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Keywords = autologous bone marrow transplantation

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13 pages, 766 KiB  
Article
Combined Minimal Residual Disease Evaluation in Bone Marrow and Apheresis Samples in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation Improves Outcome Prediction
by Irene Attucci, Benedetta Peruzzi, Chiara Nozzoli, Serena Guerrieri, Sofia Pilerci, Riccardo Boncompagni, Serena Urbani, Chiara Orazzini, Sara Bencini, Manuela Capone, Maria Messeri, Roberto Caporale, Francesco Annunziato, Alessandro M. Vannucchi and Elisabetta Antonioli
Cancers 2025, 17(15), 2439; https://doi.org/10.3390/cancers17152439 - 23 Jul 2025
Viewed by 228
Abstract
Introduction: Despite the approval of novel agents that have significantly improved long-term survival rates for multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT), most patients eventually relapse. The failure to achieve or maintain bone marrow (BM) minimal residual disease (MRD) [...] Read more.
Introduction: Despite the approval of novel agents that have significantly improved long-term survival rates for multiple myeloma (MM) patients undergoing autologous stem cell transplant (ASCT), most patients eventually relapse. The failure to achieve or maintain bone marrow (BM) minimal residual disease (MRD) negativity is a recognised adverse prognostic factor for progression-free survival (PFS) and overall survival (OS). Contamination of stem cell apheresis by clonal plasma cells may also affect prognosis, though data remain limited. Methods: We conducted a prospective, single-centre observational study including 100 newly diagnosed MM patients eligible for ASCT and treated with bortezomib-based triplet induction. MRD was assessed both on BM and apheresis samples using multiparameter flow cytometry (MFC-MRD) with a sensitivity of 10−5. Results: Clonal plasma cells were detected in 22 apheresis samples (aMRD+), all of which were associated with BM MRD positivity. Patients with aMRD+ had inferior pre-ASCT responses (≥VGPR: 10% vs. 63%, p = 0.005) and worse post-ASCT BM MRD negativity rates (4% vs. 49%, p = 0.048). After a median follow-up of 52.4 months, aMRD+ was associated with shorter progression-free survival (median 38.5 vs. not reached, p = 0.007) and overall survival (median 60 months vs. not reached, p = 0.003). Conclusions: Contamination of the apheresis product is associated with persistent BM disease and poorer outcomes. Combined MRD assessment in both bone marrow and apheresis may improve risk stratification in MM patients undergoing ASCT. Full article
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14 pages, 731 KiB  
Article
Enhancing Bone–Cartilage Interface Healing in Osteochondral Autograft Transplantation: Effects of BMAC Augmentation and Rehabilitation Protocols
by Robert Gherghel, Ilie Onu, Ana Onu, Ioana-Irina Rezus, Ovidiu Alexa, Daniel Andrei Iordan, Luana Andreea Macovei and Elena Rezus
Life 2025, 15(7), 1066; https://doi.org/10.3390/life15071066 - 3 Jul 2025
Viewed by 455
Abstract
This study aimed to evaluate the effectiveness of different rehabilitation protocols following osteochondral autograft transplantation (OAT) in patients with focal osteochondral defects of the femoral condyle, using the MOCART 2.0 knee score as a primary imaging outcome. Twenty-nine patients were divided into three [...] Read more.
This study aimed to evaluate the effectiveness of different rehabilitation protocols following osteochondral autograft transplantation (OAT) in patients with focal osteochondral defects of the femoral condyle, using the MOCART 2.0 knee score as a primary imaging outcome. Twenty-nine patients were divided into three groups: Group 1 (n = 9) received OAT with bone marrow aspirate concentrate (BMAC) and a 12-week two-phase rehabilitation program; Group 2 (n = 11) received OAT with a 12-week program without BMAC; and Group 3 (n = 9) received OAT with a shortened 6-week program. At the 12-month follow-up, Group 1 demonstrated a superior cartilage repair quality, with the highest mean MOCART 2.0 score (96.1), compared to Group 2 (80.2) and Group 3 (71.7). Notably, complete defect filling was observed in five patients in Group 1 versus four in Group 2 and only one in Group 3. The integration and surface integrity were also better preserved in Group 1. The addition of BMAC and an extended, progressive rehabilitation protocol significantly enhanced the morphological cartilage repair parameters. These results suggest that a biologically enhanced and prolonged recovery plan may offer a greater structural restoration of cartilage after OAT than conventional or accelerated protocols. Full article
(This article belongs to the Special Issue Recent Advances in Physiotherapy for Musculoskeletal)
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15 pages, 722 KiB  
Article
Evaluation of Interleukin-10, Vascular Endothelial Growth Factor Levels, and Bone Marrow Parameters in Multiple Myeloma Patients at Diagnosis and After Treatment
by Fulya Memis, Meryem Yalvac Kandefer, Sonay Aydin, Klara Dalva and Selami Kocak Toprak
Diagnostics 2025, 15(13), 1641; https://doi.org/10.3390/diagnostics15131641 - 27 Jun 2025
Viewed by 404
Abstract
Background: Interleukin-10 (IL-10) and vascular endothelial growth factor (VEGF) are believed to possess a role in the pathophysiology of multiple myeloma (MM). We aimed to assess the significance of these parameters in the diagnosis, monitoring, and prognosis of the disease by examining them [...] Read more.
Background: Interleukin-10 (IL-10) and vascular endothelial growth factor (VEGF) are believed to possess a role in the pathophysiology of multiple myeloma (MM). We aimed to assess the significance of these parameters in the diagnosis, monitoring, and prognosis of the disease by examining them in patients at diagnosis and post-treatment and comparing the findings with those of healthy individuals. Methods: We conducted blood sampling from 35 patients diagnosed with MM at the time of diagnosis and from 15 of these patients post-treatment. We additionally assessed similar serum markers in a control group of 15 healthy individuals. Furthermore, we documented laboratory results, organ involvement, comorbidities, and CD27-CD81 levels assessed using flow cytometry in the bone marrow, along with treatments and patient responses. We also examined the quantity of cells collected during mobilization in patients who had autologous stem cell transplantation. Results: We found a positive correlation (p = 0.028/p = 0.035) between IL-10 and VEGF with the international staging score. In patients with renal involvement, IL-10 levels were higher and VEGF levels were lower than those without renal involvement (p = 0.011/p = 0.012). We showed that VEGF levels decreased significantly with treatment (p = 0.001). We found no statistically significant correlation between treatment responses and IL-10 and VEGF. The number of CD34 cells collected by mobilization showed a negative correlation with CD27 and a positive correlation with VEGF (p = 0.007/p = 0.032). Conclusions: Serum IL-10 level is associated with ISS and renal involvement in MM patients. There is a positive correlation between serum VEGF levels and the number of stem cells collected during mobilization. As CD27 expression increases, the number of stem cells collected in mobilization decreases. Full article
(This article belongs to the Special Issue Advances in Laboratory Analysis and Diagnostics)
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12 pages, 744 KiB  
Article
Feasibility Assessment of Autologous Human Immune System (HIS) ImmunoGraft Platform Development Using Autologous Mobilized Peripheral Blood (MPB) CD34 Cells Derived from Adult HNSCC Patient
by Bhavna Verma, Georgia Zhuo Chen, Edmund K. Waller, Mihir Patel, Allyson Anderson, Neal Goodwin, Amy Wesa, Yong Teng and Nabil F. Saba
Int. J. Mol. Sci. 2025, 26(11), 5269; https://doi.org/10.3390/ijms26115269 - 30 May 2025
Viewed by 523
Abstract
Humanized mice generated by hematopoietic stem cell (HSC) transplantation are limited by the immune system developed being allogeneic to the tumor. We have innovated a platform to reconstitute an autologous human immune system (HIS) in immunodeficient NOG-EXL mice from mobilized peripheral blood (MPB)-CD34 [...] Read more.
Humanized mice generated by hematopoietic stem cell (HSC) transplantation are limited by the immune system developed being allogeneic to the tumor. We have innovated a platform to reconstitute an autologous human immune system (HIS) in immunodeficient NOG-EXL mice from mobilized peripheral blood (MPB)-CD34 cells, along with PDX generated from the same patient’s tumor tissue. Patients consented under an IRB-approved protocol for tumor biopsy and HSC apheresis at Emory University. HSC collection included mobilization with G-CSF and plerixafor, immunomagnetic bead isolation with CliniMACS, and cryopreservation of CD34+ cells. PDX were established from biopsies or surgical specimens by passaging into immunodeficient mice. Irradiated NOG-EXL mice were engrafted with HSCs by intravenous transplantation of CD34+ HSC. Engraftment of human T cells, B cells, and myeloid cells in peripheral blood was assessed by serial flow cytometry of blood samples, with final assessment of immune components in spleen and bone marrow at 30 weeks. Twenty-eight PDX models were generated from 43 patients with HNSCC; 1 patient underwent apheresis. HSC engraftment in blood was observed in 100% of NOG-EXL mice at 8 weeks post-transplant, with 5–20% hCD45+ cells present in the periphery. B-cell development was predominant at early time points and declined over time. Human T-cell and subset development of CD4+ and CD8+ T cells were observed in blood from 15 weeks post-transplant. Strong development of the myeloid lineage (CD33+) was observed starting at 8 weeks and persisted throughout the study. These data demonstrate that mobilization and apheresis of HNSCC patients is technically and clinically feasible and may allow the establishment of autologous HIS-PDX mice. Full article
(This article belongs to the Section Molecular Immunology)
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11 pages, 624 KiB  
Case Report
Effects of a Concurrent Mixed-Modality (Telerehabilitation and Face-to-Face) Exercise Rehabilitation Program in a Patient with Multiple Myeloma Prior to Spinal Cord Transplantation: A Case Study
by Juan Carlos Hernández-Sigüenza, Paula Blanco-Gimenez, Luis Baraja-Vegas, Josep López-Soler, Francisco Javier Falaguera-Vera, Eloy Jaenada-Carrilero and Juan Vicente-Mampel
Curr. Oncol. 2025, 32(5), 282; https://doi.org/10.3390/curroncol32050282 - 16 May 2025
Viewed by 511
Abstract
Introduction: Multiple myeloma constitutes approximately 12% of hematologic malignancies and predominantly affects older adults, significantly compromising their quality of life. Although exercise interventions have shown benefits in oncology, evidence specific to MM remains limited and of low certainty. The presence of complex comorbidities [...] Read more.
Introduction: Multiple myeloma constitutes approximately 12% of hematologic malignancies and predominantly affects older adults, significantly compromising their quality of life. Although exercise interventions have shown benefits in oncology, evidence specific to MM remains limited and of low certainty. The presence of complex comorbidities in MM patients necessitates highly individualized approaches. Prehabilitation has emerged as a promising strategy to enhance functional capacity prior to autologous stem cell transplantation. This case study evaluates the feasibility of a personalized, scheduled exercise intervention delivered via telerehabilitation. Intervention: This case study seeks to examine the feasibility of implementing a personalized and scheduled exercise intervention within a telerehabilitation framework for a medically complex patient with multiple myeloma (MM). The 12-week prehabilitation protocol is designed to enhance physical function prior to autologous bone marrow transplantation by integrating therapeutic exercise targeting key parameters related to quality of life and clinical resilience, such as muscular strength, aerobic capacity, coordination, and overall well-being. The intervention includes concurrent training (strength and aerobic exercises) delivered 2–3 times per week, with aerobic activities conducted independently at home through a virtual format. Assessments were performed at baseline and post-intervention. Results and conclusion: A personalized exercise program, implemented through a hybrid model of in-person and telerehabilitation, is both feasible and safe. It has the potential to enhance physical function and quality of life in patients with multiple myeloma. Further research is necessary to validate these findings across broader patient populations. Full article
(This article belongs to the Section Hematology)
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18 pages, 2990 KiB  
Article
Prognostic Value of Post-Transplant MRD Negativity in Standard Versus High- and Ultra-High-Risk Multiple Myeloma Patients
by Lea Jasmin Kündgen, Dilara Akhoundova, Michele Hoffmann, Myriam Legros, Inna Shaforostova, Katja Seipel, Ulrike Bacher and Thomas Pabst
Cancers 2025, 17(9), 1565; https://doi.org/10.3390/cancers17091565 - 4 May 2025
Viewed by 746
Abstract
Background: Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) [...] Read more.
Background: Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) and overall survival (OS). However, the impact of MRD remains poorly characterized in MM patients with high- or ultra-high-risk cytogenetics. Objectives: This study investigated the prognostic value of post-transplant MRD in standard- versus high- and ultra-high-risk MM. To this aim, we performed a retrospective analysis of 137 MM patients who underwent high-dose chemotherapy (HDCT) and ASCT at our institution between January 2019 and December 2021. Cytogenetics were assessed by fluorescence in situ hybridization. High-risk genomic alterations included del(17p), t(4;14), t(14;16), t(14;20), gain(1q), and TP53 mutations, with two or more alterations defining the ultra-high-risk category. MRD was assessed in bone marrow aspirates post-ASCT using flow cytometry. Results: Eighty-two (60%) patients were categorized as being at standard risk, forty (29%) as high risk, and fifteen (11%) as ultra-high risk. Median follow-up was 47 months. MRD negativity was achieved in 76 (55%) patients. At 48 months, the overall PFS rate was 61% (72%, 50%, and 32% for the standard-, high-, and ultra-high-risk subgroups, respectively; p = 0.0004), while the OS rate was 85% (89%, 79%, and 80% in standard-, high-, and ultra-high-risk MM patients, respectively; p = 0.1494). Within the standard-risk subgroup, longer PFS was observed for patients achieving MRD negativity (p = 0.0172). High- and ultra-high-risk patients showed no significant differences in PFS when stratified by MRD status, possibly due to prompt progression to MRD positivity. Conclusions: Our results suggest that high- and ultra-high-risk MM patients might benefit from closer response monitoring, including dynamic MRD assessment. Further, high- and ultra-high-risk patients might require a more intensive peri-transplant treatment. Full article
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14 pages, 1718 KiB  
Article
The Role of the Bone Marrow Microenvironment in Physical Function and Quality of Life in Patients with Multiple Myeloma After First-Line Treatment with Novel Agents and Autologous Transplantation
by Polyxeni Spiliopoulou, Pantelis Rousakis, Chrysanthi Panteli, Evangelos Eleutherakis-Papaiakovou, Magdalini Migkou, Nikolaos Kanellias, Ioannis Ntanasis-Stathopoulos, Panagiotis Malandrakis, Foteini Theodorakakou, Despina Fotiou, Evangelos Terpos, Vassilios Myrianthopoulos, Maria Gavriatopoulou, Ourania E. Tsitsilonis, Efstathios Kastritis, Meletios Athanasios Dimopoulos and Gerasimos Terzis
Onco 2025, 5(2), 21; https://doi.org/10.3390/onco5020021 - 1 May 2025
Viewed by 880
Abstract
Background/Objectives: Multiple myeloma is a malignancy of plasma cells detected in the bone marrow, inducing symptoms like anemia, hypercalcemia, renal problems, and bone fractures in multiple myeloma patients, affecting their quality of life. The bone marrow microenvironment plays a crucial role in the [...] Read more.
Background/Objectives: Multiple myeloma is a malignancy of plasma cells detected in the bone marrow, inducing symptoms like anemia, hypercalcemia, renal problems, and bone fractures in multiple myeloma patients, affecting their quality of life. The bone marrow microenvironment plays a crucial role in the prognosis and progression of the disease. The purpose of this study was to examine the relationship between the percentages of the major cell populations of the bone marrow, including immune cells, and physical function/quality of life in multiple myeloma patients after first-line treatment. Methods: Twenty-one multiple myeloma patients (N = 14 men, N = 7 women) participated in the study after completing first-line treatment. Bone marrow and blood samples were taken one hundred days after transplantation, while physical function (6 min walking test, handgrip test, maximal aerobic power, and isometric strength), health-related quality of life (QLQ-C30), and body composition (DXA) were assessed 2–5 days later. Flow cytometry was used to assess the percentages of plasma cells, mast cells, B cells (total, precursors, naïve, and memory), T cells (total, CD27− and CD27+), NK/NKT cells (total, CD27− and CD27+), eosinophils, monocytes, neutrophils, myeloid progenitors, erythroblasts, and erythroid progenitors, expressed as percentages of total nucleated cells of the bone marrow. Results: The percentage of CD27+ NK/NKT cells was correlated with five parameters of the quality of life questionnaire: physical function (r = 0.78, p = 0.005), role functioning (r = 0.69, p = 0.020), fatigue (r = −0.86, p = 0.000), pain (r = 0.68, p = 0.021), and dyspnea (r = −0.80, p = 0.003). Conclusions: In conclusion, stronger immune surveillance in the bone marrow from CD27+ NK/NKT cells is correlated with better quality of life in multiple myeloma patients. Full article
(This article belongs to the Special Issue Targeting of Tumor Dormancy Pathway)
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9 pages, 1812 KiB  
Case Report
Venetoclax Plus CyBorD Induction Therapy and Venetoclax Maintenance Treatment for Immunoglobulin Light Chain Amyloidosis with t(11;14) Translocation
by Gréta Garami, Omar Obajed Al-Ali, István Virga, Anita Gulyás, Judit Bedekovics, István Tornai, Árpád Illés and Ferenc Magyari
Curr. Oncol. 2025, 32(2), 63; https://doi.org/10.3390/curroncol32020063 - 26 Jan 2025
Viewed by 1162
Abstract
Background: A total of 50% of patients with AL amyloidosis have t(11;14) translocation, allowing us to use the selective oral BCL-2 inhibitor venetoclax in their treatment. Case presentation: Our patient was admitted to the gastroenterology department due to weight loss and [...] Read more.
Background: A total of 50% of patients with AL amyloidosis have t(11;14) translocation, allowing us to use the selective oral BCL-2 inhibitor venetoclax in their treatment. Case presentation: Our patient was admitted to the gastroenterology department due to weight loss and abdominal pain. An abdominal CT scan revealed some enlarged lymph nodes; therefore, he was referred to the hematology department. A bone marrow biopsy showed massive amorphous amyloid deposition. The sample was positive on Congo red staining and exhibited double refraction under a polarized light microscope. Serum-free light chains and the difference between involved and uninvolved free light chains (dFLCs) were elevated. Using fluorescent in situ hybridization, we detected t(11;14) translocation. Further examinations confirmed the involvement of the liver, colon and heart. Stage II AL amyloidosis was confirmed. Our patient received combined induction therapy with CyBorD and venetoclax due to the presence of the t(11;14) translocation. After six cycles, the patient achieved complete remission. Autologous stem cell transplantation (ASCT) was performed. At 100 days post-ASCT, the patient had complete hematologic remission. Venetoclax maintenance treatment was initiated. The follow-up examinations showed that the patient is in very good partial remission. Conclusions: In the case of our AL amyloidosis patient with t(11;14) translocation, the combined treatment with CyBorD and venetoclax was well tolerated and effective. Full article
(This article belongs to the Section Hematology)
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12 pages, 993 KiB  
Article
Mixed T-Cell Chimerism Following Hematopoietic Cell Transplantation for Non-Malignant Disorders Is Common, Facilitates Anti-Viral Immunity, and Is Not Associated with Graft Failure in Pediatric Patients
by Rubiya Nadaf, Helena Lee, Denise Bonney, Ramya Hanasoge-Nataraj, Srividhya Senthil, Claire Horgan, Malcolm Guiver, Kay Poulton and Robert Wynn
Cells 2024, 13(24), 2119; https://doi.org/10.3390/cells13242119 - 20 Dec 2024
Cited by 1 | Viewed by 1065
Abstract
Myeloid chimerism better reflects donor stem cell engraftment than whole-blood chimerism in assessing graft function following allogeneic hematopoietic stem cell transplant (HCT). We describe our experience with 130 patients aged younger than 18 years, treated with allogeneic HCT using bone marrow or PBSC [...] Read more.
Myeloid chimerism better reflects donor stem cell engraftment than whole-blood chimerism in assessing graft function following allogeneic hematopoietic stem cell transplant (HCT). We describe our experience with 130 patients aged younger than 18 years, treated with allogeneic HCT using bone marrow or PBSC from HLA-matched donors for non-malignant diseases, whose pre-transplant conditioning therapy included alemtuzumab and who were monitored with lineage-specific chimerism after transplant. At 6 years post-transplant, overall survival (OS) was 91.1% and event-free survival (EFS) was 81.5%, with no grade III-IV acute GvHD or chronic GVHD observed. Recipient T-cells did not contribute to graft loss. Mixed T-cell chimerism (MC) did not affect EFS, and there was no connection between T-cell chimerism and myeloid chimerism in patients with MC or graft loss. MC significantly correlated with virus infection; more children with MC were CMV seropositive than those with complete chimerism (CC). Additionally, MC was more common in patients with CMV viramia post-transplant. CD8 T-cell reconstitution was affected by viral reactivation, including CMV, with CD8 T-cell counts higher in the MC group than in the CC group. Mixed T-cell chimerism is due to autologous, virus-specific, predominantly CD8, T-cell expansion, and is protective and not deleterious to the recipient. Full article
(This article belongs to the Special Issue State of the Art and Future Prospects in Stem Cell Transplantation)
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17 pages, 740 KiB  
Article
A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell Transplant
by Richard LeBlanc, Stéphanie Thiant, Rafik Terra, Imran Ahmad, Jean-Sébastien Claveau, Nadia Bambace, Léa Bernard, Sandra Cohen, Jean-Sébastien Delisle, Silvy Lachance, Thomas Kiss, Denis-Claude Roy, Guy Sauvageau and Jean Roy
Curr. Oncol. 2024, 31(11), 7258-7274; https://doi.org/10.3390/curroncol31110535 - 16 Nov 2024
Viewed by 1899
Abstract
Background: To date, the only potential curative treatment for multiple myeloma (MM) remains allogeneic (allo) hematopoietic cell transplant (HCT), although, most patients will eventually relapse. In relapsed patients, donor lymphocyte infusions (DLIs) have been reported to control disease, but the optimal strategy prior [...] Read more.
Background: To date, the only potential curative treatment for multiple myeloma (MM) remains allogeneic (allo) hematopoietic cell transplant (HCT), although, most patients will eventually relapse. In relapsed patients, donor lymphocyte infusions (DLIs) have been reported to control disease, but the optimal strategy prior to and doses of DLIs remain unclear. With this study (NCT03413800), we aimed to investigate the efficacy and toxicity of lenalidomide and dexamethasome (Len/Dex) followed by escalating pre-determined doses of DLIs in MM patients who relapsed after allo HCT. Methods: Patients aged 18–65 years with relapsed MM following upfront tandem autologous (auto)/allo HCT were eligible. Treatment consisted of six cycles of Len/Dex followed by three standardized doses of DLIs: 5 × 106 CD3+/kg, 1 × 107/kg and 5 × 107/kg every 6 weeks. Bone marrow minimal measurable disease (MRD) using flow cytometry (10−5) was performed at enrolment, then every 3 months for 2 years or until disease progression, in a subset of patients. The primary endpoint was efficacy as measured by progression-free survival (PFS) at 2 years following Len/Dex/DLIs. Secondary objectives were safety including GVHD, response including MRD status and overall survival (OS). Results: A total of 22 patients participated in this study, including 62% with high-risk cytogenetics. With a median follow-up of 5.3 years (range: 4.1–6.1), PFS and OS were 26.5% (95% CI: 10.4–45.9%) and 69.2% (95% CI: 43.3–85.1%), respectively. Overall, the best responses achieved post-Len/Dex + DLIs were complete remission in 9.1%, very good partial response in 50%, and progressive disease in 40.9%. Among the nine patients tested for MRD, only two achieved a negative status after receiving DLIs. Six patients died, all due to disease progression. No acute GVHD was observed after DLIs. We report a very low incidence of moderate/severe chronic GVHD of 18.2% with no need for systemic immunosuppressants one year after diagnosis. No unexpected adverse events were observed. Interestingly, a positive correlation between response to Len/Dex re-induction and response to DLIs was found (p = 0.0032). Conclusions: Our findings suggest that Len/Dex/DLIs in second line treatment after upfront tandem auto/allo HCT in relapsed MM patients remains feasible and safe. With a potential correlation between induction chemotherapy and DLI responses, more potent induction regimens together with higher doses of DLIs should be considered in the future. Full article
(This article belongs to the Section Cell Therapy)
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14 pages, 2787 KiB  
Article
Bone Marrow-Suppressive Treatment in Children Is Associated with Diminished IFN-γ Response from T Cells upon Polyclonal and Varicella Zoster Virus Peptide Stimulation
by Eva Tiselius, Emil Sundberg, Hanna Andersson, Anna Höbinger, Peter Jahnmatz, Arja Harila, Josefine Palle, Anna Nilsson and Shanie Saghafian-Hedengren
Int. J. Mol. Sci. 2024, 25(13), 6960; https://doi.org/10.3390/ijms25136960 - 26 Jun 2024
Cited by 1 | Viewed by 1917
Abstract
Severe haematological diseases and lymphoid malignancies require bone marrow (BM)-suppressive treatments. Knowledge regarding the impact of BM-suppressive treatments on children’s memory T cells is very limited. Memory T cells play a crucial role in defending against herpesviruses, which is particularly relevant in paediatric [...] Read more.
Severe haematological diseases and lymphoid malignancies require bone marrow (BM)-suppressive treatments. Knowledge regarding the impact of BM-suppressive treatments on children’s memory T cells is very limited. Memory T cells play a crucial role in defending against herpesviruses, which is particularly relevant in paediatric cancer care. We studied 53 children in total; 34 with cancer and 2 with severe haematological disorders, with some receiving BM-suppressive treatment with or without allogeneic–haematopoietic stem cell transplantation (allo-HSCT), alongside 17 healthy controls. We focused on peripheral blood proportions of memory T-cell subsets using flow cytometry and analysed cytokine-secreting T cells with a four-parameter FluoroSpot assay in response to T-cell mitogen and varicella zoster virus (VZV) peptides. Patients on BM-suppressive treatment showed increased clusters of differentiation (CD)4+ and CD8+ effector memory (TEM)/terminally differentiated effector (TEFF) T cells compared to the healthy controls. They also exhibited, amongst other things, when compared to the healthy controls, a reduced total number of cytokine-secreting cells, by means of interferon (IFN)-γ, interleukin (IL)-17A, IL-10, and IL-22, following mitogen activation. A diminished IFN-γ response among the children with BM-suppressive treatment was observed upon VZV-peptide stimulation, compared to the healthy children. Collectively, the findings herein indicate that the children who are undergoing or have finished BM-suppressive treatment display qualitative differences in their T-cell memory compartment, potentially increasing their susceptibility to severe viral infections and impacting their immunotherapy, which relies on the functional ability of autologous T cells. Full article
(This article belongs to the Special Issue Advanced Research on Immune Cells and Cytokines)
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12 pages, 2484 KiB  
Article
Transplantation of Mesenchymal Stem Cells Derived from Old Rats Improves Healing and Biomechanical Properties of Vaginal Tissue Following Surgical Incision in Aged Rats
by Ofra Ben Menachem-Zidon, Benjamin Reubinoff and David Shveiky
Int. J. Mol. Sci. 2024, 25(11), 5714; https://doi.org/10.3390/ijms25115714 - 24 May 2024
Cited by 3 | Viewed by 1310
Abstract
Pelvic floor dysfunction encompasses a group of disorders that negatively affect the quality of women’s lives. These include pelvic organ prolapse (POP), urinary incontinence, and sexual dysfunction. The greatest risk factors for prolapse are increased parity and older age, with the largest group [...] Read more.
Pelvic floor dysfunction encompasses a group of disorders that negatively affect the quality of women’s lives. These include pelvic organ prolapse (POP), urinary incontinence, and sexual dysfunction. The greatest risk factors for prolapse are increased parity and older age, with the largest group requiring surgical intervention being post-menopausal women over 65. Prolapse recurrence rates following surgery were reported to be as high as 30%. This may be attributed to ineffective healing in the elderly. Autologous stem cell transplantation during surgery may improve surgical results. In our previous studies, we showed that the transplantation of bone marrow-derived mesenchymal stem cells (MSCs) from young donor rats improved the healing of full-thickness vaginal surgical incision in the vaginal wall of old rats, demonstrated by both histological and functional analysis. In order to translate these results into the clinical reality of autologous MSC transplantation in elderly women, we sought to study whether stem cells derived from old donor animals would provide the same effect. In this study, we demonstrate that MSC transplantation attenuated the inflammatory response, increased angiogenesis, and exhibited a time-dependent impact on MMP9 localization. Most importantly, transplantation improved the restoration of the biomechanical properties of the vagina, resulting in stronger healed vaginal tissue. These results may pave the way for further translational studies focusing on the potential clinical autologous adjuvant transplantation of MSCs for POP repair for the improvement of surgical outcomes. Full article
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11 pages, 790 KiB  
Article
Evaluation of the Safety and Efficacy of Repeated Mesenchymal Stem Cell Transplantations in ALS Patients by Investigating Patients’ Specific Immunological and Biochemical Biomarkers
by Zahraa Alkhazaali-Ali, Sajad Sahab-Negah, Amir Reza Boroumand, Najmeh Kaffash Farkhad, Mohammad Ali Khodadoust and Jalil Tavakol-Afshari
Diseases 2024, 12(5), 99; https://doi.org/10.3390/diseases12050099 - 12 May 2024
Cited by 1 | Viewed by 2042
Abstract
Background: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell [...] Read more.
Background: Amyotrophic lateral sclerosis (ALS) is an incurable disease. There are vigorous attempts to develop treatments to reduce the effects of this disease, and among these treatments is the transplantation of stem cells. This study aimed to retrospectively evaluate a mesenchymal stem cell (MSC) therapy cohort as a promising novel treatment modality by estimating some additional new parameters, such as immunological and biochemical factors. Methods: This study was designed as an open-label, one-arm cohort retrospective study to evaluate potential diagnostic biomarkers of repeated infusions of autologous-bone marrow-derived mesenchymal stem cells (BM-MSCs) in 15 confirmed patients with ALS, administered at a dose of 1 × 106 cells/kg BW with a one-month interval, in equal amounts in both an intravenous (IV) and intrathecal (IT) capacity simultaneously, via various biochemical (iron (Fe), ferritin, total-iron-binding capacity (TIBC), transferrin, and creatine kinase (CK)) and immunological parameters (tumor necrosis factor-alpha (TNF-α), neurofilament light chain (NFL), and glial-cell-derived neurotrophic factor (GDNF) levels, evaluated during the three-month follow-up period in serum and cerebrospinal fluid (CSF). Results: Our study indicated that, in the case of immunological biomarkers, TNF-α levels in the CSF showed a significant decrease at month three after transplantation compared with levels at month zero, and the p-value was p < 0.01. No statistically significant changes were observed for other immunological as well as biochemical parameters and a p-value of p > 0.05. Conclusions: These results can indicate the potential benefit of stem cell transfusion in patients with ALS and suggest some diagnostic biomarkers. Several studies are required to approve these results. Full article
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20 pages, 1820 KiB  
Article
Atorvastatin Treatment Significantly Increased the Concentration of Bone Marrow-Derived Mononuclear Cells and Transcutaneous Oxygen Pressure and Lowered the Pain Scale after Bone Marrow Cells Treatment in Patients with “No-Option” Critical Limb Ischaemia
by Jan Kyselovic, Adriana Adamičková, Andrea Gažová, Simona Valášková, Nikola Chomaničová, Zdenko Červenák and Juraj Madaric
Biomedicines 2024, 12(4), 922; https://doi.org/10.3390/biomedicines12040922 - 22 Apr 2024
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Abstract
Background: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with ”no-option“ critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agents pharmacotherapy [...] Read more.
Background: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with ”no-option“ critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agents pharmacotherapy related to the therapeutic efficacy of BMCs treatment. Methods: In the present study, we reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 mL of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (N = 22) were considered as responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (N = 13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression, and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors, and the risk of major amputation. Results: Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO2) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI), and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP > 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (N = 22) had significantly improved TcPO2 and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (N = 20) had significantly reduced pain scale after BMCs transplant, compared to the non-RAS-acting agents group. Similar results, reduced pain scale and improved TcPO2, were achieved in patients treated with atorvastatin and RAS-acting agents (N = 17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. Conclusions: CRP and TcPO2 were prognostic factors of the responders, while CRP value, ABI, and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO2 and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responders and previous treatment before BMCs transplant with RAS-acting agents alone or with atorvastatin were significant. Full article
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7 pages, 661 KiB  
Brief Report
The Dark Side of Activated Phosphoinositide 3-Kinase-δ Syndrome 2: A Story Rewritten through FDG-PET
by Arianna Catelli, Cristina Nanni, Rita Mulè, Pier Luigi Zinzani, Elena Sabattini, Marcello Lanari and Francesca Conti
J. Clin. Med. 2024, 13(8), 2203; https://doi.org/10.3390/jcm13082203 - 11 Apr 2024
Cited by 1 | Viewed by 1425
Abstract
Background: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is characterized by lymphoproliferation and increased risk of malignancy. FDG-PET/CT may represent a helpful diagnostic tool for differentiating these clinical features and correctly diagnosing inborn errors of immunity (IEI). Case report: We present the case of [...] Read more.
Background: Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is characterized by lymphoproliferation and increased risk of malignancy. FDG-PET/CT may represent a helpful diagnostic tool for differentiating these clinical features and correctly diagnosing inborn errors of immunity (IEI). Case report: We present the case of a female patient diagnosed with Hodgkin’s lymphoma at 19 years of age, although atypical imaging aspects emerged: baseline FDG-PET/CT revealed several hot lymph nodes with a symmetrical distribution, and increased tracer uptake in spleen, axial, and appendicular bone marrow. Imaging repeated after chemotherapy and autologous stem cell transplantation showed persistent increased FDG uptake at multiple supradiaphragmatic nodes and in bone marrow. After the diagnosis of APDS2 and rapamycin treatment, FDG-PET/CT confirmed complete metabolic normalization of all sites. Conclusions: In the IEI scenario, FDG-PET/CT plays an effective role in differentiating malignant proliferation and immune dysregulation phenotypes. Atypical patterns at FDG-PET/CT should be interpreted as a red flag for the need of an early immunological evaluation. Full article
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