Biology of Blood and Marrow Transplantation最新文献

{"title":"Volume of Gadolinium Enhancement and Successful Repair of the Blood-Brain Barrier in Cerebral Adrenoleukodystrophy","authors":"Troy C. Lund ,&nbsp;Michelle Ng ,&nbsp;Paul J. Orchard ,&nbsp;Daniel J. Loes ,&nbsp;Gerald V. Raymond ,&nbsp;Ashish Gupta ,&nbsp;Dan Kenny-Jung ,&nbsp;David R. Nascene","doi":"10.1016/j.bbmt.2020.06.019","DOIUrl":"10.1016/j.bbmt.2020.06.019","url":null,"abstract":"<div><p>Up to 40% of boys with adrenoleukodystrophy develop a severe central nervous system demyelinating form (cALD) characterized by white matter changes and gadolinium enhancement on magnetic resonance imaging (MRI). Hematopoietic cell transplant (HCT) is the only proven means to attenuate cALD progression. The elimination of active neuroinflammation is indicated radiographically by the resolution of gadolinium (Gd) enhancement and correlates to speed of donor neutrophil recovery. We analyzed 66 boys with cALD undergoing HCT for biomarkers correlating with early (30 days post-HCT) Gd signal resolution. We found that log Gd volume (cm³) on pre-HCT MRI strongly positively correlated to day 30 Gd resolution (<em>P</em> = .0003) with smaller volume correlating to higher proportion resolved, as was the baseline gadolinium intensity score (<em>P</em> = .04), plasma chitotriosidase activity (<em>P</em> = .04), and faster absolute neutrophil count recovery (<em>P</em> = .03). In multivariate analysis, log Gd volume remained superior in determining which patients would have Gd signal resolution by 30 days post-HCT (<em>P</em> = .016). A final analysis indicated that early Gd resolution also correlated with less neurologic progression from baseline to 1 year following HCT (<em>P</em> = .006). MRI Gd volume may serve as a contributing biomarker to better delineate outcomes and an important metric in comparing therapies in the treatment of cALD.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.06.019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38098459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Nonrelapse Mortality after HLA-Matched Related 2-Step Hematopoietic Stem Cell Transplantation Using Cyclophosphamide for Graft-versus-Host Disease Prophylaxis and the Potential Impact of Non- Cyclophosphamide-Exposed T Cells on Outcomes","authors":"Dolores Grosso ,&nbsp;Matthew Carabasi ,&nbsp;Joanne Filicko-O'Hara ,&nbsp;John L. Wagner ,&nbsp;William O'Hara ,&nbsp;Michael Sun ,&nbsp;Beth Colombe ,&nbsp;W. Shi ,&nbsp;Maria Werner-Wasik ,&nbsp;Shannon Rudolph ,&nbsp;Onder Alpdogan ,&nbsp;Adam Binder ,&nbsp;Margaret Kasner ,&nbsp;Thomas Klumpp ,&nbsp;Ubaldo Martinez-Outschoorn ,&nbsp;Neil Palmisiano ,&nbsp;Lindsay Wilde ,&nbsp;Pierluigi Porcu ,&nbsp;Usama Gergis ,&nbsp;Neal Flomenberg","doi":"10.1016/j.bbmt.2020.06.021","DOIUrl":"10.1016/j.bbmt.2020.06.021","url":null,"abstract":"<div><p>The use of cyclophosphamide (CY) for bidirectional tolerization of recipient and donor T cells is associated with reduced rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after HLA-matched hematopoietic stem cell transplantation (HSCT). However, recurrent disease remains the primary barrier to long-term survival. We extended our 2-step approach to HLA-matched related HSCT using a radiation-based myeloablative conditioning regimen combined with a high dose of T cells in an attempt to reduce relapse rates while maintaining the beneficial effects of CY tolerization. After conditioning, patients received their grafts in 2 components: (1) a fixed dose of 2 × 10⁸/kg T cells, followed 2 days later by CY, and (2) a CD34-selected graft containing a small residual amount of non-CY-exposed T cells, at a median dose of 2.98 × 10³/kg. Forty-six patients with hematologic malignancies were treated. Despite the myeloablative conditioning regimen and use of high T cell doses, the cumulative incidences of grade II-IV acute GVHD, chronic GVHD, and NRM at 1 year and 5 years were very low, at 13%, 9%, and 4.3%, respectively. This contributed to a high overall survival of 89.1% at 1 year and 65.8% at 5 years. Relapse was the primary cause of mortality, with a cumulative incidence of 23.9% at 1 year and 45.7% at 5 years. In a post hoc analysis, relapse rates were significantly lower in patients receiving greater than versus those receiving less than the group median of non-CY-exposed residual T cells in the CD34 product (19.3% versus 58.1%; <em>P</em> = .009), without a concomitant increase in NRM. In its current form, this 2-step regimen was highly tolerable, but strategies to reduce relapse, potentially the addition of T cells not exposed to CY, are needed.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.06.021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38128914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suppression of Hematopoietic Primitive Cells in Patients with Secondary Failure of Platelet Recovery after Acute Graft-versus-Host Disease","authors":"Aijie Huang,&nbsp;Xiaoming Zhao,&nbsp;Meizhang Li,&nbsp;Gusheng Tang,&nbsp;Yang Fei,&nbsp;Roujia Wang,&nbsp;Lei Gao,&nbsp;Xiong Ni,&nbsp;Weiping Zhang,&nbsp;Jianmin Yang,&nbsp;Xiaoxia Hu,&nbsp;Jianmin Wang","doi":"10.1016/j.bbmt.2020.06.003","DOIUrl":"10.1016/j.bbmt.2020.06.003","url":null,"abstract":"<div><p>Secondary failure of platelet recovery (SFPR) can occur after allogeneic hematopoietic stem cell transplantation (alloHSCT), and 20% of cases are related to acute graft-versus-host disease (aGVHD). The underlying mechanisms of this association are unclear, however. The aim of the present study was to investigate the potential mechanisms of SFPR secondary to aGVHD, which may provide a new therapeutic strategy for these patients. A total of 468 patients with malignant hematologic disease who underwent alloHSCT were included. Sixty-six patients developed SFPR after alloHSCT, and in 45 of these 66 patients (68.2%), SFPR was secondary to grade II-IV aGVHD (SFPR/aGVHD). Compared with patients with good graft function (GGF), patients with SFPR had poor overall survival (20.72% versus 88.01%; <em>P &lt;</em> .0001). Grade II-IV aGVHD was identified as an independent risk factor for SFPR in multivariate analysis (hazard ratio, 9.512; <em>P &lt;</em> .0001). We observed reduced erythroid and megakaryocyte colony formation in bone marrow (BM) samples isolated from SFPR/aGVHD patients, consistent with the lower frequency of megakaryocyte and erythrocyte progenitors in BM. Levels of the inflammatory cytokines IL-2R and TNF-R1 were significantly higher in the SFPR/aGVHD group compared with the GGF group (<em>P</em> = .002 and .001, respectively), as were the frequencies of proinflammatory T helper subsets. Furthermore, the pathways that regulate hematopoiesis and immune responses were universally underexpressed in CD34⁺ cells isolated from SFPR/aGVHD patients. Differentially expressed genes were significantly enriched in the hematopoietic cell lineage pathway and other pathways involved in both immune responses and megakaryopoiesis. In summary, we found that both the immune microenvironment and compromised proliferation of hematopoietic primitive cells contribute to the development of SFPR secondary to aGVHD, and our data provide new insight into the mechanisms of SFPR in the context of aGVHD.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.06.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38045682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation and Management of Bone Mineral Density Following Hematopoietic Cell Transplantation: A Survey of Current Practice by the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation","authors":"Nina Salooja ,&nbsp;Hildegaard Greinix ,&nbsp;Tapani Ruutu ,&nbsp;Steffie van der Werf ,&nbsp;Anja van Biezen ,&nbsp;Anita Lawitschka ,&nbsp;Grzegorz Basak ,&nbsp;Rafael Duarte","doi":"10.1016/j.bbmt.2020.06.022","DOIUrl":"10.1016/j.bbmt.2020.06.022","url":null,"abstract":"<div><p>Reduced bone mineral density (BMD) is a well-recognized complication of hematopoietic cell transplantation (HCT), with significant drops in BMD occurring within the first 12 months after HCT. Guidance on identifying and managing this complication is available in several published guidelines. In this study, we investigated current practices in the investigation and management of low BMD in centers registered with the European Society for Blood and Marrow Transplantation (EBMT). A questionnaire about bone health was sent to all registered centers, and responses were received from 99 centers in 25 countries (52%) currently registered with the EBMT. Our data highlight considerable heterogeneity in practices across European centers in relation to investigations, management, and use of guidelines. Our data demonstrate the need for better dissemination and implementation of existing guidelines and also for the development of multidisciplinary guidelines with input from all relevant stakeholders.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1083879120303979/pdfft?md5=92314f167250d6ea920712c0b5fe8f40&pid=1-s2.0-S1083879120303979-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38123520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Mortality after Autologous Transplant: Development of a Novel Risk Score","authors":"Mariano Berro ,&nbsp;Saurabh Chhabra ,&nbsp;José Luis Piñana ,&nbsp;Jorge Arbelbide ,&nbsp;Maria M. Rivas ,&nbsp;Ana Lisa Basquiera ,&nbsp;Adriana Vitriu ,&nbsp;Alejandro Requejo ,&nbsp;Vera Milovic ,&nbsp;Sebastian Yantorno ,&nbsp;Gonzalo Bentolila ,&nbsp;Juan Jose Garcia ,&nbsp;Martin Castro ,&nbsp;Silvina Palmer ,&nbsp;Martin Saslavsky ,&nbsp;Patricio Duarte ,&nbsp;Amalia Cerutti ,&nbsp;Gustavo Jarchum ,&nbsp;Matias Tisi Baña ,&nbsp;Bicky Thapa ,&nbsp;Gustavo Kusminsky","doi":"10.1016/j.bbmt.2020.06.028","DOIUrl":"10.1016/j.bbmt.2020.06.028","url":null,"abstract":"<div><p>There have been several efforts to predict mortality after autologous stem cell transplantation (ASCT), such as the hematopoietic cell transplant-comorbidity index (HCT-CI), described for allogeneic stem cell transplantation and validated for ASCT, but there is no composite score in the setting of ASCT combining comorbidities with other clinical characteristics. Our aim is to describe a comprehensive score combining comorbidities with other clinical factors and to analyze the impact of this score on nonrelapse mortality (NRM), overall survival (OS), and early morbidity endpoints (mechanical ventilation, shock or dialysis) after ASCT. For the training cohort, we retrospectively reviewed data of 2068 adult patients who received an ASCT in Argentina (October 2002 to June 2017) for multiple myeloma or lymphoma. For the validation cohort, we analyzed 2168 ASCTs performed in the Medical College of Wisconsin and Spanish stem cell transplant group (Grupo Español de Trasplante Hematopoyético (GETH)) (January 2012 to December 2018). We first performed a multivariate analysis for NRM in order to select and assign weight to the risk factors included in the score (male patients, aged 55 to 64 and ≥65 years, HCT-CI ≥3, Hodgkin lymphoma and non-Hodgkin lymphoma). The hazard ratio for NRM increased proportionally with the score. Patients were grouped as low risk (LR) with a score of 0 to 1 (686, 33%), intermediate risk (IR) with a score of 2 to 3 (1109, 53%), high risk (HR) with a score of 4 (198, 10%), and very high risk (VHR) with a score of ≥5 (75, 4%). The score was associated with a progressive increase in all the early morbidity endpoints. Moreover, the score was significantly associated with early NRM (day 100: 1.5% versus 2.4% versus 7.6% versus 17.6%) as well as long term (1 to 3 years; 1.8% to 2.3% versus 3.8% to 4.9% versus 11.7% to 14.5% versus 25.0% to 27.4%, respectively; <em>P</em>&lt; .0001) and OS (1 to 5 years; 94% to 73% versus 89% to 75% versus 76% to 47% versus 65% to 52% respectively; <em>P</em> &lt; .0001). The score was validated in an independent cohort (N = 2168) and was significantly associated with early and late events. In conclusion, we developed and validated a novel score predicting NRM and OS in 2 large cohorts of more than 2000 autologous transplant patients. This tool can be useful for tailoring conditioning regimens or defining risk for transplant program decision making.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.06.028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38138135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Black Lives and Black Donors Matter Post-Hematopoietic Stem Cell Transplantation","authors":"Mitchell S. Cairo","doi":"10.1016/j.bbmt.2020.08.007","DOIUrl":"10.1016/j.bbmt.2020.08.007","url":null,"abstract":"","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.08.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38255032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ixazomib for Chronic Graft-versus-Host Disease Prophylaxis following Allogeneic Hematopoietic Cell Transplantation","authors":"Saurabh Chhabra ,&nbsp;Alexis Visotcky ,&nbsp;Marcelo C. Pasquini ,&nbsp;Fenlu Zhu ,&nbsp;Xiaoying Tang ,&nbsp;Mei-Jie Zhang ,&nbsp;Robert Thompson ,&nbsp;Sameem Abedin ,&nbsp;Anita D'Souza ,&nbsp;Binod Dhakal ,&nbsp;William R. Drobyski ,&nbsp;Timothy S. Fenske ,&nbsp;James H. Jerkins ,&nbsp;J. Douglas Rizzo ,&nbsp;Lyndsey Runaas ,&nbsp;Wael Saber ,&nbsp;Nirav N. Shah ,&nbsp;Bronwen E. Shaw ,&nbsp;Mary M. Horowitz ,&nbsp;Parameswaran N. Hari ,&nbsp;Mehdi Hamadani","doi":"10.1016/j.bbmt.2020.07.005","DOIUrl":"10.1016/j.bbmt.2020.07.005","url":null,"abstract":"<div><p>Chronic graft-versus-host disease (cGVHD) is major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Ixazomib is an oral, second-generation, proteasome inhibitor that has been shown in preclinical models to prevent GVHD. We conducted a phase I/II trial in 57 patients to evaluate the safety and efficacy of ixazomib administration for cGVHD prophylaxis in patients undergoing allogeneic HCT. Oral ixazomib was administered on a weekly basis for a total of 4 doses, beginning days +60 through +90, to recipients of matched related donor (MRD, n = 25) or matched unrelated donor (MUD, n = 26) allogeneic HCT in phase II portion of the study, once the recommended phase II dose of 4 mg was identified in phase I (n = 6). All patients received peripheral blood graft and standard GVHD prophylaxis of tacrolimus and methotrexate. Ixazomib administration was safe and well tolerated, with thrombocytopenia, leukopenia, gastrointestinal complaints, and fatigue the most common adverse events (&gt;10%). In phase II (n = 51), the cumulative incidence of cGVHD at 1 year was 36% (95% confidence interval [CI], 19% to 54%) in the MRD cohort and 39% (95% CI, 21% to 56%) in the MUD cohort. One-year cumulative incidence of nonrelapse mortality (NRM) and relapse was 0% and 20% (95% CI, 8% to 36%) in the MRD cohort, respectively. In the MUD cohort, the respective NRM and relapse rates were 4% (0% to 16%) and 34% (17% to 52%). The outcomes on the study were compared post hoc with contemporaneous matched Center for International Blood and Marrow Transplant Research (CIBMTR) controls. This post hoc analysis showed no significant improvement in cGVHD rates in both the MRD (hazard ratio [HR] = 0.85, <em>P</em> = .64) or MUD cohorts (HR = 0.68, <em>P</em> = .26) on the study compared with CIBMTR controls. B cell activating factor plasma levels were significantly higher after ixazomib dosing in those who remained cGVHD free compared with those developed cGVHD. This study shows that the novel strategy of short-course oral ixazomib following allogeneic HCT is safe but did not demonstrate significant improvement in cGVHD incidence in recipients of MRD and MUD transplantation compared with matched CIBMTR controls. This study is registered at <span>www.clinicaltrials.gov</span><svg><path></path></svg> as NCT02250300.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38143804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Busulfan Pharmacokinetics in Adenosine Deaminase-Deficient Severe Combined Immunodeficiency Gene Therapy","authors":"Kathryn L. Bradford ,&nbsp;Siyu Liu ,&nbsp;Maja Krajinovic ,&nbsp;Marc Ansari ,&nbsp;Elizabeth Garabedian ,&nbsp;John Tse ,&nbsp;Xiaoyan Wang ,&nbsp;Kit L. Shaw ,&nbsp;H. Bobby Gaspar ,&nbsp;Fabio Candotti ,&nbsp;Donald B. Kohn","doi":"10.1016/j.bbmt.2020.07.004","DOIUrl":"10.1016/j.bbmt.2020.07.004","url":null,"abstract":"<div><p>The pharmacokinetics of low-dose busulfan (BU) were investigated as a nonmyeloablative conditioning regimen for autologous gene therapy (GT) in pediatric subjects with adenosine deaminase-deficient severe combined immunodeficiency disease (ADA SCID). In 3 successive clinical trials, which included either γ-retroviral (γ-RV) or lentiviral (LV) vectors, subjects were conditioned with BU using different dosing nomograms. The first cohort received BU doses based on body surface area (BSA), the second cohort received doses based on actual body weight (ABW), and in the third cohort, therapeutic drug monitoring (TDM) was used to target a specific area under the concentration-time curve (AUC). Neither BSA-based nor ABW-based dosing achieved a consistent cumulative BU AUC; in contrast, TDM-based dosing led to more consistent AUC. BU clearance increased as subject age increased from birth to 18 months. However, weight and age alone were insufficient to accurately predict the dose that would consistently achieve a target AUC. Furthermore, various clinical, laboratory, and genetic factors (eg, genotypes for glutathione-S-transferase isozymes known to participate in BU metabolism) were analyzed, but no single finding predicted subjects with rapid versus slow clearance. Analysis of BU AUC and the postengraftment vector copy number (VCN) in granulocytes, a surrogate marker of the level of engrafted gene-modified hematopoietic stem and progenitor cells (HSPCs), demonstrated gene marking at levels sufficient for therapeutic benefit in the subjects who had achieved the target BU AUC. Although many factors determine the ultimate engraftment following GT, this work demonstrates that the BU AUC correlated with the eventual level of engrafted gene-modified HSPCs within a vector group (γ-RV versus LV), with significantly higher levels of granulocyte VCN in the recipients of LV-modified grafts compared to recipients of γ-RV-transduced grafts. Taken together, these findings provide insight into low-dose BU pharmacokinetics in the unique setting of autologous GT for ADA SCID, and these dosing principles may be applied to future GT trials using low-dose BU to open the bone marrow niche.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.07.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38143806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preconditioning Absolute Lymphocyte Count and Transplantation Outcomes in Matched Related Donor Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Reduced-Intensity Conditioning and Antithymocyte Globulin Treatment","authors":"Go-Un Woo ,&nbsp;Junshik Hong ,&nbsp;Hyangseon Kim ,&nbsp;Ja Min Byun ,&nbsp;Youngil Koh ,&nbsp;Dong-Yeop Shin ,&nbsp;Inho Kim ,&nbsp;Sung-Soo Yoon","doi":"10.1016/j.bbmt.2020.06.005","DOIUrl":"10.1016/j.bbmt.2020.06.005","url":null,"abstract":"<div><p>The integration of antithymocyte globulin (ATG) into therapy has significantly reduced the incidence of graft-versus-host disease (GVHD) and is being actively used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The ATG dosage is determined by the recipient's body weight, but some insist that this approach does not reflect the actual target of ATG. In this respect, weight-based dosing may lead to ATG overdose, particularly in recipients with a relatively low absolute lymphocyte count (ALC). We retrospectively analyzed 84 patients with acute leukemia or myelodysplastic syndrome who underwent matched related donor (MRD) allo-HSCT with reduced-intensity conditioning (RIC) at a single institution. Patients were dichotomized according to the ALC measured on the first day of conditioning (day -7) to investigate the associations of the ALC with GVHD and survival outcomes. The median duration of follow-up was 29 months. The preconditioning ALC was closely correlated with the ALC at the first ATG administration (day -3). The cumulative incidences of both acute GVHD and chronic GVHD were significantly lower in the preconditioning ALC &lt;500/μL group compared with the ALC ≥500/μL group. There was no significant difference in disease relapse incidence between the 2 groups; however, mortality was significantly higher in the ALC &lt;500/μL group. Multivariate analysis including disease status, modified European Blood and Marrow Transplantation score, and preconditioning ALC (≥500/μL versus &lt;500/μL) identified disease status and ALC as being independently associated with overall survival (OS). In particular, infection was the most common cause of death in the ALC &lt;500/μL group. Our data suggest that uniform weight-based ATG dosing in MRD allo-HSCT with RIC is associated with an increase in nonrelapse mortality and a relatively inferior OS in patients with a significantly low preconditioning ALC. Therefore, alternative strategies for the integration of ATG should be considered in allo-HSCT, at least for patients with a substantially low preconditioning ALC.</p></div>","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.bbmt.2020.06.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38068644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Masthead (Purpose and Scope)","authors":"","doi":"10.1016/S1083-8791(20)30546-2","DOIUrl":"https://doi.org/10.1016/S1083-8791(20)30546-2","url":null,"abstract":"","PeriodicalId":9165,"journal":{"name":"Biology of Blood and Marrow Transplantation","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S1083-8791(20)30546-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137414309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}