This prospective phase 2 multicentre non-randomised parallel arm study of haploidentical peripheral blood stem cell (PBSC) transplantation with post-transplant cyclophosphamide (PTCy) recruited 77 patients: 50 received reduced-intensity conditioning (RIC) with PTCy post stem cell infusion while 27 underwent myeloablative conditioning (MAC) with PTCy given after lymphocyte but prior to infusion of CD34 selected stem cells. The primary end-point 1-year overall survival (OS) was 86% for RIC and 78% for MAC, meeting the pre-specified targets for efficacy. At 4 years, OS was 63% for RIC and 60% for MAC with low non-relapse mortality of RIC 18% and MAC 4%. Engraftment was faster in the MAC arm (median time to neutrophil and platelet engraftment 11 and 15 days; 21 and 24 days in the RIC arm). The economic analysis showed that MAC had higher initial transplant costs, RIC incurred greater post-transplant monitoring costs, resulting in higher overall costs (RIC £156 711, MAC £131 092). Quality of life (QoL) outcomes in both indicated significant post-transplant declines at 3 months but returned to baseline by 12 months. This study confirms the long-term safety of using PBSC with PTCy in haploidentical transplants, with a good quality of life and reasonable costs.
Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS) and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes following thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) delivered at relapse were compared following propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). 2-year PFS estimates were 40.4%, 43.9% and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: HR=0.57; P=0.005; and OS: HR=0.62; P=0.023) and CNS-isolated relapses (PFS: HR=0.55; P=0.002; and OS: HR=0.39; P<.0001) in 6-month multivariable landmark analysis. ASCT (thiotepa or non-thiotepa) also associated with improved survival in synchronous relapses (PFS: HR=0.57; P=0.023; and OS: HR=0.48; P=0.019). Higher survival with thiotepa-ASCT compared to CAR-T was observed in survival analyses following PSM (PFS: HR=0.45; P=0.005 and OS: HR=0.41; P=0.014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.
Abstract Psoriasis exhibits circadian rhythmicity, and chronotherapeutic benefits have been described for topical treatments. Circadian disruption, seen in shift work or time zone travel, may influence inflammatory pathways and treatment outcomes; however, the impact of circadian factors on phototherapy response remains largely unexplored. We postulated that alignment between chronotype and treatment timing, recent time zone travel and night-shift work might influence clinical response to ultraviolet B (UVB) phototherapy in psoriasis. We analysed 174 patients with psoriasis treated with UVB phototherapy between January and December 2025. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were recorded at baseline and end of treatment. Circadian-related variables were collected using questionnaires, including self-rated chronotype (morning, evening or intermediate), treatment time, recent time zone travel and night-shift work. Chronotype alignment was defined as concordance between chronotype and treatment timing (morning types treated early, evening types treated later). Patients had moderate baseline disease (median PASI 12.6). Most completed ≥ 24 UVB sessions (n = 116). Night-shift (n = 19) and non-night-shift workers (n = 155) had identical baseline median PASI (12.6). Night-shift workers showed greater numerical PASI reductions (−14.6 vs. −9.6), while DLQI (median 12) improvements were similar (−8.6 vs. −8.7). Rates of PASI 50 (≥ 50% improvement from baseline) (92.3% vs. 86.4%) and PASI 75 (69.2% vs. 54.9%) were high in both groups. Treatment timing (early: 07.00 h to 09.59 h, n = 73; late morning: 10.00 h to 11.59 h, n = 48; early afternoon: 12.00 h to 14.40 h, n = 53) did not meaningfully influence response. PASI and DLQI improvements were similar in chronotype-aligned (n = 96) and misaligned patients (n = 78) (PASI reduction −9.7 vs. −10.9; DLQI −8.5 in both), with comparable PASI 50 and PASI 75 rates. Patients with recent time zone travel (n = 53) had similar PASI improvement to nontravellers (n = 121) (−10.3 vs. −10.2). Phototherapy response was not significantly influenced by chronotype alignment, treatment timing or time zone travel. Although night-shift workers showed greater PASI improvement, small subgroup sizes and missing data limit interpretation. These findings suggest circadian factors may not impact short-term phototherapy response, but further prospective studies are warranted.
