Cytotherapy最新文献

{"title":"Efficacy of chimeric antigen receptor engineered natural killer cells in the treatment of hematologic malignancies: a systematic review and meta-analysis of preclinical studies","authors":"Donald J. Bastin ,&nbsp;Marisa K. Kilgour ,&nbsp;Risa Shorr ,&nbsp;Elham Sabri ,&nbsp;Aurélien Delluc ,&nbsp;Michele Ardolino ,&nbsp;Scott McComb ,&nbsp;Seung-Hwan Lee ,&nbsp;David Allan ,&nbsp;Tim Ramsay ,&nbsp;Alissa Visram","doi":"10.1016/j.jcyt.2024.11.004","DOIUrl":"10.1016/j.jcyt.2024.11.004","url":null,"abstract":"<div><h3>Background</h3><div>Chimeric antigen receptor (CAR) engineered NK cells (CAR-NK) are a novel approach to the immunotherapy of hematologic malignancies which seeks to overcome some of the challenges faced by CAR-T cells (CAR-T). With few published clinical studies, preclinical studies can identify strategies to accelerate clinical translation. We conducted a systematic review on the preclinical <em>in vivo</em> use of CAR-NK for the treatment of hematologic malignancies to assess these therapies in a holistic and unbiased manner.</div></div><div><h3>Methods</h3><div>Our protocol was registered with PROSPERO (ID: CRD42023438375). We performed a search of OVID MEDLINE, OVID Embase, and Embase for animal studies employing human CAR-NK cells in the treatment of hematologic malignancies. Screening of studies for eligibility criteria was performed in duplicate. Our primary outcomes were survival and reduction in tumor volume<em>.</em> Data extraction from individual experiments was performed by one reviewer using Digitizeit^TM software and verified by a second reviewer. Meta-analysis and subgroup analyses were performed using Comprehensive Meta-Analysis^TM software. Information for descriptive outcomes was extracted in duplicate by two independent reviewers. Risk of bias was assessed using the SYRCLE Risk of Bias Tool for Animal Studies.</div></div><div><h3>Results</h3><div>A total of 34 papers met eligibility criteria. Overall, CD19 was the most common antigen targeted however there was substantial diversity in antigenic targets, source material for generating CAR-NK cells, and NK cell modifications. Mice treated with CAR-NK therapy survived significantly longer than untreated mice (median survival ratio of 1.18, 95% CI: 1.10–1.27, <em>P</em> &lt; 0.001), and mice treated with nonengineered NK cells (median survival ratio 1.13, 95% CI: 1.03–1.23, <em>P</em> &lt; 0.001). Similarly, treatment with CAR-NK significantly reduced the tumor burden when compared to untreated mice (ratio of mean tumor volume 0.23, 95% CI: 0.17–0.32, <em>P</em> &lt; 0.001) or mice treated with nonengineered NK cells (ratio of mean tumor volume 0.37, 95% CI: 0.28–0.51, <em>P</em> &lt; 0.001). Subgroup analysis showed that cotreatment with IL-15 reduced tumor volume but did not increase survival. In general, CAR-NK cell persistence was short but was increased by IL-15.</div></div><div><h3>Conclusions</h3><div>CAR-NK shows promise for the treatment of hematologic malignancies in preclinical models.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 350-364"},"PeriodicalIF":3.7,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848214","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":"Role of mesenchymal stromal cell secretome on recovery from cellular senescence: an overview","authors":"Karynne de Nazaré Lins de Brito ,&nbsp;Andréa Gonçalves Trentin","doi":"10.1016/j.jcyt.2024.11.014","DOIUrl":"10.1016/j.jcyt.2024.11.014","url":null,"abstract":"<div><div>Cellular senescence is intricately linked with numerous changes observed in the aging process, including the depletion of the stem cell pool and the decline in tissue and organ functions. Over the past three decades, efforts to halt and reverse aging have intensified, bringing rejuvenation closer to reality. Current strategies involve treatments using stem cells or their derivatives, such as the secretome. This article aims to highlight key points and evaluate the utilization of secretome derived from mesenchymal stromal cells (MSCs) as an antisenescent approach. Employing a quasi-systematic research approach, the authors conducted a comprehensive analysis based on a search algorithm targeting the <em>in vitro</em> effects of MSC-derived secretome on rescuing cells from a senescent state. Reviewing 39 articles out of 687 hits retrieved from PubMed and Scopus without a time limit, the authors synthesized information and identified common types of MSC-tissue sources utilized (including bone marrow-MSCs, umbilical cord-MSCs, iPSC-derived MSCs, adipose tissue-MSCs, dental pulp-MSCs, amniotic membrane-MSCs, placenta-MSCs, gingival-MSCs, urine-MSCs, and commercially available MSC lineages) from both human and other species (such as mice and rats). The authors also examined the forms of secretome tested (including conditioned media and extracellular vesicles), the cell types treated (MSCs or other cell types), methods/biomarkers of monitoring senescence/rejuvenation, and the mechanisms involved. Ultimately, this review underscores the proof-of-principle of the beneficial effects of MSC-derived secretome in reversing cellular senescence across various cell types. Such insights might aid the scientific community in designing improved <em>in vitro</em> and <em>in vivo</em> assays for future research and clinical validation of this promising cell-free therapy.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 4","pages":"Pages 422-437"},"PeriodicalIF":3.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829973","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":"Efficient manufacturing of CAR-T cells from whole blood: a scalable approach to reduce costs and enhance accessibility in cancer therapy","authors":"Roshini Traynor ,&nbsp;Isabella Vignola ,&nbsp;Sarmila Sarkar ,&nbsp;Michaela Prochazkova ,&nbsp;Yihua Cai ,&nbsp;Rongye Shi ,&nbsp;Sarah Underwood ,&nbsp;Supriya Ramanujam ,&nbsp;Bonnie Yates ,&nbsp;Sara Silbert ,&nbsp;Ping Jin ,&nbsp;Alexandra Dreyzin ,&nbsp;Nirali N. Shah ,&nbsp;Robert P. Somerville ,&nbsp;David F. Stroncek ,&nbsp;Hannah W. Song ,&nbsp;Steven L. Highfill","doi":"10.1016/j.jcyt.2024.11.013","DOIUrl":"10.1016/j.jcyt.2024.11.013","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chimeric antigen receptor T (CAR-T) cells have significantly advanced the treatment of cancers such as leukemia and lymphoma. Traditionally, T cells are collected from patients through leukapheresis, an expensive and potentially invasive process that requires specialized equipment and trained personnel. Although whole blood collections are much more technically straightforward, whole blood starting material has not been widely utilized for clinical CAR-T cell manufacturing, in part due to lack of manufacturing processes designed for use in a good manufacturing practice (GMP) environment. Collecting cellular starting material from whole blood without leukapheresis could reduce manufacturing complexity and cost, thereby improving accessibility to CAR-T cell therapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Whole blood samples were collected from eight healthy donors and one pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient. These samples were processed using the Sepax C-Pro (Cytiva) instrument to isolate mononuclear cells (MNCs) via density gradient separation. CAR-T cells were then manufactured from the isolated MNCs using a GMP-compliant 7-day protocol, whereby T cells were activated with anti-CD3 and IL-2, transduced with GMP lentiviral vector encoding a CD19/CD22 bispecific CAR, and expanded in gas permeable cell culture bags. The resulting CAR-T cells were then evaluated for their phenotypic and functional properties using flow cytometry, cytokine release and cytotoxicity assays.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;From an average 77.7 mL of whole blood from healthy donors (range = 29–96 mL), we isolated an average of 42.2 × 10&lt;sup&gt;6&lt;/sup&gt; CD3⁺ T cells (range 7.3–63.0) postprocessing. CAR-T cell cultures were initiated from thaw using 1–10 × 10&lt;sup&gt;6&lt;/sup&gt; starting CD3&lt;sup&gt;+&lt;/sup&gt; T cells, yielding a median T cell number of 105 × 10&lt;sup&gt;6&lt;/sup&gt; cells on day 7 (range 61–188 × 10&lt;sup&gt;6&lt;/sup&gt;). We observed 66 ± 11% mean transduction efficiency and produced a mean of 77.4 × 10&lt;sup&gt;6&lt;/sup&gt; transduced CAR-T cells (range 30.8–143.5 × 10&lt;sup&gt;6&lt;/sup&gt;). Similar results were obtained when using a blood sample (28mL) obtained from a patient with relapsed B-ALL who had received recent chemotherapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Therapeutically relevant doses of CD19/CD22 CAR-T cells can be successfully manufactured from whole blood. On average, 80 mL of whole blood yields enough CAR-T cells to create a single dose for a pediatric patient (50 kg) at a dosage of 1 × 10&lt;sup&gt;6&lt;/sup&gt; CAR-T cells/kg. For larger patients, scaling up is straightforward by collecting a larger blood volume. This method also demonstrates a cost-effective approach to T cell activation and expansion which, alongside a more straightforward collection of whole blood, makes it more widely accessible especially for middle- and low-income countries. By reducing costs and labor, this strategy has the potential to significantly expand global ac","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 400-409"},"PeriodicalIF":3.7,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802984","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":"FTY720P-treated macrophages in PEG-4MAL hydrogels promote oral wound healing","authors":"Andre J. Burnham ,&nbsp;Afra I. Toma ,&nbsp;Daniel Shah ,&nbsp;Tim Cha ,&nbsp;Sundus Kaimari ,&nbsp;Monica Behara ,&nbsp;Keerthi Priya Chinniampalayam Sekar ,&nbsp;Archana Kamalakar ,&nbsp;Nick Willett ,&nbsp;Edward Botchwey ,&nbsp;Steven L. Goudy","doi":"10.1016/j.jcyt.2024.11.002","DOIUrl":"10.1016/j.jcyt.2024.11.002","url":null,"abstract":"<div><h3>Background aims</h3><div>Oral wound healing involves hemostasis, inflammation, proliferation and tissue remodeling. The oral cavity is a complex wound healing environment because of the presence of saliva, a high bacterial burden and ongoing physical trauma from eating. The inflammatory component of wound healing balances the polarization of macrophages in healing tissues between M1 inflammatory macrophages and M2 anti-inflammatory macrophages. M2 macrophages secrete anti-inflammatory and pro-regenerative cytokines and chemokines, which aid wound healing. Fingolimod, or FTY720, a Food and Drug Administration–approved sphingosine-1-phosphate modulator, has been implicated in inducing the polarization of macrophages to the M2 phenotype. In this study, we investigated whether macrophage pre-treatment with phosphorylated FTY720 (FTY720P), the bioactive form of the drug, in a PEG-4MAL hydrogel promotes improved oral wound healing in a critically sized oral mucosal defect model.</div></div><div><h3>Methods and Results</h3><div>Using cytokine dot blots and Luminex cytokine assays (MilliporeSigma, Burlington, MA, USA), FTY720P-treated murine RAW 264.7 and human THP1-differentiated macrophages in PEG-4MAL hydrogels secreted chemokines and cytokines known to regulate inflammation (e.g., interleukin [IL] 4, IL-13) and induce M2 macrophage polarization (e.g., CCL6, CCL22), leukocyte migration (e.g., CXCL2, CCL2, CCL12, CCL22), angiogenesis (e.g., vascular endothelial growth factor) and epithelialization (e.g., IL-1, IL-17, IL-22). <em>In vitro</em>, FTY720P-treated cells induced chemotaxis of macrophages and fibroblasts in Transwell assays (Corning, Corning, NY, USA) and oral epithelial scratch wound closure. In a murine oronasal fistula (ONF) model of oral wound healing, the local application of FTY720P-treated macrophages in PEG-4MAL hydrogels significantly increased wound closure (75% closure) relative to non-treated cells (40% closure) and blank hydrogel controls (25% closure) (<em>P</em> &lt; 0.0001). Flow cytometry of mouse palatal tissue showed that application of FTY720P-treated macrophage hydrogels to ONFs significantly increased day 7 percentage of M1 and M2 macrophages, mesenchymal stromal cells and CD19+ B cells. Significantly fewer neutrophils, monocytes, CD4+/CD8+ T cells and endothelial cells were observed in the FTY720P-treated macrophage defects, suggesting that FTY720P-treated macrophages in hydrogels promote oral wound healing via suppression of granulation and resolution of inflammation and promotion of tissue maturation.</div></div><div><h3>Conclusions</h3><div>Our data provide new insights into the use of potential FTY720P-treated macrophage therapies for oral wound healing and have clinical implications for cleft palate and oral surgery.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 338-349"},"PeriodicalIF":3.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814626","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":"Beyond precision: evaluation of off-target clustered regularly interspaced short palindromic repeats/Cas9–mediated genome editing","authors":"Irene Peña-Gutiérrez ,&nbsp;Beatriz Olalla-Sastre ,&nbsp;Paula Río ,&nbsp;Juan R. Rodríguez-Madoz","doi":"10.1016/j.jcyt.2024.10.010","DOIUrl":"10.1016/j.jcyt.2024.10.010","url":null,"abstract":"<div><div>The gene editing field has advanced rapidly since the development of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system because of its applicability in precisely modifying the genome. Among its multiple applications, the correction of genetic diseases has emerged as a potential curative treatment for many disorders that have eluded a cure to date. Despite its efficiency in achieving therapeutic levels of correction, the unexpected adverse effects of editing due to CRISPR/Cas9 nuclease activity are a major concern when translating these new strategies to the clinic. Multiple <em>in silico</em> tools and empirical methods have been developed to evaluate these off-target edits as well as other adverse alterations of the genome, including rearrangements, not only in <em>ex vivo</em> experiments but also in <em>in vivo</em> experiments. In this review, we summarize the available methods for the assessment of off-target effects of CRISPR/Cas9 systems, highlighting their advantages and limitations. Special attention will be paid to their application in pre-clinical studies and clinical trials, both in the manufacturing product and in the long-term follow-up of patients.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 279-286"},"PeriodicalIF":3.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802972","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":"Targeted animal models for preclinical assessment of cellular and gene therapies in pancreatic and liver diseases: regulatory and practical insights","authors":"Hongjun Wang ,&nbsp;Rachele Ciccocioppo ,&nbsp;Shuji Terai ,&nbsp;Sara Shoeibi ,&nbsp;Gianluca Carnevale ,&nbsp;Giulia De Marchi ,&nbsp;Atsunori Tsuchiya ,&nbsp;Soichi Ishii ,&nbsp;Takafumi Tonouchi ,&nbsp;Kaito Furuyama ,&nbsp;Yuan Yang ,&nbsp;Masaki Mito ,&nbsp;Hiroyuki Abe ,&nbsp;Rosanna Di Tinco ,&nbsp;Vincenzo Cardinale","doi":"10.1016/j.jcyt.2024.11.008","DOIUrl":"10.1016/j.jcyt.2024.11.008","url":null,"abstract":"<div><div>Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs. However, there is a lack of detailed guidance on selecting appropriate animal models for CGT therapies targeting specific pancreatic and liver conditions, such as pancreatitis and chronic liver diseases. In this review, the gastrointestinal committee for the International Society for Cell and Gene Therapy provides a summary of current recommendations for animal species and disease model selection, as outlined by the US Food and Drug Administration, with references to EU EMA and Japan PMDA. We discuss a range of small and large animal models, as well as humanized models, that are suitable for preclinical testing of CGT products aimed at treating pancreatic and liver diseases. For each model, we cover the associated pathophysiology, commonly used metrics for assessing disease status, the pros and limitations of the models, and the relevance of these models to human conditions. We also summarize the use and application of humanized mouse and other animal models in evaluating the safety and efficacy of CGT products. This review aims to provide comprehensive guidance for selecting appropriate animal species and models to help bridge the gap between the preclinical research and clinical trials using CGT therapies for specific pancreatic and liver diseases.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 259-278"},"PeriodicalIF":3.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933542","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":"Comparison of methotrexate dosing protocols for graft-versus-host disease prophylaxis after unrelated hematopoietic stem cell transplantation","authors":"Naokazu Nakamura ,&nbsp;Junya Kanda ,&nbsp;Tadakazu Kondo ,&nbsp;Toshiyuki Kitano ,&nbsp;Takashi Ikeda ,&nbsp;Kazunori Imada ,&nbsp;Ryosuke Takaya ,&nbsp;Tomoyo Kubo ,&nbsp;Satoshi Mitsuyuki ,&nbsp;Satoko Oka ,&nbsp;Akihito Yonezawa ,&nbsp;Tomoharu Takeoka ,&nbsp;Takashi Akasaka ,&nbsp;Masakatsu Hishizawa ,&nbsp;Kazuhiro Yago ,&nbsp;Hiroko Tsunemine ,&nbsp;Mitsumasa Watanabe ,&nbsp;Mitsuru Itoh ,&nbsp;Akifumi Takaori-Kondo ,&nbsp;Kyoto Stem Cell Transplantation Group (KSCTG)","doi":"10.1016/j.jcyt.2024.11.009","DOIUrl":"10.1016/j.jcyt.2024.11.009","url":null,"abstract":"<div><h3>Background aims</h3><div>Methotrexate (MTX) is used as standard graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation. However, the optimal dosing regimen among the various MTX regimens available remains unclear.</div></div><div><h3>Methods</h3><div>We used the registration data of Kyoto Stem Cell Transplantation Group to compare six MTX dosing protocols in a multicenter retrospective analysis of 816 cases of unrelated bone marrow or peripheral blood stem cell transplantation.</div></div><div><h3>Results</h3><div>Our findings indicated increased risks of grade Ⅱ–Ⅳ acute GVHD and extensive chronic GVHD in the cohort given the shortened mini-dose MTX regimen (5 mg/m² infusions on days 1, 3, and 6) compared with patients that received any of the other protocols. In addition, transplantation outcomes did not differ significantly between cohorts according to the inclusion or absence of leucovorin rescue.</div></div><div><h3>Conclusion</h3><div>The original short-term, reduced short-term, and mini-dose MTX methods were all effective for GVHD prophylaxis. However, omission of the day 11 MTX dose from the mini-dose regimen elevated the risks of grade Ⅱ–Ⅳ acute GVHD and extensive chronic GVHD. Moreover, leucovorin rescue might be ineffective in terms of reducing complications.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 307-315"},"PeriodicalIF":3.7,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802981","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":"Allogeneic hematopoietic stem cell transplantation using reduced intensity conditioning regimen for patients with acute myeloid leukemia not in complete remission","authors":"Yoshimitsu Shimomura ,&nbsp;Tetsuhisa Kitamura ,&nbsp;Masamitsu Yanada ,&nbsp;Shohei Mizuno ,&nbsp;Tadakazu Kondo ,&nbsp;Satoshi Yoshihara ,&nbsp;Masatsugu Tanaka ,&nbsp;Kazuki Inai ,&nbsp;Yuta Katayama ,&nbsp;Makoto Onizuka ,&nbsp;Takahiro Fukuda ,&nbsp;Hirohisa Nakamae ,&nbsp;Mineo Kurokawa ,&nbsp;Shingo Yano ,&nbsp;Miho Nara ,&nbsp;Masayoshi Masuko ,&nbsp;Shigesaburo Miyakoshi ,&nbsp;Tetsuya Eto ,&nbsp;Makoto Yoshimitsu ,&nbsp;Fumihiko Ishimaru ,&nbsp;Takaaki Konuma","doi":"10.1016/j.jcyt.2024.11.012","DOIUrl":"10.1016/j.jcyt.2024.11.012","url":null,"abstract":"<div><h3>Background</h3><div>Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment option for patients with refractory and relapsed acute myeloid leukemia (R/R AML) not in complete remission. Many studies investigating the prognosis of patients with R/R AML not in remission focused on patients who received myeloablative conditioning regimen (MAC). Conversely, reduced intensity conditioning regimen (RIC) could be a considerable conditioning regimen for some patients because of the high frequency of R/R AML in older patients who are not candidates for MAC.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate the prognosis and identify factors associated with outcomes in patients with R/R AML who underwent allogeneic HSCT with RIC.</div></div><div><h3>Study Design</h3><div>This study included 707 adult patients with AML not in complete remission who had received RIC. The primary endpoint was progression-free survival (PFS), which was estimated using the Kaplan–Meier method. Prognostic factors were identified using a Cox proportional hazards model with multiple imputations using a chained equation approach.</div></div><div><h3>Results</h3><div>The 5-year PFS, overall survival, relapse, and nonrelapse mortality were 18.8% (95% confidence interval [CI]: 15.6–22.2), 22.0% (95% CI: 8.5–25.7), 53.6% (95% CI 49.7–57.4%) and 27.5% (95% CI: 24.0–31.2), respectively. Multivariable analysis revealed that male sex, poor performance status, karyotype risk, and blasts in the peripheral blood were significantly associated with PFS.</div></div><div><h3>Conclusions</h3><div>This study identified prognostic factors in patients with R/R AML not in complete remission. These results can help to develop a transplant strategy for the treatment of R/R AML.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 316-323"},"PeriodicalIF":3.7,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774364","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":"Harnessing global HLA data for enhanced patient matching in iPSC haplobanks","authors":"Martin Maiers ,&nbsp;Stephen Sullivan ,&nbsp;Christopher McClain ,&nbsp;Christina Leonhard-Melief ,&nbsp;Marc L. Turner ,&nbsp;David Turner","doi":"10.1016/j.jcyt.2024.11.001","DOIUrl":"10.1016/j.jcyt.2024.11.001","url":null,"abstract":"<div><h3>Background</h3><div>Several countries have either developed or are developing national induced pluripotent stem cell (iPSC) banks of cell lines derived from donors with HLA homozygous genotypes (two identical haplotypes) prevalent in their local populations to provide immune matched tissues and cells to support regenerative medicine therapies. This ‘haplobank’ approach relies on knowledge of the HLA genotypes of the population to identify the most beneficial haplotypes for patient coverage, and ultimately identify donors or cord blood units carrying two copies of the target haplotype.</div></div><div><h3>Aims</h3><div>A potentially more efficient alternative to a national bank approach is to assess the haplotypes required to provide global patient coverage and to produce a single, global haplobank. Toward that end, we have developed an algorithm to prioritize HLA haplotypes that optimize coverage across the global population.</div></div><div><h3>Methods</h3><div>We analyzed data from eighteen countries participating in the Global Alliance for iPS Therapy (GAiT). A representative pool of HLA genotypes, reflecting the HLA of patients, was derived by sampling from each country's WMDA hematopoietic stem cell donor registry, or surrogate population. An algorithm was created based on HLA-A, -B and -DRB1 haplotype homozygous types with population HLA matching coverage defined by the absence of Host versus Graft (HvG) mismatches at these loci. HLA matching coverage was determined by iteratively selecting HLA haplotypes that provide the largest coverage against patient HLA genotypes sampled from the same population, excluding genotypes compatible with previous iterations.</div></div><div><h3>Results</h3><div>The top 10 haplotypes for each of the 18 countries were identified with patient coverage ranging from 19.5% in Brazil to 63.8% in Japan, with a mean coverage of 33.3%. In a ‘global’ model, utilizing the 180 most frequent haplotypes across all 18 populations (equivalent to 10 lines per country), the patient coverage ranged from 54.6% in India to 81.7% in Sweden, with a mean of 68.4%. Our findings demonstrate that global collaboration could more than double the potential for patient HLA matching coverage.</div></div><div><h3>Conclusions</h3><div>Interrogation of unrelated hematopoietic stem cell donor registry and cord blood bank HLA data demonstrated that HLA-A, -B, and -DRB1 homozygous donors for the top 180 global haplotypes are widely available. These results show that a globally coordinated strategy for haplobanking would reduce redundancy and allow more patients to be treated with the same investment.</div></div>","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"27 3","pages":"Pages 300-306"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882974","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":"Aims and Scope","authors":"","doi":"10.1016/S1465-3249(24)00909-5","DOIUrl":"10.1016/S1465-3249(24)00909-5","url":null,"abstract":"","PeriodicalId":50597,"journal":{"name":"Cytotherapy","volume":"26 12","pages":"Page A1"},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142660436","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}