Transplantation and Cellular Therapy最新文献

{"title":"Corrigendum to 'Risk Factors for Bronchiolitis Obliterans Syndrome after Initial Detection of Pulmonary Impairment after Hematopoietic Cell Transplantation' [Transplantation and Cellular Therapy 29/3 (2023) 204-204].","authors":"Mansour Alkhunaizi, Badar Patel, Luis Bueno, Neel Bhan, Tahreem Ahmed, Muhammad H Arain, Rima Saliba, Gabriela Rondon, Burton F Dickey, Lara Bashoura, David E Ost, Liang Li, Shikun Wang, Elizabeth Shpall, Richard E Champlin, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Amin M Alousi, Ajay Sheshadri","doi":"10.1016/j.jtct.2024.10.013","DOIUrl":"10.1016/j.jtct.2024.10.013","url":null,"abstract":"","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676950","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":"Early mixed donor chimerism is a strong negative prognostic indicator in allogeneic stem cell transplant for AML and MDS.","authors":"Michael Radford, Alejandro Garcia-Horton, Rohail Badami, Elaine Jin, Nida Usmani, Daria Grafodatskaya, Elizabeth McCready, Dina Khalaf, Irwin Walker, Brian Leber, Kylie Lepic, Gregory Pond, Tobias Berg","doi":"10.1016/j.jtct.2024.11.006","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.11.006","url":null,"abstract":"<p><strong>Background: </strong>Allogeneic bone marrow transplantation remains the most potent curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) due to the graft-versus-tumor effect provided by donor cells. Donor chimerism is utilized early after transplantation to evaluate engraftment and to monitor the persistence of donor hematopoiesis.</p><p><strong>Objective(s): </strong>Literature is conflicting regarding to the prognostic utility of early mixed donor chimerism, chimerism kinetic patterns as well as factors associated with it and we sought to clarify this uncertainty.</p><p><strong>Study design: </strong>In this single-centre retrospective analysis, 141 adults aged 18 years of age or older with AML (n=104) and MDS (n=37) who received their first transplant from HLA matched related, matched unrelated or mismatched related (haploidentical) donors between 2016 and 2022 and had at least day 30 chimerism measured were included. Approximately 30% received post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis and 67% of subjects received reduced-intensity conditioning. Chimerism was measured using STR-PCR from unfractionated peripheral blood mononuclear cells (whole blood; WB) and CD3+ (T cell; TC) compartment at each time point. Complete donor chimerism was defined as ≥95% whereas <95% defined as mixed. Competing risk analysis was used to estimate cumulative incidence of relapse with kinetic calculations completed using an increment factor. Kaplan-Meier was used for overall survival (OS) and relapse-free survival (RFS). Cox proportional hazards regression was used to explore prognostic factors for OS and RFS.</p><p><strong>Results: </strong>Both day 30 mixed WB and TC donor chimerism were individually associated with an increased risk of relapse and worse overall and relapse-free survival at days 30, 60 and 90 post-transplant. Day 30 mixed WB was more specific for relapse (86%), while mixed TC was more sensitive (67%). Complete day 30 chimerism had a negative predictive value of 63% and 70% and positive predictive value of 57% and 67% for WB and TC, respectively. Day 30 WB and TC donor chimerism of <88.92% and 89.29% had specificities of 79.17% and 82.19% although sensitivities only approximated 50%. Evaluating the kinetics of chimerism over the first 90 days provided additional information for prognosticating relapse than absolute chimerism values at individual time points in both WB day 30 to 90 [HR, 1.75 (95% CI, 1.04-2.94); p<0.035] and TC day 60 to 90 [HR, 1.32 (95% CI, 1.03, 1.69); p<0.29]. Twice as many patients with complete chimerism developed acute GVHD compared to those with mixed chimerism. Factors that were found to be associated with day 30 mixed TC chimerism were donor source, ATG GVHD prophylaxis, myeloablative conditioning and female sex, while only donor source was associated with mixed WB.</p><p><strong>Conclusions: </strong>Both TC and WB day 30 mixed chimerism wer","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640000","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":"Factors Associated with Increased Risk of Contamination in Bone Marrow Transplants.","authors":"Eashwar Somasundaram, Rachel Gill, Nicole Hartford, Kerry Collier, Steven M McAfee, Bimalangshu R Dey, Areej El-Jawahri, Zachariah DeFilipp, Matthew Frigault, Mark Leick, Richard Newcomb, Paul V O'Donnell, Yi-Bin Chen, Thomas R Spitzer","doi":"10.1016/j.jtct.2024.11.002","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.11.002","url":null,"abstract":"<p><strong>Introduction: </strong>Hematopoietic cell transplantation (HCT) remains the definitive therapeutic modality for numerous malignant and non-malignant hematologic disorders. Conventional bone marrow remains a viable donor source for HCT. However, microbial contamination of bone marrow harvests may present a risk to immunocompromised recipients. This analysis sought to identify clinical factors associated with bone marrow contamination.</p><p><strong>Methods: </strong>We analyzed a single institution experience comprising 667 unique bone marrow harvests collected between 1999 and 2021. We trended the yearly microbial contamination rate over this time span. Harvest type (autologous vs allogenic), donor age, donor sex, physician experience, total nucleated cell (TNC) count, volume collected, and TNC concentration were included in a univariate (UV) and multivariate (MV) logistic model to assess which factors were associated with contamination.</p><p><strong>Results: </strong>Males comprised 55.8% of the donor population and the median age of the cohort was 35 [IQR: 27-45]. There were 19 autologous, 151 related allogenic, and 497 unrelated allogenic transplants in this cohort. 87 of the 667 (13.0%) harvests were contaminated and essentially all contaminants were common skin flora. The yearly contamination rates displayed substantial variability, ranging from 0% to 42.9%, with no discernible trend. Harvest type did not exhibit a significant association with contamination risk. However, male donor sex was found to be significantly associated with a higher contamination rate (18%) compared to female sex (6.8%, p < 0.001). In both UV and MV logistic models, male sex emerged as the sole factor linked to contamination risk (OR: 2.90, 95% CI: 1.65 - 5.35).</p><p><strong>Conclusion: </strong>This analysis represents the largest single center investigation of bone marrow harvest microbial contamination rates. Notably, it is the first to establish an association between contamination and male donor sex. We propose that this association may be attributed to differences in skin flora composition or innate immune function between sexes, general hygiene practices or possibly the result of the frequent clipping of body hair in males prior to the harvest procedure. Further research is warranted to explore the underlying mechanisms and clinical implications of this novel finding.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629031","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":"Systematic Review and Meta-Analysis of Extracorporeal Photopheresis for the Treatment of Steroid-Refractory Chronic Graft-Versus-Host Disease.","authors":"Zachariah DeFilipp, Laura Fox, Tobias A W Holderried, Varun Mehra, David Michonneau, Alex Pashley, Andrei Karlsson, Dennis Dong Hwan Kim","doi":"10.1016/j.jtct.2024.11.004","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.11.004","url":null,"abstract":"<p><p>The objective of this meta-analysis (MA) was to evaluate the efficacy and safety of extracorporeal photopheresis (ECP) for the treatment of steroid-refractory chronic graft-versus-host disease (SR-cGvHD). A systematic literature review (SLR) was conducted according to PRISMA guidelines, followed by a feasibility assessment (FA) to assess potential between-study heterogeneity in the meta-analysis (MA). Random-effects MAs were performed for overall survival (OS), failure-free survival (FFS), overall response rate (ORR) and skin-specific response. A subgroup analysis was conducted to explore the effect of NIH assessment criteria. The SLR identified 627 records; 45 unique studies were ultimately included in the MA. For patients treated with ECP, at Month 12, the pooled OS rate was 83.97% and the pooled FFS rate was 60.79%. ORR was 45.34% at Months 3-4 and 58.23% at Months 6-8. Subgroup analyses showed no significant difference in ORR between studies utilizing NIH criteria and those utilizing non-NIH criteria. Skin-specific response was 34.86% at Months 2-3 and 54.22% at Months 4-6. There was considerable heterogeneity across all analyses, with I² values ranging from 65% to 91%. This SLR and MA indicates that ECP results in favorable outcomes in the treatment of SR-cGvHD, including OS, FFS and ORR.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628947","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":"Outpatient management of patients conditioned with Fludarabine and Treosulfan prior to allogeneic hematopoietic cell transplantation.","authors":"Johanne Skovgaard Schovsbo, Lars Kjeldsen, Kristina Holmegaard Nørskov, Henrik Sengeløv, Brian Thomas Kornblit, Ida Schjødt, Søren Lykke Petersen, Marietta Nygaard, Niels Smedegaard Andersen, Bo Kok Mortensen, Lone Smidstrup Friis","doi":"10.1016/j.jtct.2024.11.001","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.11.001","url":null,"abstract":"<p><strong>Background: </strong>Allogenic hematopoietic cell transplantation (allo-HCT) with myeloablative conditioning traditionally requires 30 days long hospitalizations after stem cell infusion. However, advancements in supportive and prophylactic care have allowed for a trend towards outpatient management of allo-HCT, potentially leading to improved patient quality of life and increased procedure cost-effectiveness. In 2014, Fludarabine and Treosulfan (FluTreo) conditioning was introduced as a myeloablative regimen with reduced toxicity at Copenhagen University Hospital, Rigshospitalet (CUH). After gaining experience with the regimen, an outpatient program was established. This study shares the outcome of outpatient conditioning with FluTreo allo-HCT at CUH.</p><p><strong>Objective: </strong>To investigate safety and feasibility of outpatient FluTreo allo-HCT. Furthermore, to investigate the potentially enhanced cost-effectiveness of outpatient allo-HCT primarily through reduction in hospitalization days compared to the 30 days hospitalization associated with standard myeloablative conditioning.</p><p><strong>Study design: </strong>This retrospective study included all patients undergoing FluTreo allo-HCT due to malignant diseases (n = 124) at CUH from 2018 to 2022. Patients received outpatient treatment (n = 91) unless certain circumstances required planned hospitalization (n = 33). As conditioning, patients received intravenous Fludarabine 90 mg/m² and Treosulfan either 30 or 42 g/m². Statistical analyses included descriptive statistics and Kaplan Meier survival analysis.</p><p><strong>Results: </strong>The median duration of hospitalization in the outpatient group was 4 days (Q1-Q3 0-12.5) from day -6 to +28 compared to a median of 28 days (Q1-Q3 26-34) in the inpatient group. 32 (35%) in the outpatient group did not require hospitalization within day +28 after transplantation. The remaining 59 patients (65%) were hospitalized after 12 days (Q1-Q3 7-16 days) from start of conditioning, for a median of 10 days (Q1-Q3 5-18). The outpatient group required significantly less IV antibiotics, IV opioids and parenteral nutrition than the inpatient group, despite no difference in treatment toxicity, acute graft-versus-host disease, or relapse between the groups. The outpatient group experienced no early deaths during the first 3 months after transplantation and 1-year non-relapse mortality was 6%.</p><p><strong>Conclusion: </strong>Outpatient allo-HCT with FluTreo conditioning is feasible and safe in a selected group of patients, significantly reducing hospitalization days without compromising patient outcomes. Outpatient FluTreo allo-HCT potentially stands as a more cost-effective and patient-friendly alternative compared to traditional in-patient management.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628942","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":"Effect of ABO Mismatch and RBC Alloimmunization on the Outcome of Hematopoietic Cell Transplantation for Sickle Cell Disease.","authors":"Israa Saib, Bader Alahmari, Husam Alsadi, Ahmed Alaskar, Ayman Hejazi, Hind Salama, Abdulrahman Al Raiza, Abdullah S Al Saleh, Ayman Ibrahim, Mohammed Bakkar, Ghori A, Ahmed Alsuhaibani, Ahmed Alharbi, Tahani Alanazi, Rasha Ahmed, Inaam Shehabeddine, Suha Alkhraisat, Amani Alharbi, Isam Mahasneh, Maybelle Ballili, Zied Aljubour, Mazen Ahmed, Mohsen Alzahrani","doi":"10.1016/j.jtct.2024.11.003","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.11.003","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hematopoietic cell transplantation (HCT) remains the only well-established curative option for sickle cell disease (SCD) patients. Nonmyeloablative (NMA) conditioning has been used to improve the outcomes and reduce toxicities in adult SCD patients. However, Recipient/Donor (R/D) ABO incompatibility and alloimmunization could be significant impediments to successful outcomes when transplanting SCD patients due to risks of hemolysis, delayed engraftment, poor graft function and graft failure (GF). Herein, we report our experience with allogeneic HSCT for SCD and the effects of RBC groups mismatch and alloimmunization on the outcome of transplanted patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We conducted a retrospective analysis of all SCD patients (age &gt;14 year) that underwent HSCT from January 2015 to February 2022 at our center. All patients received Intravenous alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy TBI on day -2 or -1 for conditioning. Pre-transplant preparation consisted of hydroxyurea at maximum tolerated dose for 2-3 months and one session of exchange transfusion. Peripherally mobilized CD34 stem cells targeting 10 × 10&lt;sup&gt;6&lt;/sup&gt; /kg of recipient weight were used. For graft versus host disease (GVHD) prophylaxis sirolimus was started on day -1 and continued for one year with tapering if lymphoid chimerism was &gt; 50%. For Patients with major ABO incompatibility, we administered 2 doses of rituximab (375 mg/m2) and 3 sessions of plasmapheresis before starting the conditioning regimen targeting an isoheamagglutinin titer &lt; 1/32. The primary objective was to determine the impact of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. The secondary objective was to assess the impact of GF on overall survival (OS). Logistic regression was done to evaluate predictors for GF. Kaplan-Meier method was used for survival analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 194 patients were included with a median age of 26 years. The median baseline Hgb and HbS were 93 g/L and 71.3%, respectively. Indications of stem cell transplantations were most commonly due to recurrent vaso-occlusive crisis in 52.5% of patients, CNS events in 19.6%, and acute chest syndrome in 17%. After a median follow up of 28.8 months (5-83), sixteen patients (8%) experienced graft failure (3 with primary GF and 13 with secondary GF). On univariate analysis, ABO minor incompatibility and RBC alloantibodies against donor non-ABO antigens were predictive for GF.On multivariate analysis RBC alloantibodies against donor non-ABO antigens (OR, 8.29; 95% CI, 2.01 to 34.05, P=0.0033) was the only factor predictive of GF. None of the 16 patients with major ABO incompatibility developed GF. Two-years OS for all patients was 95%. The 2 years OS for patients without GF was 98% compared to 74% in patients with GF, (P&lt;0.0001).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;In our SCD transplanted patients, RBC al","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629025","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":"Venous thromboembolism incidence and risk factors in patients undergoing hematopoietic stem cell transplantation.","authors":"Miranda Benfield, Jiaxian He, Justin Arnall, Whitney Kaizen, Elizabeth Jandrisevits, Karine Eboli-Lopes, Brandy Dodd, Michael R Grunwald, Belinda Avalos, Edward Copelan, Jai N Patel","doi":"10.1016/j.jtct.2024.10.016","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.10.016","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Malignancy is a well-known risk factor for venous thromboembolism (VTE), and the Khorana risk score is effective for screening solid tumor patients. However, there is a lack of validated screening tools and established risk factors for patients undergoing hematopoietic stem cell transplant (HCT). Current literature reports VTE incidence in HCT patients ranging from 2.5% to 8.5%. Anticoagulation is difficult to manage post-transplant given prolonged thrombocytopenia and the likelihood of bleeding. By identifying risk factors, a predictive model may be developed to prospectively test prophylaxis strategies in patients at the highest thromboembolic event (TE) risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study evaluated the cumulative incidence of TE at 6 months following allogeneic and autologous HCTs. This study also aimed to identify risk factors for developing TE, to evaluate time from HCT to TE, and to compare one-year survival following HCT between patients experiencing TE and those who did not.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design: &lt;/strong&gt;This is a retrospective single-center study evaluating the incidence of TE events in adult subjects undergoing HCT between March 2014 and December 2019. ICD-9 and ICD-10 codes were used to determine cancer diagnosis, TE events up 180 days after HCT, and comorbidities of interest. Each subject was reviewed for data accuracy by manual retrospective chart review. The study employed statistical tests such as the cumulative incidence method with competing risks, Gray's test, and univariate and multivariate Cox proportional hazards models to analyze the time to first thromboembolic (TE) event, evaluate risk factors, and assess 1-year survival post-HCT in relation to TE events within 180 days of HCT. Variables examined included age, sex, body mass index (BMI), transplant type, hospital length of stay, history of TE prior to transplant, active infections, graft-versus-host disease (GVHD), veno-occlusive disorder (VOD), cytomegaly virus (CMV) and other factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study included 636 evaluable patients; the majority were male (57.9%), white (68.7%), and underwent an autologous HCT (68.4%). Twenty-nine patients (4.6%) experienced a TE event within 180 days post-transplant. TE events were more common in the allogeneic transplant group (n=13/201, 6.5%) than the autologous transplant group (n=16/435, 3.7%) (p=0.122). The cumulative incidence of TE was higher in patients who developed an active infection than those who did not (7.6% vs 3.1%, P=.011). Hospital LOS [HR 1.03, 95% CI 1.0-1.06, p=0.036] and active infection [HR 2.34, 95% CI 1.1-4.95, p=0.027] were significantly associated with TE in the univariate analysis but were not retained in the final multivariate model. There was no difference in one-year survival among all patients who experienced a TE event and those who did not; however, in the autologous HCT subgroup, one-year survival rate was significantly lo","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590789","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":"NOVEL DRUG COMBINATIONS AND DONOR LYMPHOCYTE INFUSIONS ALLOW PROLONGED DISEASE CONTROL IN MULTIPLE MYELOMA PATIENTS RELAPSING AFTER ALLOGENEIC TRANSPLANT: New treatments for Multiple Myeloma patients relapsing after Allo transplant.","authors":"Chiara Nozzoli, Martina Pucillo, Luisa Giaccone, Alessandro Rambaldi, Maria Teresa Lupo Stanghellini, Edoardo Benedetti, Domenico Russo, Nicola Mordini, Silvia Mangiacavalli, Paolo Bernasconi, Matteo Parma, Paola Carluccio, Piero Galieni, Paolo Rivela, Massimo Martino, Patrizia Chiusolo, Miriam Isola, Maria De Martino, Elena Oldani, Eliana Degrandi, Riccardo Boncompagni, Elisabetta Antonioli, Fabrizio Carnevale, Monica Tozzi, Carmine Selleri, Renato Fanin, Francesca Patriarca","doi":"10.1016/j.jtct.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.jtct.2024.10.015","url":null,"abstract":"<p><strong>Background: </strong>Even if allogeneic stem cell transplantation (allo-SCT) is curative for a minority of patients with multiple myeloma (MM), the patients who have relapsed after allo-SCT can experience long-term survival, suggesting a synergy between anti-myeloma drugs administered after allo-SCT and donor T cells.</p><p><strong>Objectives: </strong>We retrospectively evaluated the outcome of MM patients reported to the \"Gruppo Italiano Trapianto Midollo Osseo e Terapia Cellulare\" (GITMO) network, who underwent allo-SCTs between 2009 and 2018 in order to identify predictors for long-term outcome in the whole population (242 patients) and for prolonged overall survival (OS) after relapse in the subgroup of relapsed patients (118 patients).</p><p><strong>Results: </strong>At a median follow-up of 40.9 months after allo-SCT median OS and progression free survival (PFS) of the whole population were respectively 39.4 and 19.0 months from allo-SCT. The cumulative incidence (CI) of non-relapse mortality (NRM) was 10.3 % at one year and 27.6% at five years. Grade 2-4 acute GVHD CI was 19.8% and 5-year CI of moderate or severe chronic GVHD was 31.8%. In the multivariate model older age at transplant (p=0.020), treatment with more than 2 lines of therapy before allo-SCT (p=0.003) and transplant from unrelated or haploidentical donor (p=0.025) were significant factors associated with reduced OS. Relapse after allo-SCT occurred in 118 (59%) patients at a median of 14.3 months (IQR 7.2-26.9). Twenty (17%) received only steroids, radiotherapy or supportive care, 41 (35%) received 1 line, 23 (19%) 2 lines and 34 patients (29%) 3 or 4 lines of salvage treatment. Nine patients were exclusively treated with chemotherapy, 9 received at least one salvage treatment including immunomodulating agents (Imids), 43 patients were treated with at least one rescue therapy including proteasome inhibitors (PIs) and 37 patients received at least one salvage treatment including monoclonal antibodies (33 daratumumab, 1 elotuzumab, 1 isatuximab, 2 belantamab). Median OS of relapsed patients was 38.5 months from allo-SCT and 20.2 months from relapse. In multivariate analysis, OS after relapse was significantly prolonged in patients with a longer time to relapse after allo-SCT (time to relapse 6-24 months p=0.016; time to relapse ≥ 24 months p< 0.001) and in those who had received at least 3 salvage treatment lines (p<0.036) and donor lymphocyte infusions (DLI) (p=0.020).</p><p><strong>Conclusions: </strong>In our study, patients transplanted in early phases of disease and with HLA identical sibling donors had the best chance of long-term survival. Late relapse after allo-SCT, multiple courses of salvage treatment and the association with DLI could allow long disease control in patients who experienced relapse after allo-SCT.</p>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590776","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":"Hospital Associated Disability among Older Adults with Plasma Cell Disorders Receiving Autologous Stem Cell Transplant","authors":"","doi":"10.1016/j.jtct.2024.06.014","DOIUrl":"10.1016/j.jtct.2024.06.014","url":null,"abstract":"<div><div>Increasing number of older adults with Plasma Cell Disorders (PCDs) are receiving autologous stem cell transplant (ASCT) in the US. Hospital associated disability (HAD) is a common complication associated with acute care hospitalization among older adults. To estimate the prevalence and prognostic significance of HAD among older adults with MM undergoing ASCT. This retrospective cohort study used consecutive adults ≥ 18 y with PCD receiving ASCT at a single institution between 1/2013 and 5/2023. Trained nursing staff assessed Katz Activities of Daily Living (ADL) at admission and every 3 days thereafter under our Virtual Acute Care for Elders program. The primary outcome was development of HAD defined as ≥1 point decline on the Katz Activities of Daily Living (ADL) scale from hospital admission to discharge. We examined the association between putative risk factors such as age, Karnofsky performance status (KPS), baseline ADL score, Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) and HAD using modified Poisson regression models with robust variance estimators. Subsequently, we studied the impact of HAD on downstream adverse events including 30-day readmission rates and long term survival. We included 778 adults with a median age of 62 y (QR 56-68 y), with 56% males and 55% non-Hispanic Whites. In the overall population, 112 (14.4%) developed HAD, with much higher incidence among older adults ≥ 65 y compared to those &lt;65 y at ASCT (22% vs. 9%, <em>P</em> value &lt; .01). In multivariable analysis, increasing age (RR 1.56; 95% CI 1.25-1.94, per 10 y increase), female sex (RR 1.79; 95% CI 1.27-2.53) and KPS ≤ 70 (RR 2.55; 95% CI 1.32-4.94) were associated with an increased risk of developing HAD. As compared to those without, patients with HAD had a two-fold higher risk of 30-day readmission (95% CI 1.16-3.39) and a 3.7-fold increased risk of all-cause mortality (95% CI 2.15-6.22). Nearly one in 4 older adults ≥ 65 y developed HAD while undergoing ASCT which was associated with a two-fold increased risk of 30-day readmission. Interventions to prevent HAD and its downstream consequences are critically needed.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1086.e1-1086.e7"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321714","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":"Melphalan Dose in Combination With Fludarabine Affects Gastrointestinal Toxicity and Graft-Versus-Host Disease After Allogeneic Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndromes","authors":"Omar Albanyan ,&nbsp;Hany Elmariah ,&nbsp;Denise Kalos ,&nbsp;Jongphil Kim ,&nbsp;Rawan Faramand ,&nbsp;David Sallman ,&nbsp;Asmita Mishra ,&nbsp;Kendra Sweet ,&nbsp;Lia Perez ,&nbsp;Jose Ochoa-Bayona ,&nbsp;Michael Nieder ,&nbsp;Rami Komrokji ,&nbsp;Jeffery Lancet ,&nbsp;Hugo Fernandez ,&nbsp;Taiga Nishihori ,&nbsp;Joseph Pidala ,&nbsp;Claudio Anasetti ,&nbsp;Nelli Bejanyan","doi":"10.1016/j.jtct.2024.08.007","DOIUrl":"10.1016/j.jtct.2024.08.007","url":null,"abstract":"<div><div>Fludarabine (Flu) and melphalan (Mel) reduced-intensity conditioning is frequently used for allogenic hematopoietic cell transplant (allo-HCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, there is limited evidence on the impact of Mel dosing on toxicities and clinical outcomes of allo-HCT. We retrospectively compared 8/8 HLA-matched donor allo-HCT outcomes of 345 patients with AML or MDS receiving total Mel dose of 100 mg/m² (Mel-100, <em>n</em> = 62) versus 140 mg/m² (Mel-140, <em>n</em> = 283) in combination with Flu. Median age at allo-HCT was 66 years and median follow-up was 36.5 months. For Mel-100 versus Mel-140 groups, any grade gastrointestinal (GI) toxicity rates were 40.3% versus 67.8% (<em>P</em> &lt; .001), day 100 grade II to IV acute graft-versus-host disease (GVHD) rates were 21.0% versus 43.1% (<em>P</em> = .001) and 2-year chronic GVHD rates were 17.4% versus 27.1% (<em>P</em> = .033). In multivariable analysis, Mel-140 resulted in higher risks of GI toxicity (HR = 1.83, <em>P</em> = .013), grade II to IV acute GVHD (HR=2.35, <em>P</em> = .003), and moderate/severe chronic GVHD (HR = 3.13, <em>P</em> = .007). Total Mel dose had no independent impact on oral mucositis, nonrelapse mortality, relapse, relapse-free survival, and overall survival. While independent validation of our observation is warranted, our findings support using Mel-100 in combination with Flu to minimize allo-HCT toxicities and morbidities related to GVHD.</div></div>","PeriodicalId":23283,"journal":{"name":"Transplantation and Cellular Therapy","volume":"30 11","pages":"Pages 1090.e1-1090.e10"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989002","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}