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153. 509 - Health-Related Quality of Life (HRQL) Following Transplantation with Omidubicel Versus Umbilical Cord Blood (UCB) in Patients with Hematologic Malignancies: Results from a Phase III Randomized, Multicenter Study

Author

Horwitz, Mitchell E., Sajeev, Gautam, Stiff, Patrick, Brunstein, Claudio G., Cutler, Corey, Sanz, Guillermo, Lindemans, Caroline A., Rezvani, Andrew R., Hanna, Rabi, Koh, Liang Piu, Maziarz, Richard T, Khee Hwang, William Ying, Song, Yan, Liu, Qing, Manghani, Rocio, Sivaraman, Smitha, Signorovitch, James, and Galamidi-Cohen, Einat

Published
2022
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156. 127 - Fludarabine Exposure Predicts Outcome after CD19 CAR T Cell Therapy in Children and Young Adults with Acute Leukemia; An Exploratory, Observational Study

Author

Dekker, Linde, Calkoen, Friso, Jiang, Yilin, Blok, Hilly, Spoon, Maike, Admiraal, Rick, Hoogerbrugge, Peter, Vormoor, Britta, Vormoor, Josef, Zwaan, C. Michel, Visscher, Henk, Bierings, Marc, Van Der Vlugt, Marieke, Van Tinteren, Harm, Laura Nijstad, A., Huitema, Alwin D.R., Van Der Elst, Kim, Pieters, Rob, Lindemans, Caroline A., and Nierkens, Stefan

Published
2022
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157. 86 - Allogeneic Hematopoietic Stem Cell (Allo-HSCT) Transplant with Omidubicel Demonstrates Sustained Clinical Improvement Versus Standard Myeloablative Umbilical Cord Blood Transplantation (UCBT): Final Results of a Phase III Randomized, Multicenter Study

Author

Horwitz, Mitchell E., Stiff, Patrick, Cutler, Corey, Brunstein, Claudio G., Rezvani, Andrew R., Hanna, Rabi, Khee Hwang, William Ying, Maziarz, Richard T, McGuirk, Joseph P., Karras, Nicole, Lindemans, Caroline A., Valcarcel, David, Koh, Liang Piu, Schiller, Gary J., Sanz, Jaime, Schwarzbach, Aurelie, Galamidi-Cohen, Einat, and Sanz, Guillermo

Published
2022
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162. Bacterial blood stream infections (BSIs), particularly post-engraftment BSIs, are associated with increased mortality after allogeneic hematopoietic cell transplantation

Author

Ustun, Celalettin, primary, Young, Jo-Anne H., additional, Papanicolaou, Genovefa A., additional, Kim, Soyoung, additional, Ahn, Kwang Woo, additional, Chen, Min, additional, Abdel-Azim, Hisham, additional, Aljurf, Mahmoud, additional, Beitinjaneh, Amer, additional, Brown, Valerie, additional, Cerny, Jan, additional, Chhabra, Saurabh, additional, Kharfan-Dabaja, Mohamed A., additional, Dahi, Parastoo B., additional, Daly, Andrew, additional, Dandoy, Christopher E., additional, Dvorak, Christopher C., additional, Freytes, Cesar O., additional, Hashmi, Shahrukh, additional, Lazarus, Hillard, additional, Ljungman, Per, additional, Nishihori, Taiga, additional, Page, Kristin, additional, Pingali, Sai R. K., additional, Saad, Ayman, additional, Savani, Bipin N., additional, Weisdorf, Daniel, additional, Williams, Kirsten, additional, Wirk, Baldeep, additional, Auletta, Jeffery J., additional, Lindemans, Caroline A., additional, Komanduri, Krishna, additional, and Riches, Marcie, additional

Published
2018
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164. Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adults with Chronic Granulomatous Disease (CGD): A Study of the Inborn Errors Working Party (IEWP) of the EBMT

Author

Chiesa, Robert, primary, Wang, Junfeng, additional, Blok, Henric-Jan, additional, Neven, Benedicte, additional, Moshous, Despina, additional, Schulz, Ansgar, additional, Hoenig, Manfred, additional, Albert, Michael H., additional, Hauck, Fabian, additional, Al-Seraihy, Amal, additional, Gozdzik, Jolanta, additional, Ljungman, Per, additional, Lindemans, Caroline A., additional, Kalwak, Krzysztof, additional, Strahm, Brigitte, additional, Schanz, Urs, additional, Sedlacek, Petr, additional, Sykora, Karl-Walter, additional, Aksoylar, Serap, additional, Locatelli, Franco, additional, Stepensky, Polina, additional, Wynn, Robert, additional, Lum, Su Han, additional, Zecca, Marco, additional, Veys, Paul, additional, Gennery, Andrew, additional, Felber, Matthias, additional, Lankester, Arjan, additional, Guengoer, Tayfun, additional, and Slatter, Mary, additional

Published
2018
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165. New insights in phenotype and treatment of lung disease immuno-deficiency and chromosome breakage syndrome (LICS).

Author

Willemse, Brigitte W. M., van der Crabben, Saskia N., Kerstjens-Frederikse, Wilhelmina S., Timens, Wim, van Montfrans, Joris M., Lindemans, Caroline A., Boelens, Jaap Jan, Hennus, Marije P., and van Haaften, Gijs

Subjects
LUNG diseases, PLANT chromosomes, PHENOTYPES, THERAPEUTICS, CHROMOSOMES, DISEASE relapse
Abstract

We report five patients with lung disease immuno-deficiency and chromosome breakage syndrome (LICS) but without recurrent infections and severe immunodeficiency. One patient had extended survival to 6.5 years. Hematopoietic stem-cell transplantation failed to cure another patient. Our findings suggest that the immunological abnormalities can be limited and do not fully explain the LICS phenotype. [ABSTRACT FROM AUTHOR]

Published
2021
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166. Long-term effect of hematopoietic cell transplantation on systemic inflammation in patients with mucopolysaccharidoses

Author

van den Broek, Brigitte T.A., Lindemans, Caroline A., Boelens, Jaap Jan, Delemarre, Eveline M., Drylewicz, Julia, Verhoeven-Duif, Nanda, van Hasselt, Peter M., and Nierkens, Stefan

Abstract

Mucopolysaccharidoses (MPS) are devastating inherited diseases treated with hematopoietic cell transplantation (HCT). However, disease progression, especially skeletal, still occurs in all patients. Secondary inflammation has been hypothesized to be a cause. To investigate whether systemic inflammation is present in untreated patients and to evaluate the effect of HCT on systemic inflammation, dried blood spots (n = 66) of patients with MPS (n = 33) treated with HCT between 2003 and 2019 were included. Time points consisted of pre-HCT and, for patients with MPS type I (MPS I), also at 1, 3, and 10 years of follow-up. Ninety-two markers of the OLINK inflammation panel were measured and compared with those of age-matched control subjects (n = 31) by using principal component analysis and Wilcoxon rank sum tests with correction. Median age at transplantation was 1.3 years (range, 0.2-4.8 years), and median time of pre-HCT sample to transplantation was 0.1 year. Normal leukocyte enzyme activity levels were achieved in 93% of patients post-HCT. Pretransplant samples showed clear separation of patients and control subjects. Markers that differentiated pre-HCT between control subjects and patients were mainly pro-inflammatory (50%) or related to bone homeostasis and extracellular matrix degradation (33%). After 10 years' follow-up, only 5 markers (receptor activator of nuclear factor kappa-Β ligand, osteoprotegerin, axis inhibition protein 1 [AXIN1], stem cell factor, and Fms-related tyrosine kinase 3 ligand) remained significantly increased, with a large fold change difference between patients with MPS I and control subjects. In conclusion, systemic inflammation is present in untreated MPS patients and is reduced upon treatment with HCT. Markers related to bone homeostasis remain elevated up to 10 years after HCT and possibly reflect the ongoing skeletal disease, making them potential biomarkers for the evaluation of new therapies.

Published
2021
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167. 381 - Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Cerebral Adrenoleukodystrophy: Effects of Donor Cell Source and Match, Conditioning Regimen, and Stage of Cerebral Disease

Author

Boelens, Jaap Jan, Chiesa, Robert, Duncan, Christine N., Kühl, Jörn-Sven, Sevin, Caroline, Kapoor, Neena, Prasad, Vinod K., Lindemans, Caroline A., Jones, Simon A., Amartino, Hernan M., Algeri, Mattia, Bunin, Nancy J., Diaz-de-Heredia, Cristina, Shamir, Esther, Timm, Alison, Dietz, Andrew C., McNeil, Elizabeth, and Orchard, Paul J.

Published
2021
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168. 34 - Improved Clinical Outcomes with Omidubicel Versus Standard Myeloablative Umbilical Cord Blood Transplantation: Results of a Phase III Randomized, Multicenter Study

Author

Horwitz, Mitchell E., Cutler, Corey, Stiff, Patrick, Brunstein, Claudio G., Rezvani, Andrew R., Hanna, Rabi, Khee Hwang, William Ying, McGuirk, Joseph P., Karras, Nicole, Lindemans, Caroline A., Valcarcel, David, Maziarz, Richard T., Koh, Liang Piu, Schiller, Gary J., Khaled, Yasser, Hamerschlak, Nelson, Keating, Amy K, Frankfurt, Olga, Segalovich, Irit, Blackwell, Beth, Freedman, Laurence, and Galamidi, Einat

Published
2021
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169. Model-Based Dosing of Anti-Thymocyte Globulin in Pediatric Allogeneic Hematopoietic Cell Transplantation Improves Survival Chances: Updated Results from the Single Arm Phase II Parachute-Trial Combined with Real-World Data

Author

Admiraal, Rick, Nierkens, Stefan, Bierings, Marc, Belderbos, Mirjam, Huitema, Alwin D.R., Bredius, Robbert, Jiang, Yilin, Curran, Kevin J., Harris, Andrew C., Scaradavou, Andromachi, Cancio, Maria I., Klein, Elizabeth, Kollen, Wouter, Bresters, Dorine, Calkoen, Friso, Versluijs, A. Birgitta, Zwaan, Christian M., Boelens, Jaap-Jan, and Lindemans, Caroline A.

Abstract

Anti-thymocyte globulin (ATG) is used in the conditioning for pediatric hematopoietic cell transplantation (HCT) to prevent graft-versus-host-disease (GvHD) and graft failure (GF). Toxicity includes poor T-cell recovery, associated with viral reactivations and higher mortality. The PARACHUTE-trial1(non-randomized prospective trial investigating model-based dosing [MBD] compared to historical fixed dose of ATG Thymoglobulin) showed that MBD of ATG improves T-cell recovery compared to fixed dosing, while maintaining an anti-GvHD effect. We now evaluated outcome after 5-year follow-up combined with real-world data.

Published
2024
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170. Viral PCR Positivity in Stool before Allogeneic Hematopoietic Cell Transplantation is Strongly Associated with Acute Intestinal Graft-versus-Host Disease

Author

van Montfrans, Joris, Schulz, Laura, Versluys, Birgitta, de Wildt, Arianne, Wolfs, Tom, Bierings, Marc, Gerhardt, Corinne, Lindemans, Caroline, Wensing, Anne, and Boelens, Jaap Jan

Abstract

Acute graft-versus-host disease (aGVHD) can be triggered by inflammatory conditions, including infections and mucositis. We investigated the association between PCR positivity for gastrointestinal (GI) viruses in stool before hematopoietic cell transplantation (HCT) and intestinal aGVHD using Cox proportional hazard models. We included 48 consecutive HCT patients (28 with malignancies and 20 with nonmalignancies) without GI symptoms before HCT. Fifteen patients were GI virus positive: 9 adenovirus, 3 norovirus, 2 parechovirus, and 1 astrovirus. Overall survival was 58% ± 8%. The cumulative incidence of aGVHD grade 2 to 4 was 43% ± 8% (n = 18) after a median of 47 days (range, 14 to 140). In univariate analysis, GI virus PCR positivity was the only predictor for aGVHD (P = .008): within the group of GI virus PCR-positive patients, the cumulative incidence of aGVHD 2 to 4 was 70% ± 12% versus 29 ± 8% in the PCR-negative group (P = .004). In conclusion, GI virus PCR positivity before HCT predicted development of intestinal aGVHD. These results may ultimately affect monitoring, aGVHD prophylaxis, and treatment, as well as rescheduling of elective HCTs.

Published
2024
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171. Association of busulfan exposure and outcomes after HCT for patients with an inborn error of immunity

Author

Bognàr, Tim, Garcia-Rosa, Moises, Lalmohamed, Arief, Güngör, Tayfun, Hauri-Hohl, Mathias, Prockop, Susan, Oram, Layne, Pai, Sung-Yun, Brooks, Jordan, Savic, Rada M., Dvorak, Christopher C., Long-Boyle, Janel R., Krajinovic, Maja, Bittencourt, Henrique, Teyssier, Anne-Charlotte, Théorêt, Yves, Martinez, Cary, Egberts, Toine C. G., Morales, Erin, Slatter, Mary, Cuvelier, Geoffrey D. E., Chiesa, Robert, Wynn, Robert F., Coussons, Mary, Cicalese, Maria P., Ansari, Marc, Long, Susan E., Ebens, Christen L., Lust, Hannah, Chaudhury, Sonali, Nath, Christa E., Shaw, Peter J., Keogh, Steven J., van der Stoep, M. Y. Eileen C., Bredius, Robbert, Lindemans, Caroline A., Boelens, Jaap-Jan, and Bartelink, Imke H.

Abstract

•In patients with IEI, improved EFS and higher donor chimerism may be achieved by targeting a cumulative busulfan AUC of 80 mg × h/L.•The data stress the importance of uniformly using a validated population pharmacokinetic model to estimate the busulfan cumulative exposure.

Published
2024
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172. Bloodstream Infection Due to Vancomycin-resistant Enterococcus Is Associated With Increased Mortality After Hematopoietic Cell Transplantation for Acute Leukemia and Myelodysplastic Syndrome: A Multicenter, Retrospective Cohort Study.

Author

Papanicolaou, Genovefa A, Ustun, Celalettin, Young, Jo-Anne H, Chen, Min, Kim, Soyoung, Ahn, Kwang Woo, Komanduri, Krishna, Lindemans, Caroline, Auletta, Jeffery J, Riches, Marcie L, and Committee, CIBMTR® Infection and Immune Reconstitution Working

Subjects
CORD blood transplantation, MORTALITY risk factors, AGE distribution, BACTEREMIA, CONFIDENCE intervals, CYTOMEGALOVIRUS diseases, ENTEROCOCCUS, HEMATOPOIETIC stem cell transplantation, HOMOGRAFTS, LEUKEMIA, LONGITUDINAL method, MULTIVARIATE analysis, MYELODYSPLASTIC syndromes, PEDIATRICS, RISK assessment, SURVIVAL analysis (Biometry), TUMOR classification, ENTEROCOCCAL infections, VANCOMYCIN resistance, COMORBIDITY, RELATIVE medical risk, TREATMENT effectiveness, RETROSPECTIVE studies, ACUTE diseases, DISEASE complications
Abstract

Background We examined the impact of vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) on outcomes of allogeneic hematopoietic cell transplantation (HCT) utilizing the Center for International Blood and Marrow Transplant Research database. Methods Adult and pediatric patients (N = 7128) who underwent first HCT for acute leukemia or myelodysplastic syndrome from 2008 through 2012 were analyzed as 3 groups—VRE BSI, non-VRE BSI, without BSI—according to BSI status at 100 days (D100) after allogeneic HCT. Multivariable models examined the effect of VRE BSI for overall survival (OS) and nonrelapse mortality (NRM) at 1 year. Results Of 7128 patients, 258 (3.2%) had VRE BSI, 2398 (33.6%) had non-VRE BSI, and 4472 (63%) had no BSI. The median time to VRE BSI and non-VRE BSI were D11 and D15, respectively. Compared with non-VRE BSI patients, VRE BSI patients were older, had advanced-stage acute leukemia, and received umbilical cord blood (UCB) allografts. In multivariable models, VRE BSI was associated with lower OS (relative risk [RR], 2.9;(99% confidence interval [CI], 2.2–3.7) and increased NRM (RR, 4.7; 99% CI, 3.6–6.2) (P <.0001) for both. Other predictors for worse OS and increased NRM were non-VRE BSI, older age, advanced disease stage, UCB allograft, – mismatch, comorbidity index ≥3, and cytomegalovirus seropositivity (P <.001 for all variables). Conclusions VRE BSI is associated with lowest OS and highest NRM compared with patients without BSI or non-VRE BSI. Novel interventions that address the pathophysiology of VRE BSI have the potential of improving survival after HCT. [ABSTRACT FROM AUTHOR]

Published
2019
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174. Interferon-γ Mediates Direct Intestinal Stem Cell Damage in Gastrointestinal Graft-Versus-Host Disease

Author

Takashima, Shuichiro, primary, Bos, Joris, additional, Chandra, Daniel, additional, Jansen, Suze A., additional, O'Connor, Margaret, additional, Mertelsmann, Anna M., additional, Calafiore, Marco, additional, Egorova, Anastasiya, additional, Lo, Yuan-Hung, additional, Shroyer, Noah F., additional, Lindemans, Caroline A., additional, and Hanash, Alan M., additional

Published
2018
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177. The pulmonary metatranscriptome prior to pediatric HCT identifies post-HCT lung injury

Author

Zinter, Matt S., Lindemans, Caroline A., Versluys, Birgitta A., Mayday, Madeline Y., Sunshine, Sara, Reyes, Gustavo, Sirota, Marina, Sapru, Anil, Matthay, Michael A., Kharbanda, Sandhya, Dvorak, Christopher C., Boelens, Jaap J., and DeRisi, Joseph L.

Abstract

Lung injury after pediatric allogeneic hematopoietic cell transplantation (HCT) is a common and disastrous complication that threatens long-term survival. To develop strategies to prevent lung injury, novel tools are needed to comprehensively assess lung health in HCT candidates. Therefore, this study analyzed biospecimens from 181 pediatric HCT candidates who underwent routine pre-HCT bronchoalveolar lavage (BAL) at the University Medical Center Utrecht between 2005 and 2016. BAL fluid underwent metatranscriptomic sequencing of microbial and human RNA, and unsupervised clustering and generalized linear models were used to associate microbiome gene expression data with the development of post-HCT lung injury. Microbe-gene correlations were validated using a geographically distinct cohort of 18 pediatric HCT candidates. The cumulative incidence of post-HCT lung injury varied significantly according to 4 pre-HCT pulmonary metatranscriptome clusters, with the highest incidence observed in children with pre-HCT viral enrichment and innate immune activation, as well as in children with profound microbial depletion and concomitant natural killer/T-cell activation (P < .001). In contrast, children with pre-HCT pulmonary metatranscriptomes containing diverse oropharyngeal taxa and lacking inflammation rarely developed post-HCT lung injury. In addition, activation of epithelial-epidermal differentiation, mucus production, and cellular adhesion were associated with fatal post-HCT lung injury. In a separate validation cohort, associations among pulmonary respiratory viral load, oropharyngeal taxa, and pulmonary gene expression were recapitulated; the association with post-HCT lung injury needs to be validated in an independent cohort. This analysis suggests that assessment of the pre-HCT BAL fluid may identify high-risk pediatric HCT candidates who may benefit from pathobiology-targeted interventions.

Published
2021
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178. CD4+ T-cell reconstitution predicts survival outcomes after acute graft-versus-host-disease: a dual-center validation

Author

de Koning, Coco, Prockop, Susan, van Roessel, Ichelle, Kernan, Nancy, Klein, Elizabeth, Langenhorst, Jurgen, Szanto, Celina, Belderbos, Mirjam, Bierings, Marc, Boulad, Farid, Bresters, Dorine, Cancio, Maria, Curran, Kevin, Kollen, Wouter, O’Reilly, Richard, Scaradavou, Andromachi, Spitzer, Barbara, Versluijs, Birgitta, Huitema, Alwin, Lindemans, Caroline, Nierkens, Stefan, and Boelens, Jaap Jan

Abstract

Acute graft-versus-host-Disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). We previously showed that early CD4+ T-cell immune reconstitution (IR; CD4+ IR) predicts survival after HCT. Here, we studied the relation between CD4+ IR and survival in patients developing aGVHD. Pediatric patients undergoing first allogeneic HCT at University Medical Center Utrecht (UMC)/Princess Máxima Center (PMC) or Memorial Sloan Kettering Cancer Center (MSK) were included. Primary outcomes were nonrelapse mortality (NRM) and overall survival (OS), stratified for aGVHD and CD4+ IR, defined as ≥50 CD4+ T cells per μL within 100 days after HCT or before aGVHD onset. Multivariate and time-to-event Cox proportional hazards models were applied, and 591 patients (UMC/PMC, n = 276; MSK, n = 315) were included. NRM in patients with grade 3 to 4 aGVHD with or without CD4+ IR within 100 days after HCT was 30% vs 80% (P = .02) at UMC/PMC and 5% vs 67% (P = .02) at MSK. This was associated with lower OS without CD4+ IR (UMC/PMC, 61% vs 20%; P = .04; MSK, 75% vs 33%; P = .12). Inadequate CD4+ IR before aGVHD onset was associated with significantly higher NRM (74% vs 12%; P < .001) and inferior OS (24% vs 78%; P < .001). In this retrospective analysis, we demonstrate that early CD4+ IR, a simple and robust marker predictive of outcomes after HCT, is associated with survival after moderate to severe aGVHD. This association must be confirmed prospectively but suggests strategies to improve T-cell recovery after HCT may influence survival in patients developing aGVHD.

Published
2021
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179. CD4+T-cell reconstitution predicts survival outcomes after acute graft-versus-host-disease: a dual-center validation

Author

de Koning, Coco, Prockop, Susan, van Roessel, Ichelle, Kernan, Nancy, Klein, Elizabeth, Langenhorst, Jurgen, Szanto, Celina, Belderbos, Mirjam, Bierings, Marc, Boulad, Farid, Bresters, Dorine, Cancio, Maria, Curran, Kevin, Kollen, Wouter, O'Reilly, Richard, Scaradavou, Andromachi, Spitzer, Barbara, Versluijs, Birgitta, Huitema, Alwin, Lindemans, Caroline, Nierkens, Stefan, and Boelens, Jaap Jan

Abstract

Acute graft-versus-host-Disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). We previously showed that early CD4+T-cell immune reconstitution (IR; CD4+IR) predicts survival after HCT. Here, we studied the relation between CD4+IR and survival in patients developing aGVHD. Pediatric patients undergoing first allogeneic HCT at University Medical Center Utrecht (UMC)/Princess Máxima Center (PMC) or Memorial Sloan Kettering Cancer Center (MSK) were included. Primary outcomes were nonrelapse mortality (NRM) and overall survival (OS), stratified for aGVHD and CD4+IR, defined as ≥50 CD4+T cells per μL within 100 days after HCT or before aGVHD onset. Multivariate and time-to-event Cox proportional hazards models were applied, and 591 patients (UMC/PMC, n = 276; MSK, n = 315) were included. NRM in patients with grade 3 to 4 aGVHD with or without CD4+IR within 100 days after HCT was 30% vs 80% (P= .02) at UMC/PMC and 5% vs 67% (P= .02) at MSK. This was associated with lower OS without CD4+IR (UMC/PMC, 61% vs 20%; P= .04; MSK, 75% vs 33%; P= .12). Inadequate CD4+IR before aGVHD onset was associated with significantly higher NRM (74% vs 12%; P< .001) and inferior OS (24% vs 78%; P< .001). In this retrospective analysis, we demonstrate that early CD4+IR, a simple and robust marker predictive of outcomes after HCT, is associated with survival after moderate to severe aGVHD. This association must be confirmed prospectively but suggests strategies to improve T-cell recovery after HCT may influence survival in patients developing aGVHD.

Published
2021
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181. Excellent T-cell reconstitution and survival provided ATG exposure is low or absent after pediatric cord blood transplantation

Author

Admiraal, Rick, Lindemans, Caroline A, van Kesteren, Charlotte, Bierings, Marc B, Versluijs, A Birgitta, Nierkens, Stefan, and Boelens, Jaap Jan

Subjects
Journal Article, Clinical Trial
Abstract

Successful immune reconstitution (IR) is associated with improved outcomes following pediatric cord blood transplantation (CBT). Usage and timing of anti-thymocyte globulin (ATG), introduced to the conditioning to prevent graft-versus-host-disease and graft failure, negatively influences T-cell IR. We studied the relation between ATG exposure, IR and clinical outcomes. All pediatric patients receiving a first CBT between 2004-2015 at the University Medical Center Utrecht were included. ATG-exposure measures were determined with a validated PK-model. Main outcome of interest was early CD4+ IR, defined as CD4+ T-cell counts over 50x10(6)/L twice within 100 days after CBT. Other outcomes of interest included event free survival (EFS). Cox proportional-hazard and Fine-Gray competing-risk models were used. A total of 137 patients, median age of 7.4 years (range 0.2-22.7), were included, of whom 82% received ATG. Area under the curve (AUC) of ATG after infusion of the CB transplant predicted successful CD4+ IR. Adjusted probability on CD4+ IR was reduced with 26% for every 10 points increase in AUC after CBT (hazard ratio (HR) 0.974, p

Published
2016

183. Efficacy of MSC for steroid-refractory acute GVHD associates with MSC donor age and a defined molecular profile

Author

van der Wagen, Lotte E., Miranda-Bedate, Alberto, Janssen, Anke, Fernando, Febilla, Appukudige, Nagesha, van Dooremalen, Sanne, Westinga, Kasper, Admiraal, Rick, Lorenowicz, Magdalena J., Huls, Gerwin, Janssen, Jeroen J. W. M., Broers, Annoek E. C., van der Velden, Walter J. F. M., van Marwijk Kooy, Rien, Hazenberg, Mette D., de Haar, Colin, Lindemans, Caroline, Jan Boelens, Jaap, and Kuball, Jürgen

Published
2020
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184. RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury

Author

Fischer, Julius C., primary, Bscheider, Michael, additional, Eisenkolb, Gabriel, additional, Lin, Chia-Ching, additional, Wintges, Alexander, additional, Otten, Vera, additional, Lindemans, Caroline A., additional, Heidegger, Simon, additional, Rudelius, Martina, additional, Monette, Sébastien, additional, Porosnicu Rodriguez, Kori A., additional, Calafiore, Marco, additional, Liebermann, Sophie, additional, Liu, Chen, additional, Lienenklaus, Stefan, additional, Weiss, Siegfried, additional, Kalinke, Ulrich, additional, Ruland, Jürgen, additional, Peschel, Christian, additional, Shono, Yusuke, additional, Docampo, Melissa, additional, Velardi, Enrico, additional, Jenq, Robert R., additional, Hanash, Alan M., additional, Dudakov, Jarrod A., additional, Haas, Tobias, additional, van den Brink, Marcel R. M., additional, and Poeck, Hendrik, additional

Published
2017
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190. IL-33 Induces Paneth Cell Production of EGF and Soluble ST2, Regulating Epithelial Regeneration after Intestinal Injury

Author

Calafiore, Marco, Fu, YA-Yuan, Vinci, Paola, Arnhold, Viktor, Chang, Winston, Jansen, Suze, Egorova, Anastasiya, Takashima, Shuichiro, Kuttiyara, Jason, Ito, Takahiro, Serody, Jonathan, Nakae, Susumu, Turnquist, Heth, van Es, Johan, Clevers, Hans, Lindemans, Caroline A., Blazar, Bruce R, and Hanash, Alan M.

Abstract

Crypt base intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but their frequencies are reduced in experimental models of graft vs. host disease (GVHD). Paneth cells provide an epithelial contribution to the stem cell niche, but their frequencies are also reduced in GVHD mouse models and in patients with GVHD. Mechanisms regulating ISCs and their niche after damage remain poorly understood. Interleukin-33 (IL-33) is an immunomodulatory alarmin typically thought to target lymphocytes such as T cells and innate lymphoid cells. In experimental models of allogeneic bone marrow transplantation, IL-33 can promote or attenuate GVHD, depending on the cellular target and the timing of the exposure. A secreted isoform of the IL-33 receptor, termed soluble ST2 (sST2), acts as a negative regulator by blocking IL-33 from binding to the membrane-bound isoform that mediates intracellular signaling. sST2 also has diagnostic and prognostic utility, serving as a biomarker for GVHD severity. While IL-33 has well-described effects on lymphocytes populations, there is limited understanding of the role of IL-33 signaling within the intestinal mucosa after damage.

Published
2023
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191. Clonal Hematopoiesis Is Common in Long-Term Survivors of Pediatric Hematopoietic Cell Transplantation, Including Umbilical Cord Blood Transplantation

Author

Müskens, Konradin F., van Bergen, Maaike G.J.M., de Graaf, Aniek O., Wieringa, Nienke, te Pas, Brigit M., Pagter, Anne P.J. de, Bense, Joëll E., Lankester, Arjan C., Kremer, Leontien C.M., Jansen, Joop H., Huls, Geert A., Nierkens, Stefan, Lindemans, Caroline A., and Belderbos, Mirjam E.

Abstract

Background

Published
2023
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192. Definitions, incidence and outcome of poor graft function after hematopoietic cell transplantation: A systematic review and meta-analysis.

Author

Müskens, Konradin F., Lindemans, Caroline A., Dandis, Rana, Nierkens, Stefan, and Belderbos, Mirjam E.

Abstract

Poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (HCT) is a serious complication with high morbidity and mortality. The reported incidence of PGF, its risk factors and outcome vary substantially between studies. This variability may be explained by heterogeneity in patient cohorts and HCT strategies, differences in the underlying causes of cytopenia, as well as by differences in PGF definition. In this systematic review and meta-analysis, we provide an overview of the various PGF definitions used and determined the impact of this variability on the reported incidence and outcome. We searched MEDLINE, EMBASE and Web of Science up to July 2022, for any study on PGF in HCT recipients. We performed random-effect meta-analyses for incidence and outcome and subgroup analyses based on different PGF criteria. Among 69 included studies (14.265 HCT recipients), we found 63 different PGF definitions, using various combinations of 11 common criteria. The median incidence of PGF was 7% (IQR: 5–11%, 22 cohorts). The pooled survival of PGF patients was 53% (95% CI: 45–61%, 23 cohorts). The most commonly reported risk factors associated with PGF were history of cytomegalovirus infection and prior graft-versus-host disease. Incidence was lower in studies with strict cytopenic cutoffs, while survival was lower for primary compared to secondary PGF. This work indicates that a standardized, quantitative definition of PGF is needed to facilitate clinical guideline development and to advance scientific progress. • Definitions of poor graft function (PGF) are heterogeneous across studies. • Definition heterogeneity affects the reported incidence and outcome of PGF. • A standardized, quantitative and evidence-based definition of PGF is required. • A standardized definition facilitates progress in understanding and treating PGF. [ABSTRACT FROM AUTHOR]

Published
2023
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193. Erratum: Corrigendum: Gut microbiome–derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease

Author

Mathewson, Nathan D, primary, Jenq, Robert, additional, Mathew, Anna V, additional, Koenigsknecht, Mark, additional, Hanash, Alan, additional, Toubai, Tomomi, additional, Oravecz-Wilson, Katherine, additional, Wu, Shin-Rong, additional, Sun, Yaping, additional, Rossi, Corinne, additional, Fujiwara, Hideaki, additional, Byun, Jaeman, additional, Shono, Yusuke, additional, Lindemans, Caroline, additional, Calafiore, Marco, additional, Schmidt, Thomas C, additional, Honda, Kenya, additional, Young, Vincent B, additional, Pennathur, Subramaniam, additional, van den Brink, Marcel, additional, and Reddy, Pavan, additional

Published
2016
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194. Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation

Author

Ballen, Karen, primary, Woo Ahn, Kwang, additional, Chen, Min, additional, Abdel-Azim, Hisham, additional, Ahmed, Ibrahim, additional, Aljurf, Mahmoud, additional, Antin, Joseph, additional, Bhatt, Ami S., additional, Boeckh, Michael, additional, Chen, George, additional, Dandoy, Christopher, additional, George, Biju, additional, Laughlin, Mary J., additional, Lazarus, Hillard M., additional, MacMillan, Margaret L., additional, Margolis, David A., additional, Marks, David I., additional, Norkin, Maxim, additional, Rosenthal, Joseph, additional, Saad, Ayman, additional, Savani, Bipin, additional, Schouten, Harry C., additional, Storek, Jan, additional, Szabolcs, Paul, additional, Ustun, Celalettin, additional, Verneris, Michael R., additional, Waller, Edmund K., additional, Weisdorf, Daniel J., additional, Williams, Kirsten M., additional, Wingard, John R., additional, Wirk, Baldeep, additional, Wolfs, Tom, additional, Young, Jo-Anne H., additional, Auletta, Jeffrey, additional, Komanduri, Krishna V., additional, Lindemans, Caroline, additional, and Riches, Marcie L., additional

Published
2016
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195. Gut microbiome–derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease

Author

Mathewson, Nathan D, primary, Jenq, Robert, additional, Mathew, Anna V, additional, Koenigsknecht, Mark, additional, Hanash, Alan, additional, Toubai, Tomomi, additional, Oravecz-Wilson, Katherine, additional, Wu, Shin-Rong, additional, Sun, Yaping, additional, Rossi, Corinne, additional, Fujiwara, Hideaki, additional, Byun, Jaeman, additional, Shono, Yusuke, additional, Lindemans, Caroline, additional, Calafiore, Marco, additional, Schmidt, Thomas M, additional, Honda, Kenya, additional, Young, Vincent B, additional, Pennathur, Subramaniam, additional, van den Brink, Marcel, additional, and Reddy, Pavan, additional

Published
2016
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196. Predictable Fast CD4+ Reconstitution and Prevention of Graft Failure in High-Risk Patients following Cord Blood Transplantation by Individualized Dosing and Therapeutic Drug Monitoring of Anti-Thymocyte Globulin

Author

Admiraal, Rick, primary, van Kesteren, Charlotte, additional, Raaij, Lysette Ebskamp-van, additional, Lacna, Amelia M., additional, Versluys, Birgitta, additional, Bierings, Marc, additional, Lindemans, Caroline A., additional, Nierkens, Stefan, additional, and Boelens, Jaap-Jan, additional

Published
2016
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