridging therapy, and high comorbidity index ≥ 3 were associated with inferior PFS and OS. Older age ≥ 60 significantly increased the risk of NRM. Our study suggests that CD19 CAR T is effective and safe for tFL.

Outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult acute lymphoblastic leukemia (ALL) have improved over time. Studies have shown that total body irradiation (TBI) is the preferable type of myeloablative conditioning (MAC). However, outcomes based on central nervous system (CNS) involvement, namely CNS-positive versus CNS-negative, have not been compared. Here, we evaluated outcomes of 547 patients (CNS-positive = 96, CNS-negative = 451) who were allografted in the first complete remission (CR1) between 2009 and 2019. Primary endpoint was leukemia-free survival (LFS). Median follow-up was not different between the CNS-positive and CNS-negative groups (79 versus 67.2 months, P = 0.58). The CNS-positive group were younger (median age 31.3 versus 39.7 years, P = 0.004) and were allografted more recently (median year 2012 versus 2010, P = 0.003). In both groups, MAC was the preferred approach (82.3% versus 85.6%, P = 0.41). On multivariate analysis, the CNS-positive group had higher incidence of relapse (RI) (hazard ratio [HR] = 1.58 [95% confidence interval (CI) = 1.06-2.35], P = 0.025), but no adverse effect on LFS (HR = 1.38 [95% CI = 0.99-1.92], P = 0.057) or overall survival (OS) (HR = 1.28 [95% CI = 0.89-1.85], P = 0.18). A subgroup multivariate analysis limited to CNS-positive patients showed that a TBI-based MAC regimen resulted in better LFS (HR = 0.43 [95% CI = 0.22-0.83], P = 0.01) and OS (HR = 0.44 [95% CI = 0.21-0.92], P = 0.03) and lower RI (HR = 0.35 [95% CI = 0.15-0.79], P = 0.01). Another subgroup analysis in CNS-negative patients showed that MAC-TBI preparative regimens also showed a lower RI without a benefit in LFS or OS. While a MAC-TBI allo-HCT regimen may not be suitable to all, particularly for older patients with comorbidities, this approach should be considered for patients who are deemed fit and able to tolerate.