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.

Autologous stem cell transplantation (ASCT) remains a cornerstone in the management of plasma cell dyscrasias, particularly in younger patients, despite advancements in novel therapeutic agents. However, real-world outcomes in resource-limited settings like India remain underreported. We conducted a single-center, retrospective analysis of 67 patients with plasma cell dyscrasias who underwent ASCT between December 2012 and October 2024 at a tertiary care center in Northern India. Clinical characteristics, induction regimens, transplantation details, and outcomes were evaluated. Relapse-free survival (RFS) and overall survival (OS) were calculated using Kaplan-Meier analysis, and risk factors for relapse were identified through logistic regression. The median patient age was 50 years, with a male predominance (73.1%). Multiple myeloma accounted for 88.1% of cases. Induction regimens varied, with CyBorDex being most common. Median time to neutrophil and platelet engraftment was 10 and 12 days, respectively. Febrile neutropenia occurred in 68.9% of patients, and 30-day transplant-related mortality was 7.5%. At a median follow-up of 4 years, the 5-year OS and RFS were 74.5% and 53%, respectively. High-risk cytogenetics and positive day 100 PET-CT showed trend towards higher risk of relapse. ASCT remains effective in improving survival and deepening response in plasma cell dyscrasias, even in resource-constrained settings. Relapse rates and transplant-related mortality are higher than Western cohorts, underscoring the need for improved supportive care and broader access to maintenance therapies in India.

Rheumatoid arthritis (RA) and multiple myeloma (MM) are rare coexisting conditions that present diagnostic and therapeutic challenges, and while autologous hematopoietic stem cell transplantation (auto-HSCT) is standard for MM, its effect on concomitant RA remains unclear. We report a 50-year-old woman with a 10-year history of RA who developed IgG-κ MM and underwent auto-HSCT following VRD induction and high-dose melphalan conditioning. Serial assessments showed that MM response deepened from partial remission to very good partial remission, with M protein declining and the free light chain ratio normalizing, while RA activity markedly improved-rheumatoid factor decreased from 67.8 to 5.5 IU/mL and DAS28-ESR dropped from 4.33 to 2.25, with complete resolution of joint symptoms and no severe transplant-related complications. A review of the relevant literature supports these findings, suggesting that auto-HSCT may be a safe and effective strategy for simultaneously managing both diseases, although long-term follow-up is necessary to confirm the durability of remission.

Objective: To investigate the safety and efficacy of oral melphalan as a conditioning regimen for patients with multiple myeloma (MM) who underwent autologous hematopoietic stem cell transplantation (auto-HSCT) . Methods: This retrospective cohort study collected clinical data of patients with MM who underwent auto-HSCT at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2022 to October 2023. Patients were divided into oral and intravenous groups according to the administration route of melphalan. Engraftment time (ET), overall responses, long-term outcomes, and melphalan-associated toxicities were assessed. The pharmacokinetics of melphalan were detected using a mass spectrometer. Results: This study included 48 patients with MM who met the inclusion and exclusion criteria. Of these patients, 12 received tablet melphalan and 36 had the injection formulation. Upon engraft infusion, time to the lowest level (TTLL) and ET of neutrophils in the oral group were significantly longer than those in the injection group[TTLL: median, 9.0 (7.0-13.0) d vs 7.0 (5.0-12.0) d, P<0.001; ET: median, 12.0 (10.0-14.0) d vs 11.0 (9.0-12.0) d, P<0.001]. Such a lag also happened to the TTLL and ET of platelets in the oral group compared with the injection group[TTLL: median 10.0 (9.0-15.0) d vs 9.0 (6.0-13.0) d, P=0.004; ET: median, 14.5 (11.0-17.0) d vs 12.0 (9.0-19.0) d, P=0.002]. The lowest level of neutrophils in the oral group was higher than that in the injection group (0.11×10(9)/L vs 0.02×10(9)/L, P<0.001), whereas the lowest level of platelets in both groups had no statistical difference (P>0.05). The median duration of neutropenia (<0.5×10(9)/L) was comparable between the two groups. Regarding non-hematological side effects, patients who took melphalan orally had a remarkably lower frequency of gastrointestinal toxicities as opposed to those given intravenously (nausea: 50.0% vs 100.0%, P<0.001; vomiting: 8.3% vs 69.5%, P=0.001; diarrhea: 50.0% vs 83.3%, P=0.030). The incidence of oral mucositis and liver or kidney impairments did not differ between the two groups. Post-auto-HSCT efficacy evaluation demonstrated no differences in the percentages of patients obtaining a very good partial response and better outcomes, as well as in the improvement rate to complete remission. With a median follow-up time of 37.9 (31.0 - 49.4) months, the median progression-free survival (PFS) of the oral and injection groups was not reached and 35.9 months (95% CI: 28.3 months-not reached), respectively. Median overall survival (OS) was not reached for either. Neither PFS nor OS reached statistical significance between the two groups. To examine the drug bioavailability, melphalan pharmacokinetics were tested in 6 patients, comprising 3 from the oral group and 3 from the injection group. The result demonstrated that both formulations reached their peak levels in 30 min. Although the oral melphalan exposure on average was 82.2% of the injection dosage form, there was no significant difference in bioavailability. Conclusions: Oral melphalan, as a conditioning regimen for auto-HSCT in paients with MM, demonstrated favorable bioavailability, a low incidence of adverse reactions, and good clinical efficacy.