Introduction: Nowadays, more than 80% of newly diagnosed classical Hodgkin lymphoma (HL) patients can be cured and become long-term survivors due to risk and response-adapted treatment strategies. A well-known side effect is cognitive dysfunction that appears in HL patients after chemotherapy. In the present study, we aimed to measure cognitive dysfunction in our HL patients in this study and to find potential correlations between patient-related factors, the signs and symptoms of their diseases, or therapeutic factors. Methods: We carried out a computer-assisted assessment (CANTAB) of cognitive dysfunction in 118 patients. We examined the domains of visual memory, attention, working memory, and planning. Results: The median age of 64 females and 54 males at diagnosis was 29 (13–74) and 41 (21–81) years at the completion of CANTAB. Fifty-two percent of all patients showed cognitive impairment. Attention was impaired in 35% of patients, the working memory and planning were impaired in 25%, while visual memory was affected in 22%. All the three functions showed a significant association with inactive employments status. A close correlation was found between visual memory/working memory and planning, higher age at HL diagnosis or the completion of CANTAB test, and disability pensioner status. Discussion: Our investigation suggests that patients with inactive employment status and older age require enhanced attention. Their cognitive function and quality of life can be improved if they return to work or, if it is not possible, they receive a cognitive training.

Up to 30% of patients with classical Hodgkin lymphoma (cHL) are not responsive to frontline therapy or relapse after primary treatment. In these cases, autologous hematopoietic stem cell transplantation (AHSCT) is the standard of care. The combination of brentuximab vedotin and bendamustine (BV + B) is an effective salvage regimen in this challenging subpopulation. This nationwide multicenter study investigated the real-world efficacy and safety of the BV + B regimen as a bridge to AHSCT in patients with primary refractory or relapsed cHL. A total of 41 cHL patients underwent AHSCT after receiving at least 1 cycle of BV + B (with brentuximab vedotin given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m² on days 1–2 every 4 weeks). After a median of 3 (1–6) cycles of BV + B, the objective response rate was 78%, with 29 (70.7%) patients achieving complete remission. Twelve (29.3%) patients relapsed after AHSCT, 2 (4.9%) of them died, while 2 (4.9%) patients are lost to follow-up. After a median of 17 months of follow-up, the estimated 2-year overall- and progression-free survival after AHSCT was 93 and 62%, respectively. Features of advanced disease at recurrence (p = 0.038) and the presence of stage IV cHL at relapse (p = 0.024) are strong predictor markers of unfavorable outcomes. Twenty-four (58.5%) patients experienced adverse events of any grade, while no grade IV toxicities were reported. BV + B is an effective salvage option with a manageable toxicity profile in cHL. The real-world safety and efficacy of this combination are similar to the observations made on the study population.

Autologous stem cell transplantation (ASCT) is the standard treatment of primary refractory or relapsed Hodgkin-lymphoma, which can provide a cure rate of about 50%. The aim of our study was to analyze the data of 126 HL patients undergoing AHSCT in Hungary between 01/01/2016 and 31/12/2020. We assessed the progression-free and overall survival, the prognostic role of PET/CT performed before transplantation and effect of brentuximab vedotin (BV) treatment on survival outcomes. The median follow-up time from AHSCT was 39 (1–76) months. The 5-year OS comparing PET- and PET + patients was 90% v. 74% (p = 0.039), and 5-year PFS was 74% v. 40% (p = 0.001). There was no difference in either OS or PFS compared to those who did not receive BV before AHSCT. We compared BV treatments based on their indication (BV only after AHSCT as maintenance therapy, BV before and after AHSCT as maintenance treatment, BV only before AHSCT, no BV treatment). There was statistically significant difference in the 5-year PFS based on the inication of BV therapy. Recovery rates of our R/R HL patient population, who underwent AHSCT, improved significantly. Our positive results can be attributed to the PET/CT directed, response-adapted treatment approach, and the widespread use of BV.

Már a 2000-es évek elejétől jelentősen javult a Hodgkin-lymphomás betegek teljes és betegségmentes túlélése, köszönhetően az ABVD- (adriamicin, bleomicin, vinblasztin, dakarbazin) polikemoterápia elterjedésének és a modern sugárkezelésnek. Az utóbbi években további diagnosztikus és terápiás változásoknak lehettünk tanúi, melyek a betegek túlélését tovább javítják. A legutóbbi évtizedben észlelt javulásban jelentős szerepe van a diagnosztikai fejlődésnek, így a ma már rutinszerűen, a kezelés során ismételten alkalmazott ¹⁸FDG-PET/CT vizsgálatnak, az ezen alapuló válaszadaptált kezelés(ek)nek. Az ABVD-kezelés uralkodó szerepe az első vonalbeli terápiában még mindig egyértelmű, de nagyobb rizikójú betegeknél már célzott kezelésként az anti-CD30 monoklonális antitest (a brentuximab-vedotin) és az AVD (adriamicin, vinblasztin, dakarbazin) kombinációja is elérhető. A nagy rizikójú, relabáló/refrakter betegek meggyógyításában az autológ haemopoeticus őssejtek transzplantációjának szerepe változatlanul egyértelmű, az ezt megelőző ’salvage’ kezelésekben viszont már helye lehet/van az új, célzott innovatív szereknek (brentuximab-vedotin, pembrolizumab) is. Az új terápiás lehetőségek új mellékhatásokkal is járnak, amire e betegek ellátása során fel kell készülni. Összefoglalónkban ezen új diagnosztikus és terápiás megközelítéseket mutatjuk be, saját gyakorlatunk és tapasztalataink alapján. Orv Hetil. 2023; 164(11): 403–410.

Background: Mutation of the TP53 gene is one of the major drivers of myelodysplastic neoplasias (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MR). TP53 mutations present in these hematopoietic malignancies form a distinct molecular genetic cluster with a worse prognosis than without the alteration. However, besides well-characterized hot-spot variants, a significant proportion of TP53 alterations are of uncertain clinical significance. Methods: To enlighten so far unknown aspects, bone-marrow samples from altogether 77 patients are analyzed retrospectively with the diagnosis of AML-MR (26 cases), MDS-IB (12 cases), and MDS-LB (39 cases) according to WHO 2022 guidelines. Next-generation sequencing results are correlated with histological, cytogenetic, and survival data. Results: Twenty out of the 30 TP53 mutation types detected by NGS are not categorized in current public databases; thus, their clinical significance remained mysterious. Because of the interpretation difficulties and the absence of clinical correlations, pathogenicity is established based on in silico approaches. The 12 pathogenicity classification systems, as well as protein stability, protein–DNA, protein–protein interaction, and post-translational modification analyses are applied. We found statistically significant differences between AML/MDS groups considering p53 pathogenicity, protein structural changes, and overall survival. The largest number of abnormalities with the most severe consequences are found in AML-MR cases. Conclusions: These molecular and in silico protein data further support that MDS with increased-blast (MDS-IB) is an intermediate group between AML-MR and MDS with low-blast (MDS-LB) patients, which frequently progresses to AML and is therefore considered a pre-leukemic condition.