Search Results (611)

Background and Objectives: Autologous fat transplantation using fat alone can lead to postoperative complications. Laminin–alginate beads have been investigated as carriers for adipose mesenchymal stem cells (ASCs), with the potential to modulate cell release kinetics, influence macrophage responses, and thereby affect the maintenance of graft volume. We hypothesized that encapsulating ASCs in laminin–alginate beads would allow gradual ASC release into the transplantation site and influence the macrophage-related microenvironment during fat graft maturation. Materials and Methods: ASCs were isolated from two female enhanced green fluorescent protein (eGFP) transgenic rats. For SC (ASC + fat) grafts, ASCs were freely mixed with 1 mL of mature adipose tissue. For bead-encapsulated cell (BEC) (laminin–alginate + ASC + fat) grafts, ASCs were first encapsulated in laminin–alginate beads and subsequently mixed with 1 mL of fat tissue. The fat graft was subcutaneously injected into the backs of the rats, which were subsequently euthanized at weeks 4, 6, and 8. The grafts were then harvested for histological and immunofluorescence analyses. Results: The histological analysis indicated that the number of eGFP-ASCs in the BEC grafts gradually increased between weeks 4 and 8, whereas that in the SC grafts decreased over the same period. The BEC grafts also exhibited a numerically higher degree of M2 macrophage infiltration. Conclusions: Laminin–alginate bead encapsulation was associated with prolonged persistence of eGFP-ASCs within the graft area. Although the macrophage-related findings were not statistically significant, they suggest a potential interaction between gradual ASC release and the local graft microenvironment. Full article

Background and Objectives: Relapsed/refractory non-Hodgkin lymphoma (R/R NHL) remains a major therapeutic challenge, particularly in patients with peripheral T-cell lymphomas (PTCL), who frequently exhibit poor responses to salvage therapy and inferior survival outcomes. Achieving adequate disease control before autologous stem cell transplantation (ASCT) is a critical determinant of long-term survival. The bendamustine, gemcitabine, vinorelbine, and prednisolone (BEGEV) regimen has demonstrated high efficacy and favorable tolerability in relapsed/refractory classical Hodgkin lymphoma; however, data regarding its role in NHL are extremely limited. Materials and Methods: We conducted a retrospective, single-center analysis of patients with R/R NHL who received the BEGEV regimen as salvage therapy. Clinical characteristics, response rates, transplantation outcomes, progression-free survival (PFS), overall survival (OS), and safety data were evaluated. Treatment responses were assessed according to standard radiologic response criteria. Survival analyses were performed using the Kaplan–Meier method. Results: A total of 68 patients with R/R NHL were included in the analysis. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype, accounting for 49 patients (72.1%). BEGEV was administered predominantly in later salvage settings. Response assessments were available for 56 patients. Among evaluable patients, the objective response rate (ORR) was 73.2%, whereas the ITT ORR was 60.3% (41/68). Following BEGEV therapy, 25 patients (36.8%) proceeded to autologous stem cell transplantation (ASCT), while 8 patients (11.8%) underwent allogeneic stem cell transplantation (allo-SCT). Exploratory analyses demonstrated longer overall survival (log-rank p = 0.012) and progression-free survival (log-rank p = 0.011) among patients who subsequently underwent transplantation; however, these findings should be interpreted with caution because of the retrospective study design and the potential for selection and immortal time biases. Median PFS and OS were 4 and 26 months, respectively. Adverse events were predominantly hematologic and generally manageable. Conclusions: BEGEV may represent a reasonable salvage regimen for selected patients with R/R NHL and may facilitate disease control allowing subsequent transplantation in selected patients, including selected PTCL patients. Full article

Background: High-dose melphalan 140–200 mg/m² (HDM) with autologous stem cell transplant (ASCT) is standard first-line treatment in multiple myeloma (MM), yet standard BSA-based dosing results in wide variation in systemic exposure (AUC). We developed a pharmacokinetic (PK)-guided dosing strategy using a 100 mg/m² first dose, enabling real-time PK assessment and individualized adjustment for the second dose. We report final results of Phase A of our multi-center Phase 1 trial (NCT04483206, MyMel) evaluating feasibility and accuracy of this personalized approach. Methods: Patients received melphalan 100 mg/m² on Day −3, and seven PK samples were collected and shipped overnight for LC-MS/MS analysis. Real-time AUC estimation using noncompartmental analysis (NCA) guided Day −1 dosing to achieve pre-specified AUC targets (13.5 or 14.5 mg × h/L). For comparison, post hoc Bayesian estimation using a nonlinear mixed effects (NLME) model was performed. Sparse sampling designs were evaluated using NONMEM. Results: All 20 patients successfully received PK-guided dosing, with Day −1 doses determined within 48 h. PK-guided dosing reduced AUC variability (CV 4.20–5.62%), with 19 of 20 achieving AUCs within ±10% of the target, compared to what would have been achieved by BSA dosing (CV 9.74–15.34%). NLME improved accuracy, particularly in patients with missing samples, and maintained performance using only four PK time points. Conclusions: This study demonstrates that PK-guided dosing is accurate and feasible with HDM-ASCT. NLME enhances accuracy and enables simplified sampling. Phase B will identify maximum tolerated systemic exposure of seven additional AUC cohorts using the NLME model and a four-sample design. Full article

Background: Neuroblastoma is a common extracranial solid malignant tumor of early childhood; however, mandibular involvement is rare and may mimic odontogenic or inflammatory disease. Case Presentation: We report an 8-month-old girl with left paramandibular swelling initially suspected to represent parotitis or odontogenic inflammation. Imaging revealed a destructive mandibular lesion with sunburst periosteal reaction, and histology confirmed undifferentiated neuroblastoma. Staging identified a left primary adrenal tumor with extensive bone marrow infiltration and MYCN proto-oncogene amplification. The patient received multimodal high-risk neuroblastoma therapy, including chemotherapy, surgery, autologous stem cell transplantation, proton therapy, antibody therapy, and Lorlatinib. Despite radiological remission, she developed severe pulmonary complications and died shortly before the age of five years. Methods: A focused literature review was conducted to identify published pediatric cases of metastatic neuroblastoma involving the mandible. Results: Through our review, we identified 31 published pediatric cases of mandibular metastatic neuroblastoma. Reported cases most commonly described mandibular swelling, pain, tooth mobility, and facial asymmetry. Most mandibular lesions represented metastatic disease from an adrenal or abdominal primary tumor. Conclusions: Mandibular involvement of neuroblastoma is rare but clinically important. In infants and young children, persistent or atypical (para-/peri)mandibular swelling should not be assumed to be odontogenic or inflammatory. Early imaging, biopsy, and interdisciplinary referral are essential for timely diagnosis and treatment. Full article

Background: Multiple myeloma (MM) is an incurable hematologic malignancy, and the majority of patients eventually relapse due to persistent myeloma cells. While minimal residual disease (MRD) reflects tumor burden, the host immune system also plays a crucial role in disease control. Our study aimed to evaluate MRD, complete blood count (CBC), and immune cell profiles in MM patients treated with bortezomib/adriamycin/dexamethasone (PAD) chemotherapy followed by autologous stem cell transplantation (ASCT) to determine their prognostic value and interplay. Objectives: This study aims to identify markers indicative of a favorable prognosis in MM patients. Methods: CBC data were collected from 93 MM patients at diagnosis, prior to ASCT, and 3 months post-ASCT. Immune cell profiles were assessed via flow cytometry using fresh peripheral blood samples from a subset of 33 prior to ASCT and 3 months post-ASCT. We subsequently investigated the associations between MRD status and prognosis, the predictive value of CBC, and the longitudinal changes in immune cell profiles and their correlation with clinical outcomes. Results: An increased frequency of negative immunomodulatory cell subsets and activated T lymphocytes prior to ASCT were associated with a poor prognosis. Conversely, lower levels of exhausted T lymphocytes, alongside higher levels of functional T cells and marginal zone B cells post-ASCT, predicted a favorable prognosis. Conclusions: Our study demonstrates that pre-ASCT immune status, post-ASCT immune reconstitution, and MRD status at 3 months post-ASCT are closely associated with clinical outcomes in MM patients. These findings underscore the critical importance of regular immune monitoring in the comprehensive management of MM. Full article

Multiple myeloma (MM) is a malignant plasma cell disorder and one of the most common tumors of lymphoid origin. In the process of oncogenesis, there is a significant change in the immune balance in the body, which leads to the suppression of the immune response to the tumor. This immune suppression is one of the reasons why the tumor can progress and cause serious health problems for the patient. One of the key factors that affect immune balance is innate lymphoid cells (ILCs). ILCs play an important role in regulating the immune response and can both promote and hinder the development of tumor processes, depending on their functional state and interaction with other cells of the immune system. Among ILCs, ILC1 mainly exert antitumour activity, but ILC2 and ILC3 are usually protumorigenic. One of the standard treatments for MM is autologous hematopoietic stem cell transplantation (auto-HSCT), and the aim of our study was to evaluate the effect of auto-HSCT on ILCs in MM. We assessed the number and subpopulation composition of ILCs in MM patients before and after auto-HSCT. In MM patients, an increase in the proportion of ILC2 and a decrease in ILC1 are observed before auto-HSCT compared to healthy controls. The subpopulation composition of ILCs changes in patients with multiple myeloma after auto-HSCT, with an increase in ILC1 and a decrease in ILC2 compared to pre-auto-HSCT values. No differences were observed in the relative number of different types of ILC in MM patients after auto-HSCT and in healthy controls. It has been shown that the number of immature CD5⁺ILC2s in the peripheral blood of patients with multiple myeloma is comparable to that of healthy individuals. However, in MM patients, HSCT leads to an increase in the relative number of CD5⁺ILC2s. Full article

Background: Despite improved outcomes with antiretroviral therapy, HIV-associated lymphoma (HAL) remains a major cause of mortality. Autologous stem cell transplant (ASCT) may be curative for relapsed/refractory (R/R) HAL, but HIV-related immunosuppression complicates management. We systematically reviewed prospective evidence on ASCT efficacy and toxicity in HAL. Methods: PubMed, Cochrane, Embase, and ClinicalTrials.gov were searched for publications between 1 January 1996 and 21 June 2026, with an initial search in January 2024 updated in June 2026. Non-English studies, retrospective analyses, studies with fewer than 10 eligible patients, and studies of primary CNS lymphoma were excluded. Studies of first-line ASCT were included for toxicity analysis but excluded from efficacy analysis. Analyses were performed using MedCalc v22.032. Results: 378 titles were screened, 350 underwent abstract review and 40 full-text review. Six non-randomized prospective studies were identified. Identified trials included a total of 134 patients (33 Hodgkin lymphoma, 101 non-Hodgkin lymphoma). Median age and CD4 counts reported by individual studies ranged from 39 to 47 years and 172–279 cells/µL, respectively; 94.2% of patients were male. All patients received antiretroviral therapy at time of ASCT. Pooled six-month non-relapse mortality (NRM) was 5.39% (95% CI: 2.28–9.73). Among the 52 R/R HAL patients with survival data available, estimated 2-year overall survival (OS) and progression-free survival (PFS) were 79.8% (95% CI: 68.1–89.3) and 77.9% (95% CI: 65.9–87.8), respectively. Conclusions: In this first systematic review and meta-analysis of ASCT for HAL, NRM post-ASCT is consistent with historical trial results in the non-HIV population. OS and PFS are encouraging, but prospective data are limited and comparative data is absent. Full article

Background: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is an established salvage therapy for relapsed or refractory (R/R) germ cell tumors (GCTs). Methods: We conducted a retrospective analysis of 9 patients (23–41 years of age) with relapsed/refractory (R/R) GCTs treated according to the Swedish–Norwegian Testicular Cancer Group Clinical Protocol (SWENOTECA), at the Specialized Hospital for Active Treatment of Hematological Diseases (SHATHD) in Sofia, Bulgaria. The study evaluates the efficacy and safety of HDCT followed by ASCT in R/R GCTs eligible for second-line consolidation. The cohort was predominantly high-risk, with 77.7% of patients exhibiting stable or progressive disease (SD/PD) after first-line platinum therapy. Response was assessed via RECIST 1.1 criteria and tumor marker monitoring. Results: Median OS and PFS were 8.4 and 5.9 months, respectively. While the ORR post-ASCT was 33.3% (all CR), the 2-year survival plateau (33.3%) suggests curative potential in a subset of patients. Notably, there was no treatment-related mortality (TRM). Conclusions: Tandem HDCT is a feasible salvage strategy with manageable toxicity and no TRM in this small, heavily pre-treated cohort. Although efficacy results are exploratory due to the limited number of patients, the observed long-term remissions confirm the curative potential of this standard-of-care consolidation in a real-world clinical setting. Full article

First-line (1L) therapy for mantle cell lymphoma (MCL) continues to evolve rapidly, with several recent phase II and phase III trials consistently showing the activity of novel covalent Bruton’s tyrosine kinase inhibitor (cBTKi) combinations. Historical treatment selection criteria such as patient age, fitness, and eligibility for autologous stem cell transplantation generally remain applicable for some, but not all, of these novel regimens. This potential for flexibility necessitates the consideration of additional factors during decision-making, such as MCL biology, patient risk tolerance, logistical and resource implications, and the impact on use of later-line options. This paper presents three illustrative patient cases to explore 1L therapy selection among these new and emerging cBTKi options. The realized and anticipated benefits, limitations, and challenges and persisting evidence gaps associated with these regimens are discussed. Full article

Peripheral nerve injuries (PNI) present a major clinical and socioeconomic challenge due to limited regenerative capacity. Adipose-derived stem cells (ADSCs) within the stromal vascular fraction (SVF) of white adipose tissue offer a promising autologous source for regenerative support. This study evaluated the impact of mechanical processing CELT (Cell-Enriched Lipotransfer) and CELT^PLUS and electrical stimulation on the regenerative secretome of human lipoaspirates. qPCR analysis revealed that CELT^PLUS processing, which incorporates mechanical intersyringe shifting, significantly doubled the gene expression of nerve growth factor (NGF) (p = 0.015), vascular endothelial growth factor (VEGF) (p = 0.02), and brain-derived neurotrophic factor (BDNF) (p = 0.04) compared to CELT-processed lipoaspirate. Protein analysis via ELISA confirmed a time-dependent secretion of NGF and VEGF over 96 h. Furthermore, 24 h electrical stimulation (2 V) significantly enhanced NGF protein release (p < 0.001). These findings demonstrate that standardized mechanical processing effectively enriches regenerative cell populations and amplifies their neurogenic and angiogenic potential. The additional modulation of growth factor secretion via electrical stimulation highlights the potential of processed adipose tissue as a functional, autologous transplant for enhanced nerve reconstruction. Full article

Genetically modified hematopoietic stem cell therapy using gene-modified autologous hematopoietic stem cells has evolved over the last 30 years as an alternative approach to circumvent the limitations of donor availability, risks of excessive regimen related toxicity, prolonged immune suppression and graft-versus-host disease associated with allogeneic hematopoietic cell transplantation. Gene replacement therapy based on viral insertion of transgene into host genome was developed as one of the main methods for gene modification of autologous cells. Unfortunately, many cases of oncogenesis were directly caused by genetically modified hematopoietic stem cell therapy. The purpose of the present review is the description of cases of leukemogenesis in gene replacement therapy in hematopoietic stem cells, elucidation of the causes, and overview of the risk mitigation strategies. It aims to elucidate the main risk factors in gene replacement therapy in hematopoietic stem cells. The insertional mutagenesis leads to activation of proto-oncogenes, mostly LMO2 and MECOM-EVI1. γ-retroviral vectors are dangerous in this case, as they contain long terminal repeats with strong promotor activity and are prone to integration near transcription initiation sites. Therefore, safer self-inactivating lentiviral vectors were developed, with long terminal repeats modified to reduce their promoter activity and with safer integration pattern. Nevertheless, the risk of leukemogenesis remains because the promoter integrated into the transgene expression cassette may still influence nearby gene expression. Another risk factor is monosomy 7, either pre-existing or caused by MECOM-EVI1 activation, which may contribute directly to leukemogenesis. Thus, oncogenesis in HSPC gene replacement therapy does not have a single definitive cause; rather, multiple factors may contribute, and each may be sufficient under specific conditions. Full article

Background: This review aims to provide a comprehensive and practical overview of the evolving role of autologous transplantation in leukaemias, a strategy that was once largely abandoned but has recently regained interest in selected clinical settings. Methods: We reviewed the historical development of autologous transplantation in acute leukaemias, including the early period during which autologous transplantation was considered inferior to allogeneic approaches because of limited graft purification techniques and the inability to induce effective graft-versus-leukaemia (GVL)-like immune responses. We further summarise more recent experimental strategies aimed at improving stem cell purification and enhancing anti-leukaemic immune activity in autologous settings. In addition, we discuss how advances in measurable residual disease (MRD) assessment and molecular risk stratification have contributed to the renewed interest in autologous transplantation in selected subgroups of leukaemia patients. Results: This review identifies clinical situations in which autologous transplantation remains an important therapeutic option, including plasma cell leukaemia, where it continues to represent a standard first-line approach. We also discuss well-defined patient subgroups, particularly selected AML subtypes with intermediate-risk molecular profiles and acute promyelocytic leukaemia (APL) in second remission, in which outcomes following autologous transplantation may be comparable to, or occasionally superior to, those achieved with allogeneic transplantation. In contrast, autologous transplantation currently plays only a limited role in diseases such as chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML). Although attempts to induce potent anti-leukaemic immune effects in autologous settings have so far shown limited clinical efficacy, several emerging strategies appear promising and may further expand the role of autologous transplantation, particularly in elderly or frail patients. Discussion: Overall, current molecular and MRD-based risk stratification strategies, together with emerging immunological and graft-manipulation approaches, may redefine the role of autologous transplantation as a personalised therapeutic option in selected subgroups of leukaemia patients. Full article

Background: Whether patients with relapsed multiple myeloma (MM) should proceed directly to a second autologous stem cell transplantation (ASCT2) or receive re-induction chemotherapy beforehand remains uncertain. In real-world practice, treatment allocation is highly heterogeneous, and comparative data addressing the impact of pre-ASCT2 strategy on survival outcomes are limited, partly because ASCT2 is reserved for selected patients and is not routinely performed in all relapsed MM cases. We aimed to evaluate real-world outcomes of ASCT2 performed either directly at relapse or following re-induction chemotherapy in patients with relapsed MM, with a focus on progression-free survival after ASCT2 (PFS2) and overall survival (OS). Methods: We conducted a multicenter retrospective cohort study including 42 patients with relapsed MM who underwent ASCT2 between 2012 and 2024 across eight centers. Patients were grouped according to pre-ASCT2 management: those proceeding directly to ASCT2 without additional systemic therapy (direct-ASCT2, n = 21) and those receiving ≥ 1 line of salvage chemotherapy prior to ASCT2 (re-induction, n = 21). Survival outcomes were estimated using Kaplan–Meier methods and explored using multivariable Cox regression analyses. Results: The median PFS2 for the entire cohort was 19.7 months (95% CI, 7.8–31.6), with no statistically significant difference between the direct-ASCT2 and re-induction groups (21.3 vs. 13.8 months; p = 0.790). Median OS was 48.2 months (95% CI, 41.3–55.1). Although OS was significantly longer in the unadjusted analysis (51.7 vs. 39.6 months; p = 0.019), this difference was not maintained after multivariable adjustment. Post-ASCT2 response rates were comparable between groups, and day-100 transplant-related mortality was low at 2.4%. Conclusions: In this multicenter real-world cohort, pre-ASCT2 re-induction chemotherapy was not associated with a clear improvement in PFS2 compared with proceeding directly to ASCT2. Observed differences in unadjusted OS likely reflect confounding by indication and selection bias inherent to retrospective treatment allocation. These findings should therefore be interpreted as hypothesis-generating, but they add to the limited real-world evidence base on ASCT2, a salvage strategy that is typically applied to highly selected patients. Full article

Background: β-haemoglobinopathies, including sickle cell disease and transfusion-dependent β-thalassaemia, are among the most common monogenic disorders worldwide and represent a major global health burden. Conventional treatments, such as blood transfusions, iron chelation, fetal haemoglobin induction, and allogeneic haematopoietic stem cell transplantation, have improved outcomes but remain limited by treatment-related toxicity, donor availability, and incomplete curative potential. Methods: A narrative literature review was conducted using PubMed up to 2025. Search terms included “sickle cell disease,” “sickle cell anemia,” “β-thalassemia,” “transfusion-dependent beta-thalassemia,” “gene therapy,” “gene addition,” “gene editing,” “CRISPR-Cas9,” “lentiviral vector,” “children,” “paediatric,” and “pediatric.” Relevant clinical trials, reviews, consensus statements, and guidelines were selected and qualitatively analysed. Results: Gene therapy for β-haemoglobinopathies is based mainly on two strategies: gene addition and gene editing. Gene addition uses lentiviral vectors to introduce functional or modified β-globin genes into autologous haematopoietic stem cells, whereas gene editing targets regulatory pathways, particularly BCL11A, to reactivate fetal haemoglobin synthesis or correct disease-causing mutations. Clinical studies have shown encouraging outcomes, including transfusion independence in many patients with β-thalassaemia and marked reduction or elimination of vaso-occlusive crises in sickle cell disease. Paediatric and adolescent data are increasingly promising, although still limited. Conclusions: Gene therapy is reshaping the treatment landscape of β-haemoglobinopathies by offering a personalised and potentially curative approach. However, long-term safety, conditioning toxicity, fertility preservation, accessibility, costs, and implementation in high-prevalence regions remain critical challenges. Further studies are needed to optimise patient selection and expand equitable access. Full article

Background: BCMA-targeted Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of Relapsed/Refractory Multiple Myeloma (RRMM). However, the disease is not curable and progression after CAR T-cell treatment remains a challenge. Clonal hematopoiesis, specifically mutations in the DNA damage response gene PPM1D, has been linked to therapy resistance and inferior survival in lymphoma patients undergoing cellular therapy. The impact of PPM1D mutations on MM patient outcome after CAR T-cell therapy remains undefined. Methods: We conducted a retrospective single-center study of 83 patients with RRMM patients treated with idecabtagene vicleucel or ciltacabtagene autoleucel between 2022 and 2025. Next-generation sequencing was performed on peripheral blood mononuclear cells collected prior to CAR T-cell infusion to identify PPM1D exon 6 mutations (variant allele frequency > 0.01). We analyzed associations between mutational status, clinical characteristics, toxicity, and survival. Results: PPM1D mutations were detected in 14.5% (12/83) of patients. PPM1D-mutated patients had fewer prior autologous stem cell transplantation compared to wild-type patients (50% vs. 82%, p = 0.02) and presented more advanced disease burden and adverse prognostic features (R-ISS stage III 58% vs. 20%, p = 0.05). Notably, PPM1D status did not impact initial efficacy; complete remission rates were comparable between groups (67% vs. 69%). However, PPM1D mutations were significantly associated with inferior progression-free survival (PFS) (median PFS: 6 months vs. 16 months, p = 0.04). Regarding toxicity, the mutated subgroup exhibited significantly higher rates of grade ≥2 cytokine release syndrome and a trend toward increased neurotoxicity (25% vs. 7%). Conclusions: PPM1D clonal hematopoiesis is frequent in RRMM and despite deep initial responses, patients harboring PPM1D mutations face a significantly higher risk of early relapse. PPM1D mutations may serve as a biomarker for poor durability of response and should be further evaluated in larger, prospective trials. Full article