BEAM (carmustine, etoposide, cytarabine, and melphalan) remains the most used chemotherapy for autologous hematopoietic stem cell transplantation (HSCT) in chemosensitive relapsed Hodgkin's lymphoma (HL). Nevertheless, alternatives have been developed to overcome drugs availability, costs, or potential toxicities. These include BeEAM (substitute carmustine with bendamustine), FEAM (using fotemustine instead of carmustine), TEAM (incorporating thiotepa instead of carmustine) and EAM (without bendamustine, fotemustine, thiotepa or carmustine). We analysed 13207 adults with HL who underwent HSCT in EBMT centers from 2010 to 2022. Chemotherapy was BEAM in 77% (n = 10167), FEAM in 13% (n = 1702), BeEAM in 6% (n = 729), TEAM in 3% (n = 365), and EAM in 2% (n = 244). In multivariable analysis, BeEAM was associated with decreased overall survival (OS) (HR 1.61, p = 0.003) and progression free survival (PFS) (HR 1.48, p < 0.001), higher relapse incidence (RI) (HR 1.43, p < 0.001) and non-relapse mortality (NRM) (HR 1.85, p = 0.04). EAM regimen was also associated with decreased OS (HR 1.55, p = 0.019). Propensity score matching was performed as a sensitivity analysis and confirmed the results of the multivariable analysis. We observed poorer outcomes in patients who received bendamustine in our cohort.

Leptomeningeal and ependymal seeding (LES) is an uncommon but devastating complication of high-grade gliomas, and its incidence appears to be rising as improved multimodal treatment prolongs patient survival. Intraoperative ventricular entry and repeated surgery are well-established risk factors, and their coexistence with carmustine wafer implantation raises technical and diagnostic questions that remain underexplored in the literature. We report the case of a 37-year-old man with a right parieto-occipital WHO grade III anaplastic astrocytoma, initially treated with gross total resection and standard chemoradiotherapy. Following local recurrence at 19 months and a second resection with cranioplasty, the patient developed advanced tumor progression 17 months later that required a third surgery, during which an incidental opening of the lateral ventricle occurred; the defect was sealed with Gelfoam (Pfizer Inc., New York, United States) and Surgicel (Ethicon, Inc., Raritan, New Jersey, United States), and eight carmustine wafers were subsequently implanted in the surgical bed. Definitive histopathology documented malignant transformation to glioblastoma (WHO grade IV) with mutant IDH1. Two months later, the patient developed acute neurological deterioration with diffuse ependymal and leptomeningeal enhancement; because lumbar puncture was relatively contraindicated, magnetic resonance spectroscopy (MRS) directed at the hypothalamic and cervical regions of abnormal enhancement showed a pattern highly suggestive of active neoplastic seeding (choline/N-acetylaspartate (Cho/NAA) 8.0, choline/creatine (Cho/Cr) 3.2). Despite high-dose corticosteroid therapy, the patient died of progressive motor and respiratory decline. This case illustrates the diagnostic dilemma that arises when intraoperative ventricular entry and subsequent carmustine wafer implantation coincide in the same procedure: distinguishing true leptomeningeal tumor seeding from carmustine-induced chemical leptomeningitis, since both can produce an indistinguishable enhancement pattern on conventional MRI. We also discuss the clinical rationale for using carmustine wafers as a local therapeutic bridge. At the same time, a patient awaits formal oncologic evaluation, a wait that is often prolonged in publicly funded health systems. We review the reported evidence on risk factors for cerebrospinal fluid (CSF) dissemination, carmustine-related complications near the ventricular system, the role of MRS when lumbar puncture is contraindicated, and the relevance of the 2021 WHO nomenclature for interpreting this case.

Glioblastoma multiforme remains one of the most aggressive and lethal central nervous system malignancies, primarily due to the restrictive nature of the blood-brain barrier which severely limits the efficacy of systemically administered chemotherapeutics. To address this critical challenge, this study aims to overcome the limitations of conventional glioblastoma treatment by developing solid lipid nanoparticles (SLNs) co-loaded with temozolomide and carmustine for targeted intranasal administration. The developed SLNs were synthesized and comprehensively evaluated for biodistribution and pharmacokinetics in mice following nose-to-brain delivery. Drug concentrations in the brain and peripheral tissues were quantified using a robust and validated HPLC method. Therapeutic efficacy was further investigated in an in vivo glioblastoma model established by intracerebral U87MG cell implantation. Tumor progression was monitored via precise volume measurements and survival analysis, while the safety profile was assessed through comprehensive acute and subacute toxicity studies. Pharmacokinetic analysis confirmed effective brain tissue distribution and sustained drug levels. Furthermore, the dual-loaded SLN treatment demonstrated a significant reduction in tumor volume and remarkably extended survival rates compared to the control and conventional treatment groups. Ex vivo pathological evaluations and systemic toxicity studies indicated no mortality or gross organic damage at the tested doses, suggesting an acceptable systemic safety profile under the evaluated conditions. However, further rigorous evaluations regarding local nasal mucosal toxicity and long-term renal accumulation are required to fully establish the safety limits of this carrier system. Overall, intranasally administered SLNs provide a promising nanoparticle-based strategy that offers a viable, low-toxicity alternative to improve clinical outcomes in aggressive brain tumors.

Nitrosoureas are cytotoxic chemotherapeutic drugs that cause cell death by DNA damage. They are used to treat malignancies, including malignant glioblastomas, Hodgkin's and non-Hodgkin lymphomas, and pancreatic islet cell tumors. Three of the most commonly used nitrosourea compounds are carmustine (BCNU), lomustine (CCNU), and fotemustine. Nitrosoureas are lipophilic chemicals with antitumor and cytotoxic effects via alkylating and carbamoylating compounds; they are active in multiple cell cycle phases. Lomustine readily crosses the blood-brain barrier and is commonly used for recurrent glioblastoma multiforme; in some European countries, fotemustine is used instead of lomustine. Carmustine was the first nitrosourea developed for public use (United States Food and Drug Administration approval in 1977). The drug has been widely discontinued due to toxicity, intravenous (IV) administration, and low availability.. Nitrosoureas are used alongside other chemotherapeutic agents (such as procarbazine, lomustine, and vincristine, a first-line regimen for oligodendroglioma) or as stand-alone chemotherapy agents. Streptozocin has methylnitrosourea activity against pancreatic islet cell tumors. Nitrosoureas are associated with significant and severe adverse effects, including leukoencephalopathy, pulmonary toxicity, nephrotoxicity, hepatotoxicity, neurotoxicity, myelosuppression, secondary leukemias, nausea, vomiting, stomatitis, alopecia, anemia, anorexia, and phlebitis and burning at the injection site. Due to their severe side effect profiles, nitrosoureas are mostly used for tumor recurrence or refractory cases. Nitrosourea metabolites are primarily excreted through the kidneys. 

Reticulocalbin-1 (RCN1), an endoplasmic reticulum (ER)-related gene, demonstrates critical regulatory functions in cellular growth. RCN1 has been previously revealed to be closely associated with initiation, metastasis and chemosensitivity in some tumors. However, the prognostic significance of RCN1 and its influence on the cancer immune microenvironment remains unclear. By leveraging multi-omics data from TCGA and GEO, this study delineated the expression profile of RCN1 across various human malignancies and normal tissues. Analysis of RCN1 expression in correlation with tumor immune microenvironment characteristics was performed using CIBERSORT and ssGSEA. Pan-cancer prognostic value was assessed via multiple survival models. In glioma, immunohistochemistry, co-culture, and qPCR were utilized to further investigate the role of RCN1 in tumor immunity and prognosis. Drug-specific responses to RCN1 expression were probed for cisplatin, irinotecan, carmustine and lomustine, which are the common chemotherapeutic agents used in glioma clinical treatment. The results indicate that RCN1 is a key gene with the potential to promote the progression of multiple tumors and is closely associated with tumor immune response, particularly macrophage activation. In glioma, overexpression of RCN1 promotes tumor proliferation and indicates poor prognosis, and is closely related to endoplasmic reticulum stress. Knockdown of RCN1 enhances the chemotherapeutic efficacy of carmustine and lomustine. In conclusion, our research positioned RCN1 as an important oncogene from a pan-cancer perspective and validated its role in glioma. In particular, RCN1 is closely associated with the immune microenvironment and endoplasmic reticulum stress during tumorigenesis. In addition, RCN1 has broad prospects in guiding tumor chemotherapy pending physiological in vivo validation.

The BEAM regimen (carmustine, etoposide, cytarabine, melphalan) is the standard conditioning regimen for autologous hematopoietic stem cell transplantation (auto-HSCT) in diffuse large B-cell lymphoma (DLBCL). Due to global carmustine shortages, bendamustine-based BeEAM has been proposed as an alternative. This study compared clinical outcomes between BEAM and BeEAM regimens in DLBCL patients undergoing auto-HSCT. A retrospective analysis of 60 consecutive DLBCL patients undergoing auto-HSCT (2019-2024) was conducted. Patients received either BEAM (n=45) or BeEAM (n=15) conditioning. Endpoints included progression-free survival (PFS), overall survival (OS), and treatment response. Survival outcomes were analyzed using the Kaplan-Meier method and the log-rank test. The BEAM group demonstrated significantly superior 3-year PFS (88.7% vs. 75.8%, p=0.024) and OS (95.3% vs. 68.9%, p=0.017) compared to BeEAM. In consolidation patients (n=50), BEAM showed numerically better PFS (89.5% vs. 81.8%, p=0.25) and OS (94.5% vs. 80.8%, p=0.069). Among patients with a pre-transplant complete response (n=52), BEAM showed significantly improved 3-year OS (94.2% vs. 68.9%, p=0.04) and numerically better PFS (86.1% vs. 75.8%, p=0.059). All patients engrafted successfully with comparable neutrophil and platelet recovery. The complete response rate improved from 86.7% (52/60) pre-transplant to 100% (60/60) post-transplant. In summary, BEAM may be associated with better outcomes than BeEAM in this cohort. However, due to the limited sample size, these findings should be interpreted as exploratory, and larger prospective studies are needed to validate these observations.

Redox homeostasis is driven by the ratio of the concentrations of cellular redox couples. The aim of this study was to reduce 2GSH/GSSG turnover in an ex vivo ileum by the irreversible inhibition of glutathione reductase (GR) activity (by BCNU) and evaluate its effects on contractility, antioxidant enzyme activity, and thiol levels. Increasing concentrations of BCNU as well as a single EC50 BCNU dose significantly reduced both contraction amplitude and GR activity. The addition of cumulative doses of both GSH and GSSG after EC50 BCNU caused further dose-dependent amplitude reduction, but turned GR activity to control levels and reduced CuZn-superoxide dismutase activity; cumulative doses of GSH also decreased catalase activity. Both GSH and GSSG cumulative doses decreased the contractility of non-treated control ileum in a dose-dependent manner, while GSH also increased glutathione peroxidase (GPx) activity. The correlation analysis showed a negative relationship between contractility and non-protein thiols, and positive correlations between catalase and GPx activities in BCNU treated ileum, as well as between GPx and non-protein thiols in solvent controls. The results present a framework for how glutathione turnover and ileum contractility are linked.

Consolidation therapy for primary CNS lymphoma (PCNSL) includes high-dose chemotherapy with autologous stem-cell transplantation (HCT-ASCT), yet its efficacy compared with non-myeloablative chemoimmunotherapy remains uncertain. This study aimed to provide randomised comparative evidence on the efficacy and safety of thiotepa-based HCT-ASCT versus non-myeloablative R-DeVIC consolidation after uniform MATRix induction in newly diagnosed PCNSL.

Acute appendicitis is an exceptionally rare complication of autologous hematopoietic stem cell transplantation (HSCT) and represents a diagnostic challenge, since its presentation overlaps with conditioning-related gastrointestinal toxicity and neutropenic enterocolitis. Published data are limited to isolated case reports, and its occurrence during autologous stem cell transplantation (ASCT) for human immunodeficiency virus (HIV)-associated lymphoma has not previously been described. We report the case of a 39-year-old man with HIV-associated diffuse large B-cell lymphoma (DLBCL), non-germinal center subtype, Ann Arbor stage IV with gastric involvement, and a high-risk age-adjusted International Prognostic Index (score three). After failure of first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with a Deauville score of four on interim positron emission tomography-computed tomography, complete metabolic remission was achieved with two cycles of second-line rituximab, dexamethasone, cytarabine, and carboplatin (R-DHAC). The patient then proceeded to carmustine, etoposide, cytarabine, and melphalan (BEAM)-conditioned ASCT under controlled HIV viral load and persistent CD4 lymphopenia. On the day of stem cell infusion (day zero), he developed right lower quadrant tenderness associated with elevated inflammatory markers; abdominopelvic computed tomography demonstrated acute appendicitis. Emergency laparoscopic appendectomy revealed ulcerative appendicitis without tumor infiltration on histopathology. The postoperative course during aplasia was complicated by septic shock due to multidrug-resistant Pseudomonas aeruginosa bacteremia, with a favorable evolution to broad-spectrum antibiotic therapy and vasopressor support. Neutrophil engraftment occurred on day +14, and the patient was discharged on day +20, with no further complications and a complete remission maintained at six months of follow-up. This case illustrates that acute appendicitis may occur as early as the day of stem cell infusion. Its presentation may be initially indistinguishable from melphalan-induced gastrointestinal toxicity, which makes early abdominopelvic CT indispensable for an early diagnosis. It also shows that, even when surgical source control is timely, profound aplasia and the HIV-related CD4 lymphopenia predispose to severe infectious complications. This justifies anticipatory broad-spectrum coverage adapted to local multidrug-resistant epidemiology and close multidisciplinary monitoring throughout the aplastic phase.

In this study, density functional theory (DFT) calculations and molecular dynamics (MD) simulations were combined to investigate the interaction mechanism and drug-loading performance of chitosan (CS) as a carrier for carmustine (BCNU). DFT results indicate that adsorption of BCNU onto the CS surface is an exothermic process, with adsorption energies ranging from -8.69 to -26.41 kcal·mol[-1]. The complexes are primarily stabilized by hydrogen bonding and van der Waals (vdW) interactions. Among them, complex D exhibits the most negative adsorption energy and the greatest structural stability. FMO analyses show that the HOMO is mainly localized on CS, whereas the LUMO is localized on BCNU. The complexes exhibit a smaller Eg than isolated BCNU and show enhanced electrophilicity relative to isolated CS, which is beneficial for the chemical reactivity of the drug. QTAIM and NCI analyses confirm that medium strength hydrogen bonds and vdW forces dominate the non-covalent interactions between CS and BCNU. MD simulations reveal the assembly behavior and stability of the complexes at different drug loading ratios. Among the studied systems, the 8BCNU@8CS complex with a drug loading of 14.08 wt% exhibits the lowest mean square displacement and solvent accessible surface area, suggesting a more compact and stable encapsulation structure, which may be conducive to achieving sustained release based on simulation conditions. This work elucidates the atomic-scale interaction mechanisms between CS and BCNU and provides a theoretical basis for designing efficient, stable CS-based nanocarriers for BCNU delivery.

The European Group for Blood and Bone Marrow transplantation Practice Harmonization and Guidelines Committee together with the Lymphoma Working Party convened 23 experts in Hodgkin lymphoma, transplantation, and radiation oncology, to develop consensus recommendations on the use of autologous and allogeneic haematopoietic cell transplantation (HCT) in relapsed or refractory Hodgkin lymphoma. Through a structured literature review and a 2-day workshop in Berlin, Germany, on Sept 29 and 30, 2025, the panel established guidance across major clinical decision points. The outcome of this review and workshop include the following recommendations. Salvage therapy should include brentuximab vedotin or checkpoint inhibitors, or both, with metabolic complete response preferred before autologous HCT. BEAM (carmustine, etoposide, cytarabine and melphalan) remains the most commonly used conditioning regimen, and autologous HCT continues to be the standard for chemosensitive relapse. Peri-transplantation radiotherapy could be considered for PET-positive or residual disease. Brentuximab vedotin consolidation is recommended for patients at high-risk. Allogeneic HCT is advised for eligible patients who relapse after autologous HCT, ideally with reduced intensity conditioning and post-transplantation cyclophosphamide as graft-versus-host disease prophylaxis. Routine maintenance after allogeneic HCT is not recommended; relapse management should be tailored and can involve donor lymphocyte infusion, brentuximab vedotin, checkpoint inhibitors, chemotherapy, radiotherapy, or clinical trial enrolment.

Purpose The aim of this retrospective single-center study was to evaluate the safety and efficacy of palliative intra-arterial chemoperfusion (IAC) for patients diagnosed with recurrent or post-therapeutic progressive symptomatic lung cancer brain metastases (LCBM). Materials and methods A total of 10 patients (five women and five men; median age: 56 years (range: 40-80 years)) with recurrent or post-therapeutic LCBM were included. Chemotherapy consisted of either carmustine or a combination of mitomycin C, gemcitabine, and cisplatin. The radiological follow-up was performed using magnetic resonance imaging (MRI) according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The overall survival (OS) was calculated using the Kaplan-Meier method. Results All patients were treated with prior systemic therapy, and seven patients additionally received radiation therapy. A total of 37 sessions of IAC (3.7/patient) were performed. No major complications occurred. The mean sum of the longest diameter (SLD) was 4.5±1.2 cm for all patients prior to treatment. The mean SLD for patients with radiological follow-up was 3.9±2.1 cm after treatment. Four patients (4/8) developed progressive disease. Three patients (3/8) achieved stable disease, and one patient (1/8) showed complete response. None of the patients had partial response. Two patients (2/10) were not assessable due to loss of radiological imaging post-interventional. The mean OS time was 9.7 months (95% CI: 2.4-17.0). Conclusion Although IAC seems to be a safe approach for palliative patients with recurrent or post-therapeutic progressive symptomatic LCBM, further studies with a larger patient population are needed to confirm its efficacy.