The current management of retinoblastoma involves chemotherapy by the intravenous, intra-arterial, intravitreous or intra-aqueous delivery routes. These routes can adequately control solid tumour, subretinal seeds, vitreous seeds or aqueous seeds. Intravenous chemotherapy using vincristine, etoposide and carboplatin is commonly used for retinoblastoma control. According to the International Classification of Retinoblastoma, intravenous chemotherapy provides globe salvage with tumour control in 96% of Group A, 90% of Group B and Group C, 68% of Group D and 32% of Group E eyes. Intra-arterial chemotherapy, using melphalan, topotecan and/or carboplatin with delivery from the femoral artery up to the ophthalmic artery to the eye, is particularly used for unilateral retinoblastoma. This alternative has more localised ocular complications but offers more powerful tumour control. Intravitreal chemotherapy, using melphalan and topotecan, can control vitreous seeding, but most specialists employ high-dose topotecan for control of vitreous seeds and some solid tumours and even subretinal seeds. Intra-aqueous chemotherapy, using melphalan or topotecan and can be effective for aqueous seeding. There is still a role for plaque radiotherapy in non-chemotherapy-responsive tumours and enucleation for massive disease that doesn't fully respond to chemotherapy or demonstrates high-risk disease. The management of retinoblastoma has evolved to the current day with several routes of chemotherapy delivery.

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.

BACKGROUND: Chemoimmunotherapy (ChIt) has been proven to be an effective treatment for patients with refractory high-risk neuroblastoma (HR-NBL). The objective was to assess the appearance of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after high-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) in patients previously treated with ChIt for refractory HR-NBL. METHODS: Nineteen patients were treated with ChIt based on dinutuximab beta for refractory NBL and underwent ASCT. Six patients underwent HDC with ASCT according to the SIOPEN protocol (Busulfan and Melphalan (BuMel)). Treosulfan and Melphalan (TreoMel) were used in 13 patients. The occurrence of VOD/SOS was analysed. The Mann-Whitney U test was used to analyse the correlation between VOD/SOS and potential risk factors. RESULTS: VOD/SOS developed in five out of six patients when BuMel was used after ChIt (3 pts, grade 4; 2 pts, grade 3), resulting in two deaths. No VOD/SOS was observed in patients receiving TreoMel. Other analysed factors had no influence of VOD/SOS occurrence and the only identified risk factor was BuMel administered after ChIt. CONCLUSIONS: Patients with refractory HR-NBL treated with ChIt and DB did not present life-threatening toxicities or severe liver toxicities during the ChIt cycles and continued to HDC with ASCT according to SIOPEN guidelines. The incidence of severe VOD/SOS after ChIt and subsequent BuMel was higher than expected, with severe course resulting in two deaths. Taking into account the possible increase in the risk of VOD/SOS after BuMel used after chemotherapy combined with DB, careful observation with early VOD/SOS treatment in patients after ChIt is recommended and TreoMel regimen may be considered as less toxic.

Mechanisms of systemic administration of cytotoxic and immunomodulatory agents are hindered due to poor intratumoral retention and off-target toxicities. While Antibody-Drug Conjugates (ADCs) have achieved substantial clinical success and validated the paradigm of targeted therapy, their large size (∼150 kDa) limits their ability to cross blood vessels and interstitial spaces, especially in the dense, collagen-rich stroma of aggressive solid tumors. As a smaller alternative for drug delivery, Tumor-Homing Peptides (THPs) allow for improved tissue permeability, low immunogenicity and rapid systemic clearance. Here, we examine THPs discovery and development trajectory, from phage display strategies to current deep learning-driven design methodologies. We analyze the structural and functional biology of the predominant internalization pathways like the Neuropilin-1 (NRP-1) dependent C-end Rule (CendR) and the Sortilin (SORT1) scavenger receptor, and their use to promote deep tissue penetration. Finally, we assess the translational landscape of early 2026, including the recent FDA withdrawal of the lipophilic peptide-conjugated melphalan flufenamide (Pepaxto®) and the recent clinical success of the cyclic peptide certepetide for pancreatic adenocarcinoma and the ongoing promising studies with chemically constrained bicyclic peptides.

Isolated limb perfusion (ILP) represents a regional oncological therapeutic approach, predominantly applied in the management of locally advanced soft tissue sarcomas of the extremities and malignant melanomas. The technique involves temporary vascular isolation of the affected limb from the systemic circulation, followed by perfusion under strictly controlled hyperthermic conditions using a cytotoxic agent combination, most commonly melphalan in conjunction with human recombinant tumor necrosis factor-alpha. The primary objective of ILP is to achieve high locoregional drug concentrations while limiting systemic exposure, thereby promoting substantial tumor regression and enabling limb preservation. The most commonly reported procedure-related complications include regional and systemic perfusion reactions and postoperative compartment syndrome. When performed in high-volume specialized centers, ILP is regarded as a safe and efficacious treatment modality, with limb preservation rates of up to 93% reported in soft tissue sarcomas.

Sporadic late-onset nemaline myopathy (SLONM) is a rare, acquired myopathy often associated with monoclonal gammopathy. We report a 48-year-old man presenting with progressive proximal and truncal muscle weakness in whom SLONM associated with smoldering myeloma was highly suspected. He received daratumumab, lenalidomide, and dexamethasone followed by high-dose melphalan with autologous stem cell transplantation and posttransplant therapy. Treatment resulted in marked improvement in muscle strength and performance status. The patient achieved minimal residual disease negativity and has remained relapse-free for 5 years. This case highlights the potential efficacy of daratumumab-based therapy followed by transplantation in SLONM associated with plasma cell dyscrasia. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome (CBMFS) primarily managed with corticosteroids and blood transfusions; however, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the sole curative option when these therapies fail or relapse occurs. We report the case of a 21-year-old woman diagnosed with DBA caused by an RPS19 mutation shortly after birth. Although she responded well to corticosteroid therapy until 18 years of age, discontinuation led to relapse and subsequent transfusion dependence, necessitating allogeneic transplantation. In the absence of a human leukocyte antigen (HLA)-matched donor, she underwent post-transplantation cyclophosphamide (PT-Cy)-based haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) at 21 years of age, utilizing her father as the donor. Myeloablative conditioning was performed using fludarabine, melphalan, and busulfan. For acute graft-versus-host disease (GVHD) prophylaxis, PT-Cy (50 mg/kg on days 3 and 4), tacrolimus, and mycophenolate mofetil were administered, resulting in successful neutrophil engraftment on day 16 post-transplantation. Although the patient developed acute GVHD (grade II), it resolved with corticosteroid therapy. Post-discharge, she was readmitted due to acute gastrointestinal GVHD (grade II), which improved after methylprednisolone administration. She was discharged on day 92 and achieved complete transfusion independence for the past 5 years, making this the first reported case of long-term survival following PT-Cy-based haplo-PBSCT for this condition. Including our patient, there are only four reported cases of allo-HSCT using PT-Cy for adult patients with DBA; notably, all patients survived without developing severe GVHD or infectious complications. Generally, transplant outcomes for DBA worsen with increasing age due to severe GVHD and organ damage secondary to long-term iron overload. Given that DBA is a non-malignant disease, meticulous attention must be paid to prevent unnecessary GVHD and graft failure. In adult patients with DBA, PT-Cy yielded successful engraftment and safety, with no incidence of severe GVHD, leading to long-term survival and minimal complications. These findings suggest that allo-HSCT utilizing PT-Cy remarkably expands donor options for congenital bone marrow failure syndromes. Consequently, this approach is expected to become a promising therapeutic strategy not only for hematologic malignancies but also for non-malignant disorders.