Cytotherapy最新文献

{"title":"Safety and efficacy of adipose-derived mesenchymal stem cell therapy in elderly Parkinson's disease patients: an intermediate-size expanded access program","authors":"Ridhima Vij ,&nbsp;Hosu Kim ,&nbsp;Hyeonggeun Park ,&nbsp;Thanh Cheng ,&nbsp;Djamchid Lotfi ,&nbsp;Donna Chang","doi":"10.1016/j.jcyt.2024.09.004","DOIUrl":"10.1016/j.jcyt.2024.09.004","url":null,"abstract":"<div><h3>Objective</h3><div>This intermediate-size expanded access program aimed to evaluate safety and clinical efficacy of multiple intravenous infusions of autologous, Hope Biosciences adipose-derived mesenchymal stem cell (HB-adMSC) therapy in elderly patients with Parkinson's disease (PD).</div></div><div><h3>Methods</h3><div>Ten eligible participants (aged 76–95 years) received six intravenous infusions each with 200MM autologous HB-adMSCs over 18 weeks, with the end of study (EOS) at week 26. Safety was assessed through adverse events (AEs) and serious adverse events (SAEs). Efficacy was measured through improvements in both motor and non-motor symptoms, utilizing scales including Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I-IV, Parkinson's Disease Questionnaire-39 (PDQ-39), Parkinson's disease Fatigue Scale (PFS-16), Patient Health Questionnaire-9 (PHQ-9), and Visual Analog Scale (VAS). Analysis employed paired t-tests and Minimal Clinically Important Difference (MCID) thresholds for the patient-reported outcomes.</div></div><div><h3>Results</h3><div>Most AEs (37 out of 46) were mild in severity, with 5 SAEs reported, none attributed to the drug. No deaths occurred. Despite lack of statistical significance across the efficacy endpoints, modest yet clinically meaningful improvements with effect size &gt; 0.3 were observed in several secondary efficacy endpoints (MDS-UPDRS part I &amp; III, PDQ-39, and PHQ-9) at the EOS, nearing or surpassing the established MCID values.</div></div><div><h3>Conclusions</h3><div>The administration of autologous 200MM HB-adMSCs was found to be safe and well-tolerated in the elderly PD population. Although not achieving statistical significance, modest clinical improvements were noted across multiple secondary endpoints. These findings underscore the safety profile of the treatment in elderly patients and highlight the importance of evaluating clinical relevance alongside statistical measures for meaningful patient outcomes. Further investigation with a larger, randomized, placebo-controlled design is warranted to validate these observations.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 181-187"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of a single dose of cryopreserved human umbilical cord mesenchymal stromal cells for the treatment of knee osteoarthritis:a randomized, controlled, double-blind pilot study","authors":"Omar Amado Pico ,&nbsp;Francisco Espinoza ,&nbsp;María Ignacia Cádiz ,&nbsp;Claudia L. Sossa ,&nbsp;Silvia M. Becerra-Bayona ,&nbsp;María C. Canencio Salgado ,&nbsp;Javier Eduardo Rengifo Rodríguez ,&nbsp;Oscar Fabian Valdivieso Cárdenas ,&nbsp;Johanna Marcela Quintero Cure ,&nbsp;Maroun Khoury ,&nbsp;Martha L. Arango-Rodríguez","doi":"10.1016/j.jcyt.2024.09.005","DOIUrl":"10.1016/j.jcyt.2024.09.005","url":null,"abstract":"<div><h3>Background</h3><div>Knee osteoarthritis (OA) is the most prevalent degenerative musculoskeletal disorder, which is particularly common in older population. While conventional treatments have limited effectiveness, the development of more effective therapeutic strategies is necessary to address this primary source of pain and disability. Umbilical cord mesenchymal stromal cells (UC-MSCs) offer a promising therapeutic approach for treating knee OA.</div></div><div><h3>Aim</h3><div>This randomized, prospective, double-blind and controlled pilot study was carried out to evaluate and compare the safety and therapeutic efficacy of a single intra-articular injection of a standardized product CellistemOA (5 × 10⁶ ± 5 × 10⁵ UC-MSCs), vs. triamcinolone (a synthetic corticosteroid) (10 mg/mL) in thirty patients with symptomatic knee OA (Kellgren–Lawrence grade II or III).</div></div><div><h3>Methods</h3><div>The outcomes included changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores based on a Likert scale, numerical rating score (NRS) for pain, Magnetic Resonance Imaging (MRI), and quality of life (SF-36 questionnaire), from baseline and throughout 12-months of follow-up.</div></div><div><h3>Results</h3><div>Patients treated with CellistemOA showed significant improvement in WOMAC score (including the three subscale scores (pain, stiffness and function), NRS in pain, and SF-36 profile from baseline to 12 months (<em>p</em> &lt; 0.05) compared to the triamcinolone group, and no severe adverse events were reported. There were no significant differences in MRI WORMS scores between the two groups. However, patients who received the cellular treatment experienced a significant improvement in their SF-36 profile (<em>p</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>This pilot study revealed that a single dose of CellistemOA is safe and superior to the active comparator in knee OA at 1-year of follow-up, making it a compelling therapeutic alternative to treat symptomatic OA patients.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 188-200"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcome of donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation in relapsed myelodysplastic syndrome","authors":"Atsushi Marumo ,&nbsp;Yasunobu Nagata ,&nbsp;Machiko Fujioka ,&nbsp;Shuhei Kurosawa ,&nbsp;Yuho Najima ,&nbsp;Emiko Sakaida ,&nbsp;Noriko Doki ,&nbsp;Kentaro Fukushima ,&nbsp;Shuichi Ota ,&nbsp;Katsuhiro Shono ,&nbsp;Ayumu Ito ,&nbsp;Naoyuki Uchida ,&nbsp;Tetsuya Nishida ,&nbsp;Masashi Sawa ,&nbsp;Hiroko Tsunemine ,&nbsp;Ken-ichi Matsuoka ,&nbsp;Onizuka Makoto ,&nbsp;Yoshinobu Kanda ,&nbsp;Takahiro Fukuda ,&nbsp;Yoshiko Atsuta ,&nbsp;Hidehiro Itonaga","doi":"10.1016/j.jcyt.2024.09.006","DOIUrl":"10.1016/j.jcyt.2024.09.006","url":null,"abstract":"<div><h3>Background aims</h3><div>Allogeneic hematopoietic stem cell transplantation (HSCT) improves outcomes for myelodysplastic syndrome (MDS) patients, but relapse rates remain high, and postrelapse treatment options are limited. Therefore, this study aimed to identify the factors contributing to the response to donor lymphocyte infusion (DLI) in relapsed MDS patients post-HSCT.</div></div><div><h3>Methods</h3><div>This study included 107 patients with relapsed and DLI-treated MDS who underwent their first HSCT between 2002 and 2022 and were registered in the Transplant Registry Unified Program. Univariate and multivariate survival analyses were conducted using log-rank tests and Cox proportional hazards models. Overall survival (OS) and response rates to DLI were also analyzed.</div></div><div><h3>Results</h3><div>The 1-year OS was 30.0% and univariate analysis identified poor prognostic factors: age ≥58 years (<em>P</em> = 0.003), complex karyotype (<em>P</em> = 0.026), hematologic relapse (<em>P</em> = 0.026) and early relapse (<em>P</em> = 0.004). Azacitidine plus DLI also improved prognosis (<em>P</em> &lt; 0.001). Multivariate analysis confirmed age ≥58 years, hematologic relapse, and early relapse as poor prognostic factors. The adjusted OS for patients aged ≥58 years who relapsed &lt;110 days post-transplant showed that the 1-year OS in patients with cytogenetic/molecular relapse was 43.6%, compared to 9.4% for those with hematologic relapse. Acute graft-versus-host disease (GVHD) occurred in 62.3% of patients, and chronic GVHD in 30.8%, with manageable outcomes.</div></div><div><h3>Conclusions</h3><div>DLI may improve OS in younger patients, those with cytogenetic/molecular relapse, and those with late relapse. Despite the risk of GVHD, its impact on prognosis is minimal. Given the limited treatment options, DLI should be considered for relapsed MDS patients post-HSCT.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 2","pages":"Pages 222-228"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation in the osmotic characteristics of aging red blood cells: insights for cryopreservation optimization.","authors":"Sanaz Hemmatibardehshahi, Mackenzie Brandon-Coatham, Andrew Holt, Jason P Acker","doi":"10.1016/j.jcyt.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.01.010","url":null,"abstract":"<p><p>Cryopreservation is a long-term storage strategy for maintaining the quality of red blood cells (RBCs) used for clinical and industrial purposes. However, cryopreservation can induce osmotic stress, leading to a 15 to 20% loss of RBCs during freezing/thawing and cryoprotectant addition/removal. This study investigated how the biological aging of RBCs influences their osmotic characteristics. We hypothesized that biologically older RBCs (O-RBCs) would exhibit diminished osmotic features compared to biologically younger RBCs (Y-RBCs), thereby contributing to their loss during cryopreservation. Seven red cell concentrates (RCCs) were pooled, and their density profile was determined using Percoll separation. Y-RBCs and O-RBCs, representing the extremes of the density spectrum, were isolated. Rheological parameters (O_hyper, EI_max, EI_hyper, K_EI) were measured with laser ektacytometry. Osmotic fragility and hemolysis tests were performed to assess subpopulation responses to osmotic stress. Water (L_p) and solute permeability (P_s) of these subpopulations, in addition to unseparated RBCs (U-RBCs), were measured using stopped-flow spectroscopy. Aliquots of Y- and O-RBCs were differentially labeled with biotin and spiked back into a pooled unit. The pooled unit was split into five, and cryopreserved via a high glycerol/slow-cooling method, a standard method adopted by international blood banks. Glycerolization and deglycerolization were conducted using the Haemonetics ACP 215 Automated Cell Processor. Flow cytometry was used to assess the recovery of biotinylated RBCs (BioRBCs) before glycerolization and following post-thaw deglycerolization on days 1 and 14. O-RBCs exhibited the highest rigidity (K_EI) and lowest O_hyper, EI_max, and EI_hyper. Osmotic hemolysis and osmotic fragility indicated that O-RBCs exhibited superior tolerance to hypotonic solutions than Y- and U-RBCs (P < 0.05). O-RBCs demonstrated significantly higher L_p values than Y-RBCs across hypo- and hypertonic conditions (P < 0.05). O-RBCs had the highest P_s during deglycerolization (P < 0.05). Y- and O-BioRBCs showed a stable trend throughout the 14 days of hypothermic storage (1-4°C) post-deglycerolization, with no significant difference between subpopulations. The study revealed that biological aging is associated with alterations in the osmotic and rheological properties of RBCs. Despite notable differences in osmotic characteristics, under the test conditions, survival rates of Y- and O-BioRBCs remained comparable after 14 days of hypothermic storage. These findings potentially support that tailoring cryopreservation protocols to specific RBC subpopulations can improve recovery rates and make cryopreservation more clinically efficient and broadly applicable.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fellowship training for cellular therapy laboratory directors.","authors":"Ashley A Krull, Margaret A DiGuardo, Michael C Deeds, Christel A Skaer, Kathleen A Soiney, Michelle Wadewitz, Timothy D Wiltshire, Dennis A Gastineau, Allan B Dietz, Eapen K Jacob","doi":"10.1016/j.jcyt.2025.01.013","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.01.013","url":null,"abstract":"<p><p>The rapidly evolving field of cell and gene therapy (CGT) demands a new generation of leaders capable of managing complex manufacturing processes while navigating stringent regulatory environments. To address this need, Mayo Clinic established a Cellular Therapy Fellowship (CTF) program specifically designed to train future laboratory directors by integrating hands-on manufacturing experience with didactic instruction in laboratory management, quality systems, and regulatory science. The CTF curriculum includes structured rotations through cleanroom manufacturing, quality assurance, and process development groups. Fellows gain expertise in diverse manufacturing platforms, such as CAR-T cells, mesenchymal stromal cells, and other cellular therapies, while overseeing manufacturing for clinical trials and product development. Once competent, fellows transition into an Acting Director role, wherein fellows make real-time decisions under supervision, preparing them for the responsibilities of independent leadership. Since its inception, the program has trained fellows with diverse backgrounds, including PhD- and MD-trained professionals, tailoring their experiences to career goals. Graduates demonstrate competencies in laboratory management, cGMP manufacturing, and translational research through notable deliverables such as publications, conference presentations, and regulatory submissions. This manuscript outlines the development, implementation, and outcomes of the program, providing a roadmap for institutions to establish their own fellowship programs and cultivate the next generation of CGT laboratory leaders.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probing mechanisms of cryopreservation damage to natural killer cells.","authors":"Adam Joules, Akshat S Mallya, Troy Louwagie, Guanglin Yu, Allison Hubel","doi":"10.1016/j.jcyt.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.01.012","url":null,"abstract":"<p><strong>Background aims: </strong>Natural killer (NK) cells show significant potential in targeting hard to treat cancers, but these cells need effective preservation methods to maintain viability and efficacy after cryopreservation. Traditional methods of preserving NK cells result in low post-thaw recovery and function. Dimethyl sulfoxide (DMSO) is a very common cryoprotectant for preserving NK cells, but its infusion into patients post-thaw can cause dose-dependent adverse effects, including nausea, discomfort and cardiac arrest. The aim of this work was to evaluate low DMSO- and osmolyte-based cryopreservation solutions across multiple steps in the cryopreservation process for NK cells.</p><p><strong>Methods: </strong>This study investigated NK cell membrane responses to cryoprotectants, dependence of cell survival on cooling rate and nucleation temperature and influence of osmotic shock and pH changes with regard to freezing NK cells using the NK cell line NK-92 as a model system.</p><p><strong>Results: </strong>Exposure to cryoprotectants reduced the membrane fluidity and NK cell-induced cytotoxicity of the cells before freezing, but combinations of osmolytes mitigated this loss. The introduction of cryoprotectants did not reduce perforin or granzyme content, and slow or rapid dilution after thawing did not reduce viability, recovery or proliferation. Controlled rate freezing and Raman cryomicroscopy studies revealed that NK cells tolerated fast cooling rates, and the optimal cooling rate for NK cells was 4-5°C/min. Raman cryomicroscopy mapped the distribution of cryoprotectants and ice of frozen NK cells at -50°C, showing a reduction in cytotoxic granule signal.</p><p><strong>Conclusions: </strong>The large, osmotically inactive volume of NK cells demonstrates cell sensitivity to cryoprotectants and freezing. Exposure to cryoprotectants can reduce NK cell-induced cytotoxicity and membrane fluidity. We hypothesize that cell dehydration and freezing disrupt cytolytic granules, causing NK intracellular damage. These data emphasize the importance of developing robust techniques to enhance the cryopreservation of NK cells and indicate the points where cell damage occurs.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical impact of donor telomere length after umbilical cord blood transplantation.","authors":"Kazuki Nagao, Megumi Watanuki, Hidenori Hayashi, Natsuki Kawamata, Kai Kuroiwa, Hinako Narita, Reiko Okamura, Shotaro Shimada, Nana Arai, Yukiko Kawaguchi, Kouji Yanagisawa, Norimichi Hattori","doi":"10.1016/j.jcyt.2025.01.011","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.01.011","url":null,"abstract":"<p><strong>Background and aims: </strong>Several studies have shown that the telomere length of engrafted donor cells affects the clinical outcomes in patients with hematologic diseases after allogeneic stem-cell transplantation (allo-SCT). However, the relationship between donor telomere length and clinical outcomes after umbilical-cord blood transplantation (UCBT) remains unknown. The study aim was to assess the relationship between donor telomere length and transplantation outcomes.</p><p><strong>Methods: </strong>We measured donor-derived relative telomere length (RTL) in 75 patients after single-unit UCBT and evaluated the association between telomere length and transplantation outcomes.</p><p><strong>Results: </strong>Compared with patients with shorter RTL, patients with longer RTL had a higher risk of bacterial and bloodstream infections [hazard ratio (HR), 4.79; 95% confidence interval (CI), 1.70-13.46; P = 0.003 and HR, 3.43; 95% CI, 1.19-9.82; P = 0.022, respectively] and was possibly associated with reduced relapse (HR 0.44, 95% CI 0.15-1.27, P = 0.13) by multivariate analysis.</p><p><strong>Conclusions: </strong>Patients after UCBT who received engrafted donor cells with longer RTL had a higher risk of bacterial and bloodstream infections. The measured donor-derived RTL at engraftment after UCBT may predict clinical outcomes.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sickle cell disease gene therapy drug expenses and reimbursement: a litmus test for commercial pricing strategy and patient access for curative therapies.","authors":"Bambi J Grilley, Ashley Hume, Jacques Galipeau","doi":"10.1016/j.jcyt.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.01.008","url":null,"abstract":"<p><p>Durable gene therapies newly approved by the Food and Drug Administration for sickle cell disease offer the promise of cure with subsequent improvement in quality of life through avoidance of repeated hospitalizations and worsening of disabilities in these patients. In the United States, following Food and Drug Administration approval, lovotibeglogene autotemcel (Lyfgenia, bluebird bio, Inc, Sommerville, MA, USA) and exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals Inc, Boston, MA, USA) were launched in 2024 for treatment of patients 12 years and older with frequent vaso-occlusive crises. Here we will discuss the first treatment with lovotibeglogene as a test case serving to highlight the multiple drug reimbursement pathways in the United States for cell and gene products for orphan disorders and their impact on patient adoption and access.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A phase 1, open-label study to determine safety and tolerability of the topical application of mesenchymal stem/stromal cell (MSC) exosome ointment to treat psoriasis in healthy volunteers.","authors":"Nisha Suyien Chandran, Monil Nagad Bhupendrabhai, Thong Teck Tan, Bin Zhang, Sai Kiang Lim, Andre Boon Hwa Choo, Ruenn Chai Lai","doi":"10.1016/j.jcyt.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.jcyt.2025.01.007","url":null,"abstract":"<p><strong>Background: </strong>Topical application of mesenchymal stem/stromal cell (MSC) exosomes have yielded encouraging results in the treatment of psoriasis in pre-clinical studies. The safety of topical applications of MSC exosome in ointment has not yet been determined in human subjects.</p><p><strong>Objective: </strong>To assess the safety and tolerability of an MSC exosome ointment, PTD2021P, for topical application in healthy adult volunteers.</p><p><strong>Methods: </strong>Ten healthy adult volunteers were enrolled. All subjects received topical treatment with PTD2021P immediately followed by Vesiderm liposome cream ter in die (TID) (thrice a day) on the forearm with a gap of 4 hours between doses for 20 days and underwent another round of screening procedure at end of study (Day 21 + 3 days). Screening procedures included vital signs, blood examinations, photographs and visual assessment of the area of application. All through the treatment period, the subjects completed the daily Subject Diary to capture adverse events, concomitant medications, and time of study product application.</p><p><strong>Results: </strong>One subject was reported with 1 treatment-emergent adverse event (TEAE) of COVID-19 infection during the study. The TEAE was moderate in severity and unlikely related to the study drug. This TEAE was resolved and the subject recovered fully. No subject was reported with clinically significant abnormality for laboratory parameters. As per the visual assessment of the area of application, no subject had dryness, itch, oozing/crusting, redness, scratch marks, skin thickening, sleeplessness, or swelling at the area of application of skin.</p><p><strong>Conclusions: </strong>PTD 2021P was well tolerated for topical application. There were no serious adverse events (SAEs) or TEAEs related to the treatment, and no subject discontinued the study. No clinically significant abnormality was reported for laboratory parameters and vital signs. No abnormality was reported for visual assessment of the area of application of exosome ointment. This ointment could be an alternative therapeutic option for patients who are refractory to current first line therapy.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparison of mobilization regimens used in Hodgkin lymphoma and factors that influence peripheral blood stem cell mobilization.","authors":"Anant Gokarn, Laxma Reddy, Sumathi Hiregoudar, Minal Poojary, Sarika Parab, Sachin Punatar, Akanksha Chichra, Sumeet Mirgh, Nishant Jindal, Lingaraj Nayak, Keshav Garg, Suryatapa Saha, Shashank Ojha, Prashant Tembhare, Sweta Rajpal, Gaurav Chatterjee, Nikhil Patkar, Sadhana Kannan, Akash Pawar, Bhausaheb Bagal, Papagudi Ganesan Subramanian, Navin Khattry","doi":"10.1016/j.jcyt.2025.01.004","DOIUrl":"10.1016/j.jcyt.2025.01.004","url":null,"abstract":"<p><strong>Background: </strong>Various chemotherapy regimens have been used for chemo-mobilization of stem cells prior to autologous stem cell transplant in patients with Hodgkin lymphoma, and there is no clear standard of care. In this retrospective study, we analyzed mobilization outcomes and the factors affecting successful mobilization following different salvage chemotherapy regimens used in Hodgkin lymphoma.</p><p><strong>Objectives: </strong>The primary objective was to compare success rates of different chemotherapy regimens. Successful mobilization was defined as the ability to harvest at least 2 × 10⁶/kg of stem cells during one mobilization attempt. Secondary objectives were to find factors that influenced mobilization failures.</p><p><strong>Study design and methods: </strong>This is a single-center, retrospective analysis of all Hodgkin lymphoma patients for whom peripheral blood stem cell (PBSC) mobilization was attempted at Tata Memorial Centre, Mumbai, India between December 1, 2007, and June 30, 2022. Salvage chemotherapy that was being used to treat relapsed/refractory lymphoma was generally preferred as a chemo-mobilization regimen. For patients who had already completed all salvage-chemotherapy cycles, GCSF ± plerixafor was used. Clinical parameters (age, sex, stage, lines of treatment, use of radiation therapy, disease status at time of harvest, platelet count at relapse) and stem cell collection parameters (day of chemotherapy, peripheral blood CD34 cell count on D1 of harvest, number of days of harvest, CD34 cells collected on D1 and total CD34 cells collected) were extracted from medical records and analyzed.</p><p><strong>Results: </strong>A total of 174 PBSC mobilization attempts were made in 169 Hodgkin lymphoma patients during the study period. Chemo-mobilization with gemcitabine-dexamethasone-platinum (GDP)- and cytarabine-based regimens led to successful harvests in 95% and 100% patients, respectively. GDP-based mobilization was significantly better than other regimens and granulocyte colony-stimulating factor (G-CSF) (±plerixafor) mobilization (82%) (P = 0.000082). Patients who had previous radiation exposure to mediastinum, spine or pelvis and underwent mobilization following ifosfamide-based mobilization had a mobilization failure rate of 37%.</p><p><strong>Conclusions: </strong>GDP and cytarabine-based regimen have better mobilization success compared to ifosfamide-based regimen or G-CSF (±plerixafor) in lymphoma patients. It may be best to avoid ifosfamide-based regimens in patients who have received radiation to mediastinum, spine or pelvis due to high rates of mobilization failure.</p>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}