77 results on '"Kröger, N."'
Search Results
2. Cost analysis of patients undergoing allogeneic stem cell transplantation or chimeric antigen receptor T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma from a German healthcare payer perspective
- Author
-
Ahmadi, P., Ghandili, S., Jakobs, F., Konnopka, C., Morgner-Miehlke, A., Kröger, N., and Ayuk, F.
- Published
- 2024
- Full Text
- View/download PDF
3. Upper and/or Lower Respiratory Tract Infection Caused by Human Metapneumovirus After Allogeneic Hematopoietic Stem Cell Transplantation
- Author
-
Piñana, J.L., Tridello, G., Xhaard, A., Wendel, L., Montoro, J., Vazquez, L., Heras, I., Ljungman, P., Mikulska, M., Salmenniemi, U., Perez, A., Kröger, N., Cornelissen, J, Sala, E., Martino, R., Geurten, C., Byrne, J., Maertens, J., Kerre, T., Martin, M, Pascual, M.J., Yeshurun, M., Finke, J., Groll, A.H., Shaw, P.J., Blijlevens, N.M.A., Arcese, W., Ganser, A., Suarez-Lledo, M., Alzahrani, M., Choi, G., Forcade, E., Paviglianiti, A., Solano, C., Wachowiak, J., Zuckerman, T., Bader, P., Clausen, J., Mayer, J., Schroyens, W., Metafuni, E., Knelange, N., Averbuch, D., Camara, R. de la, Piñana, J.L., Tridello, G., Xhaard, A., Wendel, L., Montoro, J., Vazquez, L., Heras, I., Ljungman, P., Mikulska, M., Salmenniemi, U., Perez, A., Kröger, N., Cornelissen, J, Sala, E., Martino, R., Geurten, C., Byrne, J., Maertens, J., Kerre, T., Martin, M, Pascual, M.J., Yeshurun, M., Finke, J., Groll, A.H., Shaw, P.J., Blijlevens, N.M.A., Arcese, W., Ganser, A., Suarez-Lledo, M., Alzahrani, M., Choi, G., Forcade, E., Paviglianiti, A., Solano, C., Wachowiak, J., Zuckerman, T., Bader, P., Clausen, J., Mayer, J., Schroyens, W., Metafuni, E., Knelange, N., Averbuch, D., and Camara, R. de la
- Abstract
Contains fulltext : 304925.pdf (Publisher’s version ) (Closed access), BACKGROUND: Human metapneumovirus (hMPV) epidemiology, clinical characteristics and risk factors for poor outcome after allogeneic stem cell transplantation (allo-HCT) remain a poorly investigated area. METHODS: This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allo-HCT. RESULTS: We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. CONCLUSIONS: These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases.
- Published
- 2024
4. Current strategies of cell and gene therapy for solid tumors: results of the joint international ESMO and CTIWP-EBMT survey.
- Author
-
Comoli, P., Pentheroudakis, G., Ruggeri, A., Koehl, U., Lordick, F., Mooyaart, J.E., Hoogenboom, J.D., Urbano-Ispizua, A., Peters, S., Kuball, J., Kröger, N., Sureda, A., Chabannon, C., Haanen, J., and Pedrazzoli, P.
- Subjects
- *
GENE therapy , *CELLULAR therapy , *TUMORS - Published
- 2024
- Full Text
- View/download PDF
5. Outcomes of Haploidentical Transplants with PT-CY versus 10/10 MUD Transplants with ATG in Germany.
- Author
-
Arslan A, Labuhn S, Sala E, Ringhoffer M, Schetelig J, Schroeder T, Bug G, Franke GN, Stelljes M, Dreger P, Zeiser R, Teschner D, Bethge WA, Eder M, Edinger M, Amann EM, Neuchel C, Schmid-Möglich A, Schmeller S, Beyersmann J, Schrezenmeier H, Mytilineos J, Kröger N, and Fuerst D
- Abstract
Allogeneic stem cell transplantation (alloHSCT) is the best curative treatment modality for many malignant haematological disorders. In the absence of a matched related donor (MRD), matched unrelated donors (MUD) and haploidentical donors (Haplo-Tx) are the most important sources of stem cells. However, multicenter real-life data which compare 10/10 MUD transplantations with Haplo-Tx is still limited. In this registry based retrospective study, we compared the outcomes of alloHSCTs from 10/10 MUD with anti-thymocyte globulin (ATG) based regimens (n=7050) versus Haplo-Tx using post-transplant cyclophosphamide (PT-CY Haplo) (n=487) in adult patients with haematological malignancies between 2010 and 2020. Cox proportional hazard models and competing risks regression models were formed to compare the outcomes of the groups. OS, DFS and GRFS were superior for 10/10 MUD (OS: HR 1.27, CI 1.10- 1.47, p=0.001, DFS: HR 1.17, CI 1.02-1.34, p=0.022, GRFS: HR 1.34, CI 1.19-1.50, p<0.001). Risk for aGVHD grade II-IV, aGVHD grade III-IV and cGVHD was higher in the PT-CY Haplo group compared to the 10/10 MUD group (aGVHD grade II-IV: HR 1.46, CI 1.25- 1.71, p<0.001; aGVHD grade III-IV: HR 1.74, CI 1.37- 2.20, p<0.001 and cGVHD: HR 1.30, CI 1.11-1.51, p=0.001). A lower incidence of relapse was observed in the PT-CY Haplo group (relapse: HR 0.83, CI 0.69-0.99, p=0.038). Unrelated 10/10 matched transplantation with ATG treatment leads to lower GvHD rates and improved survival rates when compared to PT-CY Haplo transplantation in Germany., (Copyright © 2024 American Society of Hematology.)
- Published
- 2024
- Full Text
- View/download PDF
6. Hope for motherhood: pregnancy after allogeneic hematopoietic cell transplantation (a national multicenter study).
- Author
-
Sockel K, Neu A, Goeckenjan M, Ditschkowski M, Hilgendorf I, Kröger N, Ayuk FA, Stoelzel F, Middeke JM, Eder M, Bethge W, Finke J, Bertz H, Kobbe G, Kaufmann M, Platzbecker U, Beverungen D, Schmid C, von Bonin M, Egger-Heidrich K, Heberling L, Trautmann-Grill K, Teipel R, Bug G, Tischer J, Fraccaroli A, Fante M, Wolff D, Luft T, Winkler J, Schäfer-Eckart K, Scheid C, Holtick U, Klein S, Blau IW, Burchert A, Wulf G, Hasenkamp J, Schwerdtfeger R, Kaun S, Junghanss C, Wortmann F, Winter S, Neidlinger H, Theuser C, Beyersmann J, Bornhaeuser M, Schmeller S, and Schetelig J
- Subjects
- Humans, Female, Pregnancy, Adult, Young Adult, Adolescent, Registries, Transplantation, Homologous, Infant, Newborn, Live Birth, Pregnancy Outcome, Transplantation Conditioning methods, Hematopoietic Stem Cell Transplantation
- Abstract
Abstract: Improved long-term survival rates after allogeneic hematopoietic cell transplantation (alloHCT) make family planning for young adult cancer survivors an important topic. However, treatment-related infertility risk poses challenges. To assess pregnancy and birth rates in a contemporary cohort, we conducted a national multicenter study using data from the German Transplant Registry, focusing on adult women aged 18 to 40 years who underwent alloHCT between 2003 and 2018. Of 2654 women who underwent transplantation, 50 women experienced 74 pregnancies, occurring at a median of 4.7 years after transplant. Fifty-seven of these resulted in live births (77%). The annual first birth rate among HCT recipients was 0.45%, which is >6 times lower than in the general population. The probability of a live birth 10 years after HCT was 3.4%. Factors associated with an increased likelihood of pregnancy were younger age at alloHCT, nonmalignant transplant indications, no total body irradiation or a cumulative dose of <8 Gy, and nonmyeloablative/reduced-intensity conditioning. Notably, 72% of pregnancies occurred spontaneously, with assisted reproductive technologies used in the remaining cases. Preterm delivery and low birth weight were more common than in the general population. This study represents the largest data set reporting pregnancies in a cohort of adult female alloHCT recipients. Our findings underscore a meaningful chance of pregnancy in alloHCT recipients. Assisted reproductive technologies techniques are important and funding should be made available. However, the potential for spontaneous pregnancies should not be underestimated, and patients should be informed of the possibility of unexpected pregnancy despite reduced fertility. Further research is warranted to understand the impact of conditioning decisions on fertility preservation., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
- Full Text
- View/download PDF
7. Human Leukocyte Antigen Mismatching and Survival in Contemporary Hematopoietic Cell Transplantation for Hematologic Malignancies.
- Author
-
Arrieta-Bolaños E, Bonneville EF, Crivello P, Robin M, Gedde-Dahl T, Salmenniemi U, Kröger N, Yakoub-Agha I, Crawley C, Choi G, Broers AEC, Forcade E, Carre M, Poiré X, Huynh A, Lenhoff S, Ciceri F, Tholouli E, Schroeder T, Deconinck E, Carlson K, de Wreede LC, Hoogenboom JD, Malard F, Ruggeri A, and Fleischhauer K
- Subjects
- Humans, Middle Aged, Female, Male, Adult, Adolescent, Young Adult, Aged, Child, Cyclophosphamide therapeutic use, Child, Preschool, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation mortality, Hematologic Neoplasms therapy, Hematologic Neoplasms mortality, Hematologic Neoplasms immunology, HLA Antigens immunology, Graft vs Host Disease immunology, Graft vs Host Disease prevention & control, Graft vs Host Disease mortality, Histocompatibility Testing
- Abstract
PURPOSEHuman leukocyte antigen (HLA) mismatching can reduce survival of patients with blood cancer after hematopoietic cell transplantation (HCT). How recent advances in HCT practice, in particular graft-versus-host disease (GVHD) prophylaxis by post-transplantation cyclophosphamide (PTCy), influence HLA risk associations is unknown.PATIENTS AND METHODSThe study included 17,292 unrelated HCTs with 6-locus high-resolution HLA typing, performed mainly for acute leukemia or related myeloid neoplasms between 2016 and 2020, including 1,523 transplants with PTCy. HLA risk associations were evaluated by multivariable Cox regression models, with overall survival (OS) as primary end point.RESULTSOS was lower in HLA mismatched compared with fully matched transplants (hazard ratio [HR], 1.23 [99% CI, 1.14 to 1.33]; P < .001). This was driven by class I HLA-A, HLA-B, HLA-C (HR, 1.29 [99% CI, 1.19 to 1.41]; P < .001) but not class II HLA-DRB1 and HLA-DQB1 (HR, 1.07 [99% CI, 0.93 to 1.23]; P = .19). Class I antigen-level mismatches were associated with worse OS than allele-level mismatches (HR, 1.36 [99% CI, 1.24 to 1.49]; P < .001), as were class I graft-versus-host peptide-binding motif (PBM) mismatches compared with matches (HR, 1.42 [99% CI, 1.28 to 1.59]; P < .001). The use of PTCy improved GVHD, relapse-free survival compared with conventional prophylaxis in HLA-matched transplants (HR, 0.77 [0.66 to 0.9]; P < .001). HLA mismatching increased mortality in PTCy transplants (HR, 1.32 [1.04 to 1.68]; P = .003) similarly as in non-PTCy transplants (interaction P = .43).CONCLUSIONClass I but not class II HLA mismatches, especially at the antigen and PBM level, are associated with inferior survival in contemporary unrelated HCT. These effects are not significantly different between non-PTCy compared with PTCy transplants. Optimized HLA matching should still be considered in modern HCT.
- Published
- 2024
- Full Text
- View/download PDF
8. Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis Aged 70 Years or Older: A Study from the German Registry for Stem Cell Transplantation.
- Author
-
Gagelmann N, Schuh C, Zeiser R, Stelljes M, Bethge W, Wulf G, Teschner D, Klein S, Wagner-Drouet E, Jost E, Dreger P, Flossdorf S, and Kröger N
- Subjects
- Humans, Aged, Male, Female, Germany epidemiology, Retrospective Studies, Transplantation, Homologous, Transplantation Conditioning methods, Aged, 80 and over, Graft vs Host Disease epidemiology, Primary Myelofibrosis mortality, Primary Myelofibrosis therapy, Hematopoietic Stem Cell Transplantation mortality, Registries
- Abstract
Current consensus recommends hematopoietic cell transplantation (HCT) for patients with myelofibrosis with intermediate or high-risk disease and age of less than 70 years. However, a higher chronological age should not be prohibitive for the eligibility decision in general, acknowledging that current life expectancy for the general population aged 70 years is ∼15 years, and current numbers of patients transplanted at 70 years or older is steadily increasing. The following study aimed to evaluate characteristics and outcomes of HCT in 115 myelofibrosis patients aged 70 years or older. This is a retrospective multicenter study, using the German Registry for Stem Cell Transplantation and Cellular Therapy (DRST). Adult myelofibrosis patients were included who received HCT up until 2021. Patients with secondary leukemia were excluded. Main endpoints were HCT demographics over time and outcomes after HCT (including overall survival, relapse incidence, non-relapse mortality, and graft-versus-host disease/relapse-free survival). Numbers of HCT increased over the past decade, with a significant spike since 2019. Comorbidity status of transplanted patients improved over time, while reduced-intensity conditioning was the preferred HCT platform, especially in most recent years. The 3-year overall survival was 55% (95% confidence interval [CI], 44%-65%). The 1-year cumulative incidence of relapse was 7% (95% CI, 3%-13%) and the 1-year cumulative incidence of non-relapse mortality was 22% (95% CI, 14%-31%). The 3-year graft-versus-host disease and relapse-free survival was 37% (95% CI, 27%-47%). Driver mutation genotype (in particular, non-CALR/MPL genotype) appeared to be the only variable that was significantly and independently associated with better survival in multivariable analysis, whereas neither comorbidity index nor dose intensity of pre-transplant conditioning appeared to influence outcome. This study demonstrated feasibility of curative treatment with HCT for myelofibrosis aged 70 or older, with significant increases in HCT numbers and improved fitness of older adults over recent years., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
9. Unrelated donor transplantation with posttransplant cyclophosphamide vs ATG for myelodysplastic neoplasms.
- Author
-
Chalandon Y, Eikema DJ, Moiseev I, Ciceri F, Koster L, Vydra J, Passweg J, Rovira M, Ozcelik T, Gedde-Dahl T, Kröger N, Potter V, Yakoub-Agha I, Rambaldi A, Itälä-Remes M, Tanase A, Onida F, Gurnari C, Scheid C, Drozd-Sokolowska J, Raj K, McLornan DP, and Robin M
- Subjects
- Humans, Middle Aged, Female, Male, Adult, Aged, Young Adult, Transplantation, Homologous, Transplantation Conditioning methods, Adolescent, Treatment Outcome, Cyclophosphamide therapeutic use, Antilymphocyte Serum therapeutic use, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease prevention & control, Graft vs Host Disease etiology, Unrelated Donors, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes mortality
- Abstract
Abstract: It has been reported in prospective randomized trials that antithymocyte globulin (ATG)-based graft-versus-host disease (GVHD) prophylaxis has benefits in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with unrelated donors (UDs). However, the optimal GVHD prophylaxis strategy has been challenged recently by the increasing use of posttransplant cyclophosphamide (PTCY). We report from the European Society for Blood and Marrow Transplantation registry the outcomes of 960 patients with myelodysplastic neoplasms who underwent allo-HSCT from UD with PTCY or ATG as GVHD prophylaxis. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The disease characteristics were similar in both groups. Day 28 neutrophil engraftment was significantly better with ATG (93% vs 85%). Over a median follow-up of 4.4 years, the 5-year OS was 58% with PTCY, and 49% in the ATG group. The 5-year PFS was higher for PTCY at 53% vs 44% for ATG. Grade 2 to 4 acute GVHD incidence was lower when PTCY was used (23%), whereas there was no difference in the incidence of chronic GVHD at 5 years. Multivariable analyses confirmed better OS and PFS with PTCY with a hazard ratio (HR) for ATG of 1.32 (1-1.74) and a better PFS for PTCY with a HR for ATG of 1.33. This study suggests that GVHD prophylaxis using PTCY instead of ATG in this setting remains a valid option. Further prospective randomized studies would be essential to confirm these results., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
10. Gliding motility of the diatom Craspedostauros australis coincides with the intracellular movement of raphid-specific myosins.
- Author
-
Davutoglu MG, Geyer VF, Niese L, Soltwedel JR, Zoccoler ML, Sabatino V, Haase R, Kröger N, Diez S, and Poulsen N
- Subjects
- Phylogeny, Movement, Actins metabolism, Actins genetics, Diatoms metabolism, Diatoms genetics, Diatoms physiology, Myosins metabolism, Myosins genetics
- Abstract
Raphid diatoms are one of the few eukaryotes capable of gliding motility, which is remarkably fast and allows for quasi-instantaneous directional reversals. Besides other mechanistic models, it has been suggested that an actomyosin system provides the force for diatom gliding. However, in vivo data on the dynamics of actin and myosin in diatoms are lacking. In this study, we demonstrate that the raphe-associated actin bundles required for diatom movement do not exhibit a directional turnover of subunits and thus their dynamics do not contribute directly to force generation. By phylogenomic analysis, we identified four raphid diatom-specific myosins in Craspedostauros australis (CaMyo51A-D) and investigated their in vivo localization and dynamics through GFP-tagging. Only CaMyo51B-D but not CaMyo51A exhibited coordinated movement during gliding, consistent with a role in force generation. The characterization of raphid diatom-specific myosins lays the foundation for unraveling the molecular mechanisms that underlie the gliding motility of diatoms., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
11. Comparable Results Between 8 and 12 Gray TBI in Combination With Fludarabine and Post-Transplant Cyclophosphamide in MRD-Negative but Not in MRD-Positive Acute Lymphoblastic Leukemia Patients Transplanted in First Complete Remission.
- Author
-
Steiner N, Massoud R, Richter J, Perekhrestenko T, Gagelmann N, Niederwieser C, Rathje K, Lastovytska I, Schäfersküpper M, Heidenreich S, Rudolph I, Zeck G, Janson D, Wolschke C, Ayuk FA, Klyuchnikov E, and Kröger N
- Abstract
Background: The optimal TBI dose for ALL patients undergoing allogeneic SCT is still not clearly defined., Methods: Single-center retrospective analysis of high-risk ALL patients in CR1 treated with 8 Gy (n = 22) or 12 Gy (n = 50) TBI in combination with fludarabine and PTCy. Median patient age in the 8 Gy TBI cohort was 63 (37-79) and 37 (18-56) in the 12 Gy TBI cohort and median follow-up time was 21 months (range 1-92)., Results: OS and LFS at 2 years after 8 Gy were 65% and 55% versus 74% and 74% after 12 Gy (p = 0.3 and p = 0.2, respectively). CIR and NRM at 2 years were 27% and 14% after 8 Gy versus 4% and 20% after 12 Gy (p = 0.004 and p = 0.4, respectively). MRD-positive (+) patients (n = 26) receiving 12 Gy (n = 19) showed better OS (p = 0.01), LFS (p = 0.009), GRFS, lower CIR (p = 0.02), and similar NRM than did MRD+ patients receiving 8 Gy (n = 7). MRD-negative (-) patients (n = 38) receiving 12 Gy (n = 27) had similar OS, LFS, GRFS, lower CIR, and higher NRM (p = 0.04) than did MRD- patients receiving 8 Gy (n = 11)., Conclusion: Our study demonstrates that 8 Gy TBI in comparison to 12 Gy TBI results in low NRM but a high relapse rate with similar OS, LFS, and GRFS. In MRD+ high-risk ALL patients, allogeneic SCT with 12 Gy TBI leads to improved OS, LFS, GRFS, and a low relapse rate. Prospective studies comparing the different treatment regimens with larger MRD patient cohorts are needed to confirm this data., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
12. A practical guide to therapeutic drug monitoring in busulfan: recommendations from the Pharmacist Committee of the European Society for Blood and Marrow Transplantation (EBMT).
- Author
-
Domingos V, Nezvalova-Henriksen K, Dadkhah A, Moreno-Martinez ME, Ben Hassine K, Pires V, Kröger N, Bauters T, Hassan M, Duncan N, Kalwak K, Ansari M, Langebrake C, and Admiraal R
- Abstract
Busulfan (Bu) is an important component of many conditioning regimens for allogeneic hematopoietic cell transplantation. The therapeutic window of Bu is well characterized, with strong associations between Bu exposure and the clinical outcome in adults (strongest evidence in myelo-ablative setting) and children (all settings). We provide an overview of the literature on Bu as well as a step-by-step guide to the implementation of Bu therapeutic drug monitoring (TDM). The guide covers the clinical, pharmacological, laboratory and administrative aspects of the procedure. Through this document, we aim to support centers in implementing TDM for Bu to further enhance the success rates of HCT and improve patient outcomes. The Pharmacist Committee of the European Society for Blood and Marrow Transplantation (EBMT) encourages all centers to perform TDM for Bu in the aforementioned indications., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
13. Intracellular morphogenesis of diatom silica is guided by local variations in membrane curvature.
- Author
-
Aram L, de Haan D, Varsano N, Gilchrist JB, Heintze C, Rotkopf R, Rechav K, Elad N, Kröger N, and Gal A
- Subjects
- Electron Microscope Tomography, Cell Wall metabolism, Cell Wall ultrastructure, Cryoelectron Microscopy, Diatoms metabolism, Diatoms ultrastructure, Diatoms growth & development, Silicon Dioxide chemistry, Silicon Dioxide metabolism, Cell Membrane metabolism, Morphogenesis
- Abstract
Silica cell-wall formation in diatoms is a showcase for the ability of organisms to control inorganic mineralization. The process of silicification by these unicellular algae is tightly regulated within a membrane-bound organelle, the silica deposition vesicle (SDV). Two opposing scenarios were proposed to explain the tight regulation of this intracellular process: a template-mediated process that relies on preformed scaffolds, or a template-independent self-assembly process. The present work points to a third scenario, where the SDV membrane is a dynamic mold that shapes the forming silica. We use in-cell cryo-electron tomography to visualize the silicification process in situ, in its native-state, and with a nanometer-scale resolution. This reveals that the plasma membrane interacts with the SDV membrane via physical tethering at membrane contact sites, where the curvature of the tethered side of the SDV membrane mirrors the intricate silica topography. We propose that silica growth and morphogenesis result from the biophysical properties of the SDV and plasma membranes., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
14. 6G in medical robotics: development of network allocation strategies for a telerobotic examination system.
- Author
-
Kolb S, Madden A, Kröger N, Mehmeti F, Jurosch F, Bernhard L, Kellerer W, and Wilhelm D
- Abstract
Purpose: Healthcare systems around the world are increasingly facing severe challenges due to problems such as staff shortage, changing demographics and the reliance on an often strongly human-dependent environment. One approach aiming to address these issues is the development of new telemedicine applications. The currently researched network standard 6G promises to deliver many new features which could be beneficial to leverage the full potential of emerging telemedical solutions and overcome the limitations of current network standards., Methods: We developed a telerobotic examination system with a distributed robot control infrastructure to investigate the benefits and challenges of distributed computing scenarios, such as fog computing, in medical applications. We investigate different software configurations for which we characterize the network traffic and computational loads and subsequently establish network allocation strategies for different types of modular application functions (MAFs)., Results: The results indicate a high variability in the usage profiles of these MAFs, both in terms of computational load and networking behavior, which in turn allows the development of allocation strategies for different types of MAFs according to their requirements. Furthermore, the results provide a strong basis for further exploration of distributed computing scenarios in medical robotics., Conclusion: This work lays the foundation for the development of medical robotic applications using 6G network architectures and distributed computing scenarios, such as fog computing. In the future, we plan to investigate the capability to dynamically shift MAFs within the network based on current situational demand, which could help to further optimize the performance of network-based medical applications and play a role in addressing the increasingly critical challenges in healthcare., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
15. Anti-T-lymphocyte globulin (ATLG) compared to post-transplant cyclophosphamide as GvHD prophylaxis in ALL patients undergoing allogeneic stem cell transplantation.
- Author
-
Steiner N, Massoud R, Klyuchnikov E, Gagelmann N, Richter J, Niederwieser C, Rathje K, Urbanowicz T, Kunte A, Engelmann J, Ihne C, Lastovytska I, Lindhauer C, Marquard F, Reichard M, Ryzhkova A, Sabauri R, Schäfersküpper M, Seyedi N, Kalogeropoulos G, Heidenreich S, Rudolph I, Zeck G, Janson D, Wolschke C, Ayuk F, and Kröger N
- Subjects
- Humans, Female, Male, Adult, Retrospective Studies, Middle Aged, Adolescent, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Transplantation Conditioning methods, Transplantation Conditioning adverse effects, Transplantation, Homologous methods, Young Adult, Child, Allografts, Graft vs Host Disease prevention & control, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Antilymphocyte Serum therapeutic use, Antilymphocyte Serum administration & dosage
- Abstract
We retrospectively analyzed high-risk ALL patients in CR1 receiving total body irradiation based conditioning regimen with ATLG (n = 74) or PTCy (n = 73) for GVHD prophylaxis. The 3-year OS and LFS were similar in both groups: 65 and 60% in the ATLG group and 64 and 67% in the PTCy group (p = 0.9 and 0.5, respectively). CIR and NRM rate at three years was 12 and 21% after PTCy and 19 and 20% after ATLG (p = 0.4 and p = 0.9, respectively). Acute GvHD grades II-IV and grades III/IV at 100 days was 46 and 19% after PTCy and 33 and 10% after ATLG (p = 0.08 and p = 0.9, respectively). Chronic GvHD of all grade at two years was higher after PTCy: 55% versus 26% (p < 0.001). Based on the propensity score matching (PSM) analysis, aGvHD grades II-IV was trending higher in the PTCy group compared to the ATLG group (p = 0.07). In contrast to the PSM analysis, on multivariate analysis the receipt of PTCy compared with ATLG was associated with a reduced CIR (p = 0.026). Our retrospective single-center analysis shows a lower incidence of acute and chronic GvHD while displaying similar LFS and OS after ATLG compared to PTCy in TBI based allogeneic stem cell transplantation for high-risk ALL., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
16. Correction: Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the EBMT, ASTCT, CIBMTR, and APBMT.
- Author
-
Sureda A, Carpenter PA, Bacigalupo A, Bhatt VR, de la Fuente J, Ho A, Kean L, Lee JW, Sánchez-Ortega I, Savani BN, Schetelig J, Stadtmauer EA, Takahashi Y, Atsuta Y, Koreth J, Kröger N, Ljungman P, Okamoto S, Popat U, Soiffer R, Stefanski HE, and Kharfan-Dabaja MA
- Published
- 2024
- Full Text
- View/download PDF
17. Comparable relapse incidence after unrelated allogeneic stem cell transplantation with post-transplant cyclophosphamide versus conventional anti-graft versus host disease prophylaxis in patients with acute myeloid leukemia: A study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
- Author
-
Nagler A, Ngoya M, Galimard JE, Labopin M, Blau IW, Kröger N, Gedde-Dahl T, Schroeder T, Burns D, Salmenniemi U, Rambaldi A, Choi G, Peffault de Latour R, Vydra J, Sengeloev H, Eder M, Mielke S, Forcade E, Kulagin A, Ciceri F, and Mohty M
- Subjects
- Humans, Middle Aged, Male, Female, Adult, Incidence, Aged, Adolescent, Recurrence, Young Adult, Transplantation Conditioning methods, Transplantation, Homologous, Retrospective Studies, Immunosuppressive Agents therapeutic use, Graft vs Host Disease prevention & control, Graft vs Host Disease etiology, Graft vs Host Disease epidemiology, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
We compared relapse incidence (RI) post-unrelated transplantation with post-transplant cyclophosphamide (PTCy) versus no PTCy graft-versus-host disease (GVHD) prophylaxis, in 7049 acute myeloid leukemia (AML) patients in remission, 707 with PTCy, and 6342 without (No PTCy). The patients in the PTCy group were younger, 52.7 versus 56.6 years (p < .001). There were more 9/10 donors in the PTCy group, 33.8% versus 16.4% (p < .001), and more received myeloablative conditioning, 61.7% versus 50.2% (p < .001). In the No PTCy group, 87.7% of patients received in vivo T-cell depletion. Neutrophil and platelet engraftment were lower in the PTCy versus No PTCy group, 93.8% and 80.9% versus 97.6% and 92.6% (p < .001). RI was not significantly different in the PTCy versus the No PTCy group, hazard ratio (HR) of 1.11 (95% confidence interval [CI] 0.9-1.37) (p = .31). Acute GVHD grades II-IV and III-IV, were significantly lower in the PTCy versus the No PTCy group, HR of 0.74 (95% CI 0.59-0.92, p = .007) and HR = 0.56 (95% CI 0.38-0.83, p = .004), as were total and extensive chronic GVHD, HRs of 0.5 (95% CI 0.41-0.62, p < .001) and HR = 0.31 (95% CI 0.22-0.42, p < .001). Non-relapse mortality (NRM) was significantly lower with PTCy versus the No PTCy group, HR of 0.67 (95% CI 0.5-0.91, p = .007). GVHD-free, relapse-free survival (GRFS) was higher in the PTCy versus the No PTCy group, HR of 0.69 (95% CI 0.59-0.81, p = .001). Leukemia-free survival (LFS) and overall survival (OS) did not differ between the groups. In summary, we observed comparable RI, OS, and LFS, significantly lower incidences of GVHD and NRM, and significantly higher GRFS in AML patients undergoing unrelated donor-hematopoietic stem cell transplantation with PTCy versus No PTCy GVHD prophylaxis., (© 2024 Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
18. Trends in allogeneic transplantation for favorable risk acute myeloid leukemia in first remission: a longitudinal study of >15 years from the ALWP of the EBMT.
- Author
-
Nagler A, Labopin M, Salmenniemi U, Wu D, Blaise D, Rambaldi A, Reményi P, Forcade E, Socié G, Chevallier P, von dem Borne P, Burns D, Schmid C, Maertens J, Kröger N, Bug G, Aljurf M, Vydra J, Halaburda K, Ciceri F, and Mohty M
- Abstract
We assessed outcomes of allogeneic transplantation (HSCT) in favorable risk AML in CR1 over 3 time periods. 1850 patients were included, 2005 to 2009- 222, 2010 to 2014 -392, and 2015 to 2021-1236; 526 with t (8:21), 625 with inv (16), and 699 with NPM1
mut FLT3WT . Patients transplanted in 2015-2021 were older (p < 0.0001) with more patients ≥60 years of age (p < 0.0001). The most frequent diagnosis in 2015-2021 was NPM1mut FLT3WT vs. t (8:21) in the 2 earlier periods, (p < 0001). Haploidentical transplants (Haplo) increased from 5.9% to 14.5% (p < 0.0001). Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) was more frequent in 2015-2021 vs. the other 2 periods (p < 0.0001). On multivariate analysis, incidence of total chronic GVHD was reduced in HSCTs performed ≥2015 vs. those performed in 2005-2009, hazard ratio (HR) = 0.74 (95% CI 0.56-0.99, p = 0.046) and GVHD-free, relapse-free survival (GRFS) improved for patients transplanted from 2010-2014 vs. those transplanted in 2005-2009, HR = 0.74 (95% CI 0.56-0.98, p = 0.037). Other HSCT outcomes did not differ with no improvement ≥2015. LFS, OS, and GRFS were inferior in patients with t (8:21) with HR = 1.32 (95% CI 1.03-1.68, p = 0.026), HR = 1.38 (95% CI 1.04-1.83, p = 0.027) and HR = 01.25 (95% CI 1.02-1.53, p = 0.035), respectively. In conclusion, this retrospective analysis of HSCT in patients with favorable risk AML, transplanted over 16 years showed an increased number of transplants in patients ≥60 years, from Haplo donors with PTCy. Most importantly, 3-year GRFS improved ≥2010 and total chronic GVHD reduced ≥2015, with no significant change in other HSCT outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
- Full Text
- View/download PDF
19. Isocitrate dehydrogenase (IDH) 1 and 2 mutations predict better outcome in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: a study of the ALWP of the EBMT.
- Author
-
Mohty R, Bazarbachi AH, Labopin M, Esteve J, Kröger N, Cornelissen JJ, Blaise D, Socié G, Maury S, Ganser A, Gedde-Dahl T, von dem Borne P, Bourhis JH, Bulabois CE, Yakoub-Agha I, Pabst C, Nguyen S, Chevallier P, Huynh A, Bazarbachi A, Nagler A, Ciceri F, and Mohty M
- Abstract
Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations have uncertain prognostic implications in AML. We investigate the impact IDH1 and IDH2 mutations in AML patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in first complete remission (CR1). In total, 1515 adult patients were included, 15.91% (n = 241) carried IDH1 mutation (mIDH1), and 26.27% (n = 398) IDH2 mutation (mIDH2) and 57.82% (n = 876) had no-IDH mutation. NPM1 was frequently encountered with IDH1 mutation (no-IDH group, n = 217, 24.8%, mIDH1, n = 103, 42.7%, mIDH2, n = 111, 27.9%, p < 0.0001). At day 180, the cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was significantly lower in mIDH1 and mIDH2 compared to no-IDH groups (Hazard ratio [HR] = 0.66 (95% CI 0.47-0.91), p = 0.011; HR = 0.73 (95% CI 0.56-0.96), p = 0.025, respectively). In the mIDH1 group, overall survival (OS) was improved compared to no-IDH (HR = 0.68 (95% CI 0.48-0.94), p = 0.021), whereas mIDH2 was associated with lower incidence of relapse (HR = 0.49 (95% CI 0.34-0.7), p < 0.001), improved leukemia free survival (LFS) (HR = 0.7 (95% CI 0.55-0.9), p = 0.004) and OS (HR = 0.74 (95% CI 0.56-0.97), p = 0.027). In the subgroup of NPM1 wild type, only IDH2 was associated with improved outcomes. In conclusion, our data suggest that IDH1 and IDH2 mutations are associated with improved outcomes in patients with AML undergoing allo-HCT in CR1., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
20. Proposals for Revised International Working Group-European LeukemiaNet Criteria for Anemia Response in Myelofibrosis.
- Author
-
Tefferi A, Barosi G, Passamonti F, Hernandez-Boluda JC, Bose P, Döhner K, Ellis M, Gangat N, Garcia JS, Gisslinger H, Gotlib J, Guglielmelli P, Gupta V, Harrison CN, Hexner EO, Hobbs GS, Kiladjian JJ, Koschmieder S, Kröger N, Kuykendall AT, Loscocco GG, Mascarenhas JO, Masarova L, Mesa R, Mora B, Odenike O, Oh ST, Pardanani AD, Patel AA, Pemmaraju N, Rambaldi A, Rampal RK, Sirhan S, Szuber N, Talpaz M, Vachhani P, Vannucchi AM, and Barbui T
- Abstract
With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate inter-study comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to i) account for gender-specific differences in determining hemoglobin levels for eligibility criteria, ii) revise definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices, and iii) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks prior to study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs. non-TDA) and graded (major vs. minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment., (Copyright © 2024 American Society of Hematology.)
- Published
- 2024
- Full Text
- View/download PDF
21. Hematopoietic cell transplantation for older acute myeloid leukemia patients in first complete remission: results of a randomized phase III study.
- Author
-
Niederwieser D, Hasenclever D, Berdel WE, Biemond BJ, Al-Ali H, Chalandon Y, Van Gelder M, Junghanß C, Gahrton G, Hänel M, Hehlmann R, Heinicke T, Hochhaus A, Iacobelli S, Kooy RVM, Kröger N, Janssen J, Jentzsch M, Breywisch F, Mohty M, Masouridi-Levrat S, Ossenkoppele G, Passweg J, Pönisch W, Schetelig J, Schliemann C, Schwind S, Stelljes M, Verdonck LF, Vucinic V, Löwenberg B, and Cornelissen J
- Abstract
Given the selection of elderly patients with AML in first complete remission (CR1) the advantage of consolidation with allogeneic hematopoietic cell transplantation (HCT) over chemotherapy is still unclear. Newly diagnosed AML patients in CR1 aged 60-75 years were registered and a donor search initiated. After one consolidation cycle, patients with a matched donor were randomized to HCT with fludarabine/lowdose total body irradiation and cyclosporine/mycophenolate mofetil immunosuppression or conventional non-HCT. Primary outcome was restricted mean leukemia-free survival (RM-LFS) up to five years. Between 2010 and 2017, 245 patients (median age 67 years) were registered at CR1. After one consolidation, 26.9% of patients failed inclusion criteria. Of the 179 (73%) patients still on study, 75.4% had an HLA identical donor. Ten ineligible patients were excluded, and 125 randomized to HCT (n=83) or non-HCT (n=42). The primary outcome RM-LFS up to 5 years was 24.5 months (95%CI:18.9-30.1) in the HCT and 15.6 months (95%CI:10.4-20.8) in the non-HCT arm (p=0.022) due to a decrease in cumulative relapse incidence from 91.1 (95%CI:80.7-100.0) after non-HCT to 37.8 (95%CI:27.2-48.4)% after HCT (p.
- Published
- 2024
- Full Text
- View/download PDF
22. Directionality of HLA-DP permissive mismatches improves risk prediction in HCT for acute leukemia and MDS.
- Author
-
Arrieta-Bolaños E, van der Burg LLJ, Gedde-Dahl T, Robin M, Salmenniemi U, Kröger N, Yakoub-Agha I, Huynh A, Crawley CR, Deconinick E, Bulabois CE, Forcade E, Tholouli E, van der Hem JGK, van Balen P, Hoogenboom JD, de Wreede LC, Malard F, Ruggeri A, and Fleischhauer K
- Abstract
HLA-DP permissive mismatches can be assigned a direction according to their immunopeptidome divergence across core and non-core subsets. Non-core permissive GvH mM show significantly reduced risks of relapse (HR 0.77 [0.63-0.93]; p<0.001) without increased NRM compared to allele-matched pairs., (Copyright © 2024 American Society of Hematology.)
- Published
- 2024
- Full Text
- View/download PDF
23. Impact of busulfan versus treosulfan dose intensity in myelofibrosis undergoing hematopoietic cell transplantation.
- Author
-
Gagelmann N, Schuh C, Flossdorf S, Kunadt D, Stelljes M, Blau IW, Brecht A, Bethge W, Schroeder T, Wulf G, Sala E, Bug G, Fleischhauer K, and Kröger N
- Subjects
- Humans, Middle Aged, Male, Female, Retrospective Studies, Aged, Adult, Antineoplastic Agents, Alkylating therapeutic use, Antineoplastic Agents, Alkylating administration & dosage, Young Adult, Busulfan analogs & derivatives, Busulfan administration & dosage, Busulfan therapeutic use, Hematopoietic Stem Cell Transplantation, Primary Myelofibrosis therapy, Primary Myelofibrosis mortality, Primary Myelofibrosis drug therapy, Transplantation Conditioning methods, Vidarabine analogs & derivatives, Vidarabine administration & dosage, Vidarabine therapeutic use
- Abstract
One key aspect of allogeneic hematopoietic cell transplantation (HCT) is pretransplant conditioning, balancing risk for relapse versus non-relapse mortality. Conditioning regimens with different alkylators at different doses can influence outcome, but data are missing for myelofibrosis, a challenging cohort of patients usually presenting at older age and with comorbidities. We evaluated in a multicenter retrospective study the comparative efficacy and safety of busulfan versus treosulfan in combination with fludarabine for myelofibrosis patients undergoing HCT. This study included 1115 patients (busulfan, n = 902; treosulfan, n = 213) receiving first HCT between 2005 and 2021. Patients were generally balanced for key patient characteristics. Overall survival at 4 years was 62% for the busulfan group versus 58% for the treosulfan group (p = .22). Impact on outcome was dose-dependent. Overall survival was 65% (95% CI, 61%-69%) for reduced intensity busulfan versus 69% (95% CI, 54%-84%) for reduced intensity treosulfan, 53% (95% CI, 44%-63%) for higher intensity busulfan, and 55% (95% CI, 46%-63%) for higher intensity treosulfan. Incidence of relapse was similar across intensity groups. In multivariable analysis, the hazard for death (with reduced intensity busulfan as reference) was 0.88 (95% CI, 0.39-2.01) for reduced intensity treosulfan (p = .77), 1.42 (95% CI, 0.96-2.10) for higher intensity busulfan (0.08), and 1.61 (95% CI, 1.14-2.26) for higher intensity treosulfan (p = .006). In terms of non-relapse mortality, comparison was not significantly different, while the hazard ratio for higher intensity treosulfan was 1.48 (95% CI, 0.98-2.23; p = .06). Here, we showed comparable outcomes and improved survival in myelofibrosis undergoing HCT with reduced intensity busulfan or treosulfan., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
24. Reduced intensity versus myeloablative conditioning for MDS: long-term results of an EBMT phase III study (RICMAC).
- Author
-
Niederwieser C, Iacobelli S, Franke GN, Koster L, van Os M, Platzbecker U, Hübel K, Scheid C, Müller LP, Stelljes M, Morozova E, Passweg J, Onida F, Dreger P, Saccardi R, Ladetto M, Salmenniemi U, Bethge W, Poiré X, Kobbe G, McLornan DP, Robin M, and Kröger N
- Subjects
- Humans, Middle Aged, Adult, Male, Female, Aged, Busulfan therapeutic use, Busulfan administration & dosage, Hematopoietic Stem Cell Transplantation methods, Adolescent, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Vidarabine administration & dosage, Cyclophosphamide therapeutic use, Myeloablative Agonists therapeutic use, Young Adult, Follow-Up Studies, Prospective Studies, Transplantation Conditioning methods, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes mortality
- Abstract
Short-term outcome of myeloablative (MAC) and reduced intensity (RIC) conditioning in the prospective randomized international EBMT RICMAC study in patients with myelodyplastic syndrome (MDS) was comparable but longer follow up is lacking. Patients with MDS aged 18-65 years were randomized to receive MAC (N = 64) with busulfan/cyclophosphamide or RIC (n = 65) with busulfan/fludarabine followed by stem cell transplantation -(HCT) from HLA matched or mismatched donor. After a median follow-up of 6.2 (0.4-12.5) years, 10-year OS and RFS were 54.0% and 43.9% for RIC and 44.4% and 44.2% for MAC (p = 0.15 and p = 0.78), respectively. Since the first report, 6 patients died on NRM, 4 after RIC, and 2 after MAC. Similarly, 8 patients relapsed (4 in each arm), increasing the number of relapsed patients to 28. The second HCT was performed in 18 pts, 8 in the MAC, and 10 in the RIC arm. In a multivariate analysis, ECOG status and chemotherapy prior to HCT were independent risk factors for OS and RFS, ECOG and low cytogenetic risk for NRM and chemotherapy prior to HCT for RI. Patients with low cytogenetic risk had better OS [p = 0.002], RFS [p = 0.02], and NRM (p = 0.015) after RIC as compared to MAC., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
25. How risky is a second allogeneic stem cell transplantation?
- Author
-
Penack O, Abouqateb M, Peczynski C, Boreland W, Kröger N, Zeiser R, Ciceri F, Schroeder T, Dreger P, Passweg J, Schetelig J, Stelljes M, Blau IW, Franke GN, Riesner K, Schoemans H, Moiseev I, and Peric Z
- Subjects
- Humans, Female, Male, Adult, Middle Aged, Young Adult, Adolescent, Aged, Risk Factors, Survival Rate, Neoplasm Recurrence, Local pathology, Recurrence, Graft vs Host Disease etiology, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Hematologic Neoplasms therapy, Hematologic Neoplasms mortality
- Abstract
There is no consensus on second allogeneic stem cell transplantation (alloSCT) indications in patients with hematologic malignancies relapsing after a first alloSCT. In historic publications, a very high non-relapse mortality (NRM) has been described, arguing against performing a second alloSCT. We analysed the outcome of 3356 second alloSCTs performed 2011-21 following a hematologic malignancy relapse. Outcomes at two years after second alloSCT were: NRM 22%, relapse incidence 50%, overall survival 38%, and progression-free survival 28%. Key risk factors for increased NRM were: older age, low performance score, high disease-risk-index, early relapse after the first alloSCT, unrelated/haploidentical donor, and GVHD before second alloSCT. Any type of GVHD after first alloSCT was also important risk factor for acute GVHD and chronic GVHD after second alloSCT. There was a preferential use of a different donor (80%) at second alloSCT from first alloSCT. However, in multivariate analysis, the use of the same alloSCT donor for second alloSCT vs. a different donor was not associated with any of the survival or GVHD endpoints. We show considerably improved outcome as compared to historic reports. These current data support a wider use of second alloSCT and provide risk factors for NRM that need to be considered., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
26. Anti-T-lymphocyte globulin improves GvHD-free and relapse-free survival in myelofibrosis after matched related or unrelated donor transplantation.
- Author
-
Rathje K, Gagelmann N, Salit RB, Schroeder T, Gurnari C, Pagliuca S, Panagiota V, Rautenberg C, Cassinat B, Thol F, Robin M, Oechsler S, Heuser M, Rubio MT, Maciejewski JP, Reinhardt HC, Scott BL, and Kröger N
- Subjects
- Humans, Middle Aged, Female, Male, Adult, Aged, Disease-Free Survival, Transplantation Conditioning methods, Allografts, Young Adult, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Primary Myelofibrosis therapy, Primary Myelofibrosis mortality, Antilymphocyte Serum therapeutic use, Hematopoietic Stem Cell Transplantation methods, Unrelated Donors
- Abstract
Acute and chronic graft-versus-host disease (GvHD) are major complications of allogeneic hematopoietic cell transplantation (alloHCT). In vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG) as part of the conditioning regimen prior to alloHCT is frequently used as GvHD prophylaxis, but data on its role in myelofibrosis is scarce. We took advantage of an international collaborative network to investigate the impact of ATLG in myelofibrosis undergoing first alloHCT. We included 707 patients (n = 469 ATLG and n = 238 non-ATLG prophylaxis). The cumulative incidence of acute GvHD grade II-IV was 30% for the ATLG group vs. 56% for the non-ATLG group (P < 0.001). Acute GvHD grade III-IV occurred in 20% vs. 25%, respectively (P = 0.01). Incidence of mild-to-severe chronic GvHD was 49% vs. 50% (P = 0.52), while ATLG showed significantly lower rates of severe chronic GvHD (7% vs. 18%; P = 0.04). GvHD-free and relapse-free survival (GRFS) at 6 years was 45% for the ATLG group vs. 37% for the non-ATLG group (P = 0.02), driven by significantly improved GRFS of ATLG in matched related and matched unrelated donors. No significant differences in risk for relapse, non-relapse mortality, and overall survival were observed. Multivariable modeling for GRFS showed a 48% reduced risk of GvHD, relapse, or death when using ATLG., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
27. Treatment of newly diagnosed moderate or severe chronic graft-versus-host disease with prednisone and everolimus (PredEver first): a prospective multicenter phase IIA study.
- Author
-
Ayuk F, Wagner-Drouet EM, Wolff D, von Huenerbein N, von Pein UM, Klyuchnikov E, von Harsdorf S, Koenecke C, Sayer H, and Kröger N
- Subjects
- Humans, Middle Aged, Adult, Male, Female, Prospective Studies, Chronic Disease, Aged, Young Adult, Immunosuppressive Agents therapeutic use, Adolescent, Bronchiolitis Obliterans Syndrome, Graft vs Host Disease drug therapy, Everolimus therapeutic use, Everolimus administration & dosage, Prednisone therapeutic use, Prednisone administration & dosage
- Abstract
Although most patients with chronic graft-versus-host disease (cGVHD) show initial response to first-line therapy, long-term clinically meaningful success of first-line treatment remains rare. In a prospective multicentre phase II trial in 6 German centers, patients with newly diagnosed moderate or severe cGVHD received prednisone and everolimus for 12 months followed by a 1-year follow-up period. Primary endpoint was treatment success (TS) at 6 months defined as patient being alive, achieving PR or CR of cGVHD, having no relapse of underlying disease and requiring no secondary treatment for cGVHD. Of the 34 patients evaluable for efficacy, 19 (56%) had TS at 6 months with 22 and 52% of the patients in a CR and PR respectively. Overall 30 patients (88%) had a CR or PR as best response, nearly all responses (29/30) occurring within the first 6 weeks of treatment. The cumulative incidence of treatment failure at 1 year was 63%, corresponding to 37% TS. Predefined safety endpoint (thrombotic microangiopathy, pneumonitis, and avascular necrosis) were not observed in any patient. Addition of everolimus to prednisolone is well tolerated and may improve long-term treatment success. Larger studies are necessary to ascertain the possible role of everolimus in first-line treatment of cGVHD., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
28. Does IPSS-R downstaging before transplantation improve the prognosis of patients with myelodysplastic neoplasms?
- Author
-
Scheid C, Eikema DJ, van Gelder M, Salmenniemi U, Maertens J, Passweg J, Blaise D, Byrne JL, Kröger N, Sockel K, Chevallier P, Bourhis JH, Cornelissen JJ, Sengeloev H, Finke J, Snowden JA, Gedde-Dahl T, Cornillon J, Schanz U, Patel A, Koster L, de Wreede LC, Hayden P, Raj K, Drozd-Sokolowska J, Gurnari C, Onida F, McLornan DP, Robin M, and Yakoub-Agha I
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Retrospective Studies, Prognosis, Adult, Neoplasm Staging, Treatment Outcome, Young Adult, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes pathology, Hematopoietic Stem Cell Transplantation methods
- Abstract
Abstract: In patients with myelodysplastic syndrome (MDS), higher revised International Prognostic Scoring System (IPSS-R) scores at transplant are associated with worse transplant outcome and, thus, lowering IPSS-R scores by therapeutic intervention before transplantation may seem beneficial. However, there is no evidence, to date, to support this approach. In a retrospective analysis, a total of 1482 patients with MDS with sufficient data to calculate IPSS-R score at diagnosis and at time of transplantation were selected from the European Society for Blood and Marrow Transplantation transplant registry and analyzed for transplant outcome in a multivariable Cox model including IPSS-R score at diagnosis, treatment intervention, change in IPSS-R score before transplant, and several patient and transplant variables. Transplant outcome was unaffected by IPSS-R score change in untreated patients and moderately superior in patients treated with chemotherapy with improved IPSS-R score at transplant. Improved IPSS-R score after hypomethylating agents (HMAs) or other therapies showed no beneficial effect. However, when IPSS-R score progressed after chemotherapy, HMAs, or other therapies, transplant outcome was worse than without any prior treatment. Similar results were found when reduction or increase in bone marrow (BM) blasts between diagnosis and transplantation was considered. The results show a limited benefit of IPSS-R score downstaging or reduction of BM blasts after chemotherapy and no benefit for HMAs or other treatments and thus question the role of prior therapy in patients with MDS scheduled for transplantation. The model-based survival estimates should help inform decision-making for both doctors and patients., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
- Published
- 2024
- Full Text
- View/download PDF
29. Allogeneic hematopoietic cell transplantation for older patients with AML with active disease. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).
- Author
-
Maffini E, Labopin M, Kröger N, Finke J, Stelljes M, Schroeder T, Einsele H, Tischer J, Bornhäuser M, Bethge W, Brecht A, Rösler W, Dreger P, Schäfer-Eckart K, Passweg J, Blau IW, Nagler A, Ciceri F, and Mohty M
- Subjects
- Humans, Aged, Male, Female, Retrospective Studies, Transplantation, Homologous methods, Europe, Unrelated Donors, Survival Rate, Disease-Free Survival, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality
- Abstract
Older adults with acute myeloid leukemia (AML) refractory to initial or reinduction chemotherapy have a dismal prognosis if they do not undergo hematopoietic stem-cell transplantation (HCT). However, data assessing HCT outcomes from different donors are scarce. We evaluated results from a retrospective analysis on patients aged ≥70 years, with AML not in remission who received an allogeneic HCT from HLA-matched sibling donor (MSD), HLA-10/10 matched unrelated donor (MUD), or T-cell replete haploidentical (Haplo) donor, from 2010 to 2021, reported to the ALWP-EBMT database. A total of 360 patients (median age 72 years, range 70-79) were included in the analysis. Median follow-up for the entire population was 35.5 months. Donors were MSD (n = 58), 10/10 HLA-MUD (n = 228), and Haplo (n = 74). A total of 213 (59.2%) patients were primary induction failures, while 147 (40.8%) were in first or subsequent relapse. Graft source was peripheral blood in 92% of the patients. Patients transplanted from Haplo donors more frequently received marrow grafts (p < 0.01) and presented the combination female donor to male recipient (p < 0.01). The overall 2-year rates of overall survival (OS) and leukemia-free survival (LFS) were: 62.4% (95% CI 47.2-74.3) and 47.6% (95% CI 33.1-60.8) for MSD, 43% (95% CI 35.8-49.9), and 37.5% (95% CI 30.7-44.4) for MUD, and 25.9% (95% CI 15.8-37.2), and 26.5% (95% CI 16.3-37.8) for recipients of Haplo transplants. The 2-year cumulative incidence of relapse (RI) was slightly lower for Haplo recipients at 29.6% (95% CI 19-40.9), for MUD it was 30.2% (95% CI 23.9-36.7), and for MSD 34.9% (95% CI 22-48.2); counterbalanced by a higher incidence of non-relapse mortality (NRM) of 43.9% (95% CI 31.6-55.6) for Haplo recipients, 32.2% (95% CI 26-33.1) for MUD and 17.5% (95% CI 8.4-29.3) for MSD. Graft-versus-host disease (GVHD-free, relapse-free survival (GRFS) was 35.3% (95% CI 22.3-48.5) for MSD, 29.6% (95% CI 23.2-36.2) for MUD, and 19.2% (95% CI 10.7-29.6) for Haplo patients. In the multivariate model, compared to the referent group of MSD recipients, the risk of NRM was higher among patients transplanted from Haplo donors ([hazard ratio] HR 5.1, 95% CI 2.23-11.61, p < 0.001) and MUD (HR 3.21, 95% CI 1.48-0.6.94, p = 0.003). Furthermore, both Haplo and MUD were associated with inferior OS, (HR 3.6, 95% CI 1.98-0.6.56, p < 0.001, and HR 2.3, 95% CI 1.37-0.3.88, p = 0.002, respectively), and LFS (HR 2.24, 95% CI 1.31-0.3.84, p = 0.003, and HR 1.64, 95% CI 1.04-0.2.60, p = 0.034, respectively). Patients transplanted from Haplo donors were also associated with worse GFRS (HR 1.72, 95% CI 1.07-2.77, p:0.025) compared with MSD patients. Older adult AML patients with active disease transplanted from MSD experienced prolonged OS and LFS compared to 10/10 MUD and Haplo due to lower NRM. Prospective clinical trials are warranted., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
30. Allogeneic hematopoietic stem-cell transplantation for patients with Richter transformation: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.
- Author
-
Guièze R, Eikema DJ, Koster L, Schetelig J, Sengeloev H, Passweg J, Finke J, Arat M, Broers AEC, Stölzel F, Byrne J, Castilla-Llorente C, Dreger P, Eder M, Gedde-Dahl T, Kröger N, Ribera Santasusana JM, Richardson D, Rambaldi A, Yañez L, Van Gelder M, Drozd-Sokolowska J, Raj K, Yakoub-Agha I, Tournilhac O, and McLornan DP
- Subjects
- Humans, Middle Aged, Retrospective Studies, Male, Female, Transplantation, Homologous methods, Transplantation Conditioning methods, Graft vs Host Disease mortality, Adult, Allografts, Hematopoietic Stem Cell Transplantation methods
- Abstract
Management of Richter transformation (RT) is particularly challenging, with survival estimates <1 year. We report on outcomes of 66 RT patients undergoing allogeneic-HCT (allo-HCT) between 2008 and 2018 registered with the EBMT. Median age at allo-HCT was 56.2 years (interquartile range (IQR), 51.3-63.1). Median time from RT to allo-HCT was 6.9 months (IQR, 4.9-11) and 28 (42.4%) were in complete remission (CR). The majority underwent reduced intensity conditioning (66.2%) using peripheral blood derived stem cells. Eighteen (27.3%) patients had a matched sibling donor, 24 (36.4%) a matched unrelated donor and the remaining were mismatched. Median follow-up was 6.6 years; 1- and 3- year overall and progression free survival (PFS) (95% CI) was 65% (54-77) and 39% (27-51) and 53% (41-65) and 29% (18-40), respectively. Patients in CR at time of allo-HCT had significantly better 3-year PFS (39% vs. 21%, p = 0.032). Cumulative incidences of grade II-IV acute graft versus host disease (GVHD) at day +100 was 41% (95% CI 29-53) and chronic GVHD at 3 years was 53% (95% CI 41-65). High rates of non-relapse mortality (NRM) were observed; 38% (95% CI, 26-50) at 3 years. Although potentially curative, approaches to reduce considerable NRM and chronic GVHD rates are required., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
31. Challenges and Pitfalls of Research Designs Involving Magnesium-Based Biomaterials: An Overview.
- Author
-
Hassan N, Krieg T, Kopp A, Bach AD, and Kröger N
- Subjects
- Animals, Humans, Research Design, Materials Testing, Corrosion, Prostheses and Implants, Magnesium chemistry, Biocompatible Materials chemistry
- Abstract
Magnesium-based biomaterials hold remarkable promise for various clinical applications, offering advantages such as reduced stress-shielding and enhanced bone strengthening and vascular remodeling compared to traditional materials. However, ensuring the quality of preclinical research is crucial for the development of these implants. To achieve implant success, an understanding of the cellular responses post-implantation, proper model selection, and good study design are crucial. There are several challenges to reaching a safe and effective translation of laboratory findings into clinical practice. The utilization of Mg-based biomedical devices eliminates the need for biomaterial removal surgery post-healing and mitigates adverse effects associated with permanent biomaterial implantation. However, the high corrosion rate of Mg-based implants poses challenges such as unexpected degradation, structural failure, hydrogen evolution, alkalization, and cytotoxicity. The biocompatibility and degradability of materials based on magnesium have been studied by many researchers in vitro; however, evaluations addressing the impact of the material in vivo still need to be improved. Several animal models, including rats, rabbits, dogs, and pigs, have been explored to assess the potential of magnesium-based materials. Moreover, strategies such as alloying and coating have been identified to enhance the degradation rate of magnesium-based materials in vivo to transform these challenges into opportunities. This review aims to explore the utilization of Mg implants across various biomedical applications within cellular (in vitro) and animal (in vivo) models.
- Published
- 2024
- Full Text
- View/download PDF
32. The impact of MICB mismatches in unrelated haematopoietic stem cell transplantation.
- Author
-
Amann EM, Gowdavally S, Tsamadou C, Platzbecker U, Sala E, Wagner-Drouet E, Valerius T, Kröger N, Wulf G, Einsele H, Thurner L, Schaefer-Eckart K, Freitag S, Casper J, Dürholt M, Kaufmann M, Hertenstein B, Klein S, Ringhoffer M, Frank S, Saal T, Schmid-Möglich A, Neuchel C, Schrezenmeier H, Mytilineos J, and Fürst D
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Unrelated Donors, Adolescent, Transplantation, Homologous methods, Polymorphism, Genetic, Aged, Young Adult, HLA Antigens genetics, HLA Antigens immunology, Linkage Disequilibrium, Alleles, Child, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease genetics, Histocompatibility Testing methods, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class I immunology
- Abstract
MICA polymorphisms have been associated with increased incidence of acute GvHD and adverse outcome in allogeneic haematopoietic stem cell transplantation (HSCT). MICB is another expressed member of MHC class I-related chain genes and its impact on HSCT outcome is yet to be fully defined. We typed a large cohort of patients and donors for MICB polymorphisms and investigated the impact of MICB matching on outcome after unrelated HSCT. 69.2% of the patients were 10/10 human leukocyte antigen (HLA) matched and 30.8% were 9/10 HLA matched. MICB typing was performed using a short amplicon-based NGS typing assay on the Illumina MiSeq platform. Differences in proteins were considered as mismatches. MICA polymorphisms were identified as possible confounder and were therefore included as parameter in the multivariate analyses. Due to the strong linkage disequilibrium with the classical HLA-genes, sub-stratification for HLA matching status was necessary, and no effect of MICB mismatches was seen in the 10/10 HLA matched group when compared to the MICB matched cases. However, in the 9/10 HLA matched group, MICB mismatched cases showed significantly worse disease free survival (DFS), GvHD and relapse free survival (GRFS) compared to the MICB matched cases (DFS: HR 1.24, p = 0.011; GRFS: HR 1.26, p = 0.002). MICA mismatches had no impact on any outcome parameter. According to our findings, effects previously attributed to MICA differences may have been confounded by MICB polymorphisms. We show that MICB differences contribute a small but relevant effect in 9/10 HLA-matched transplantations, which in turn highlights the possible usefulness of MICB typing in donor selection among similarly suitable 9/10 matched donors, especially when HLA-B mismatches have to be accepted., (© 2024 The Author(s). HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)
- Published
- 2024
- Full Text
- View/download PDF
33. Risk factors for Nocardia infection among allogeneic hematopoietic cell transplant recipients: A case-control study of the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation.
- Author
-
De Greef J, Averbuch D, Tondeur L, Duréault A, Zuckerman T, Roussel X, Robin C, Xhaard A, Pagliuca S, Beguin Y, Botella-Garcia C, Khanna N, Le Bourgeois A, Van Praet J, Ho A, Kröger N, Ducastelle Leprêtre S, Roos-Weil D, Aljurf M, Blijlevens N, Blau IW, Carlson K, Collin M, Ganser A, Villate A, Lakner J, Martin S, Nagler A, Ram R, Torrent A, Stamouli M, Mikulska M, Gil L, Wendel L, Tridello G, Knelange N, de la Camara R, Lortholary O, Fontanet A, Styczynski J, Maertens J, Coussement J, and Lebeaux D
- Subjects
- Humans, Male, Female, Case-Control Studies, Risk Factors, Middle Aged, Retrospective Studies, Adult, Transplantation, Homologous adverse effects, Aged, Transplant Recipients statistics & numerical data, Nocardia isolation & purification, Antibiotic Prophylaxis, Nocardia Infections epidemiology, Hematopoietic Stem Cell Transplantation adverse effects, Trimethoprim, Sulfamethoxazole Drug Combination therapeutic use
- Abstract
Objectives: Nocardiosis is a rare but life-threatening infection after hematopoietic cell transplantation (HCT). We aimed at identifying risk factors for nocardiosis after allogeneic HCT and clarifying the effect of trimethoprim-sulfamethoxazole prophylaxis on its occurrence., Methods: We performed a retrospective multicenter case-control study of patients diagnosed with nocardiosis after allogeneic HCT between January 2000 and December 2018. For each case, two controls were matched by center, transplant date, and age group. Multivariable analysis was conducted using conditional logistic regression to identify potential risk factors for nocardiosis. Kaplan-Meier survival curves of cases and controls were compared using log-rank tests., Results: Sixty-four cases and 128 controls were included. Nocardiosis occurred at a median of 9 months after allogeneic HCT (interquartile range: 5-18). After adjustment for potential confounders in a multivariable model, Nocardia infection was associated with tacrolimus use (adjusted odds ratio [aOR] 9.9, 95 % confidence interval [95 % CI]: 1.6-62.7), lymphocyte count < 500/µL (aOR 8.9, 95 % CI: 2.3-34.7), male sex (aOR 8.1, 95 % CI: 2.1-31.5), recent use of systemic corticosteroids (aOR 7.9, 95 % CI: 2.2-28.2), and recent CMV infection (aOR 4.3, 95 % CI: 1.2-15.9). Conversely, use of trimethoprim-sulfamethoxazole prophylaxis was associated with a significantly decreased risk of nocardiosis (aOR 0.2, 95 % CI: 0.1-0.8). HCT recipients who developed nocardiosis had a significantly decreased survival, as compared with controls (12-month survival: 58 % and 90 %, respectively; p < 0.0001)., Conclusions: We identified six factors independently associated with the occurrence of nocardiosis among allogeneic HCT recipients. In particular, trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
34. Axicabtagene Ciloleucel versus Tisagenlecleucel for Relapsed or Refractory Large B Cell Lymphoma: A Systematic Review and Meta-Analysis.
- Author
-
Gagelmann N, Bishop M, Ayuk F, Bethge W, Glass B, Sureda A, Pasquini MC, and Kröger N
- Subjects
- Humans, Immunotherapy, Adoptive methods, Antigens, CD19 immunology, Antigens, CD19 therapeutic use, Receptors, Antigen, T-Cell therapeutic use, Cytokine Release Syndrome, Treatment Outcome, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse mortality, Biological Products therapeutic use, Biological Products administration & dosage
- Abstract
Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor T cell (CAR-T) therapies approved for relapsed/refractory aggressive large B cell lymphoma (LBCL). Significant costs and complex manufacturing underscore the importance of evidence-based counseling regarding the outcomes of these treatments. With the aim of examining the efficacy and safety of axi-cel versus tisa-cel in patients with relapsed/refractory aggressive LBCL, we performed a systematic literature search of comparative studies evaluating outcomes in relapsed/refractory aggressive LBCL after treatment with axi-cel or tisa-cel. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for response, progression-free survival (PFS), overall survival (OS), cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematotoxicity. Meta-analysis and meta-regression were used to generate summary statistics. A total of 2372 participants were included in the 8 studies in our analysis. The dropout rate between apheresis and infusion was 13% for axi-cel versus 18% for tisa-cel, and the median time from apheresis to infusion was 32 days versus 45 days. Axi-cel showed higher odds for a complete response (OR, 1.65; P < .001) and was associated with higher odds for PFS at 1 year after infusion (OR, .60; P < .001). OS appeared to be improved with axi-cel (OR, .84; 95% CI, .68 to 1.02; P = .08), whereas the cumulative incidence of nonrelapse mortality (NRM) was 11.5% for axi-cel versus 3.7% for tisa-cel (P = .002). The main predictors for survival were lactate dehydrogenase level, Eastern Cooperative Oncology Group Performance Status, and response to bridging, and axi-cel maintained superior efficacy even in elderly patients. In terms of safety, axi-cel was associated with significantly higher odds of any-grade CRS (OR, 3.23; P < .001), but not of grade ≥3 CRS (P = .92). Axi-cel was associated with significantly higher odds of severe ICANS grade ≥3 (OR, 4.03; P < .001). In terms of hematotoxicity, axi-cel was significantly associated with higher odds of severe neutropenia at 1 month after infusion (OR, 2.06; P = .003). As a result, axi-cel was associated with significantly greater resource utilization, including prolonged hospital stay, more frequent intensive care admission, and use of agents such as tocilizumab for toxicity management. We provide strong evidence of the greater efficacy of axi-cel versus tisa-cel in relapsed/refractory aggressive LBCL. The higher toxicity and NRM seen with axi-cel might not counterbalance the overall results, highlighting the need for timely intervention and careful selection of patients, balancing resource utilization and clinical benefit., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
35. Celebrating the registration of 9.000 patients treated with CAR T cells in the EBMT registry: Collection of real-world data in the context of hematopoietic cellular therapies.
- Author
-
Chabannon C, Ruggeri A, Montoto S, van Biezen A, van der Werf S, Markslag A, Sanchez-Ortega I, Camara R, Ljungman P, Mohty M, Kröger N, Sureda A, McGrath E, Bonini C, and Kuball J
- Subjects
- Humans, Europe, Hematopoietic Stem Cell Transplantation, Receptors, Chimeric Antigen therapeutic use, Registries, Immunotherapy, Adoptive methods
- Abstract
The European society for Blood and Marrow Transplantation (EBMT) has a long-standing interest in the evaluation of hematopoietic cell transplantation. More than three decades ago, its members established a continental registry. Today, more than 700,000 patients have been registered, and information has been gathered on more than 800,000 transplants. This huge amount of information has allowed conducting multiple retrospective studies, evaluating changes in practices over time and for different categories of diseases, benchmarking outcome across EBMT affiliated centers, and increasingly serves to build synthetic comparators to evaluate the introduction of therapeutic innovations in the field of hematology. CAR-T cells therapies draw on human and technical resources that are also used to deliver HCT; they elicit side effects that require the implementation of risk mitigation plans; they are living drugs that persist in the body of the recipient and thus deserve prolonged follow-up; the introduction of CAR-T cells in the pharmacopeia is likely to significantly impact on the practice of BMT; for all these reasons and even before the first approvals of CAR-T Cells in Europe, EBMT engaged in a project aiming at complementing the EBMT Registry with a Cellular Therapy Form, with the objective to register CAR-T cells treated patients and collect information on their short-, middle- and long-term outcome. The goal is to provide EBMT investigators with a tool for primary analyses of the collected information and to support secondary use of data transferred at the individual level to Marketing Authorization Holders and other interested parties, to fulfill their obligations to health authorities and further evaluate the actual medical values of CAR-T Cells in different contexts and indications. The EBMT Registry received a positive opinion from the European Medicines agency in 2019, and five years later contains information on more than 9.000 treated patients. This article describes the journey to start this new activity, lessons to be drawn in view of improving the collection of real-world data, and what existing information tells us in terms of patient access., Competing Interests: Declaration of competing interest AvB, SvdW, AM, ISO, EMG are or have been permanent and paid employees with EBMT. CC, AR, SM, RdlC, PL, MM, NK, AS, CB & JK volunteer part of their professional time to contribute to EBMT missions and tasks, in different and temporary positions. In their different capacities, all co-authors have interacted with Pharma companies (including Novartis, Kite/Gilead, BMS, Janssen) that develop and commercialize CAR-T Cells and other advanced therapies to establish the European CAR-T Cells Registry described in this manuscript, and launch PASS and PAES. Interactions with Pharma companies as well as with other public or private, not-for profit or for-profit organizations is ongoing in the context of the GoCART Coalition. JK received funding from Novartis, Miltenyi Biotech, is a cofounder of Gadeta as well as shareholder of floow-up companies of Gadeta such as Century Therapeutics and Adeta., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
36. Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the EBMT, ASTCT, CIBMTR, and APBMT.
- Author
-
Sureda A, Carpenter PA, Bacigalupo A, Bhatt VR, de la Fuente J, Ho A, Kean L, Lee JW, Sánchez-Ortega I, Savani BN, Schetelig J, Stadtmauer EA, Takahashi Y, Atsuta Y, Koreth J, Kröger N, Ljungman P, Okamoto S, Popat U, Soiffer R, Stefanski HE, and Kharfan-Dabaja MA
- Subjects
- Humans, Allografts, Male, Female, Adult, Transplantation Chimera, Transplantation, Homologous methods, Hematopoietic Stem Cell Transplantation methods, Graft Rejection
- Abstract
Despite emergence of novel therapies to treat hematologic malignancies, allogeneic hematopoietic cell transplantation (allo-HCT) remains an essential treatment modality capable of curing these diseases. Allo-HCT has been also shown to be curative in benign hematologic disorders such as aplastic anemia, sickle cell disease, and thalassemia, among others. Recently, the American Society for Transplantation and Cellular Therapy (ASTCT) published standardized definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism. To attempt broader international consensus, a panel of adult and pediatric physician transplant experts was assembled from European Society for Blood and Marrow Transplantation (EBMT), ASTCT, the Center for International Blood and Marrow Transplant Research (CIBMTR), and Asia-Pacific Blood and Marrow Transplantation (APBMT). Consensus was defined as ≥70% of voting members strongly agreeing or somewhat agreeing with a definition. With few exceptions, there was a consensus to endorse the prior ASTCT definitions. Importantly, we revised existing EBMT and CIBMTR data collection forms to align with these harmonized definitions that will facilitate research and international collaboration among transplant researchers and across transplant registries., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
37. Haploidentical stem cell donor choice for patients with acute myeloid leukemia: a study from the ALWP of the EBMT.
- Author
-
Sanz J, Labopin M, Blaise D, Raiola AM, Busca A, Vydra J, Tischer J, Chevallier P, Bramanti S, Fanin R, Socié G, Forcade E, Kröger N, Koc Y, Itäla-Remes M, Zecca M, Nagler A, Brissot E, Spyridonidis A, Bazarbachi A, Giebel S, Piemontese S, Mohty M, and Ciceri F
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Adolescent, Aged, Child, Young Adult, Retrospective Studies, Transplantation, Haploidentical methods, Tissue Donors, Donor Selection, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control
- Abstract
Abstract: There is a paucity of information to guide the selection of the most suitable donor in haploidentical (Haplo) hematopoietic stem cell transplantation (HSCT). For this reason, from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we conducted a retrospective analysis to evaluate the impact of Haplo donor characteristics on outcomes in patients with acute myeloid leukemia (AML) who received graft-versus-host disease prophylaxis with posttransplant cyclophosphamide (PTCy). The primary end point was graft-versus-host disease (GVHD)-free and relapse-free survival (GRFS). Overall, 2200 patients were included. The median age of donors was 37 years (range, 8-71); 820 (37%) were females, including 458 (21%) who were used for male recipients. In addition, 1631 donors (74%) donated peripheral blood (PB). Multivariable analysis identified certain donor-related risk factors with a detrimental impact on transplant outcomes. The use of PB, older donors' ages (>37 years), and female donors to male recipients negatively affected GRFS. Donor's age and female donor-to-male recipient combination also affected nonrelapse mortality, leukemia-free survival, and overall survival. In conclusion, donor-related variables significantly influence outcomes in patients with AML after Haplo-HSCT with PTCy. When possible, younger donors and male donors for male recipients should be prioritized. The use of bone marrow can additionally prevent GVHD., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
38. Development and Validation of a Prediction Model of Outcome After B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Multiple Myeloma.
- Author
-
Gagelmann N, Dima D, Merz M, Hashmi H, Ahmed N, Tovar N, Oliver-Caldés A, Stölzel F, Rathje K, Fischer L, Born P, Schäfer L, Albici AM, Schub N, Kfir-Erenfeld S, Assayag M, Asherie N, Wulf GG, Kharboutli S, Müller F, Shune L, Davis JA, Anwer F, Vucinic V, Platzbecker U, Ayuk F, Kröger N, Khouri J, Gurnari C, McGuirk J, Stepensky P, Abdallah AO, and Fernández de Larrea C
- Subjects
- Humans, Middle Aged, Male, Retrospective Studies, Female, Aged, United States, Adult, Receptors, Chimeric Antigen immunology, Europe, Treatment Outcome, Neoplasm Recurrence, Local therapy, Multiple Myeloma therapy, Multiple Myeloma mortality, Multiple Myeloma immunology, Immunotherapy, Adoptive methods, B-Cell Maturation Antigen immunology
- Abstract
Purpose: Although chimeric antigen receptor T therapy (CAR-T) cells are an established therapy for relapsed/refractory multiple myeloma (RRMM), there are no established models predicting outcome to identify patients who may benefit the most from CAR-T., Patients and Methods: This is an international retrospective observational study including patients with RRMM infused with currently available commercial or academically produced anti-B-cell maturation antigen (BCMA) CAR-T. We describe characteristics and outcomes in Europe (n = 136) and the United States (n = 133). Independent predictors of relapse/progression built a simple prediction model (Myeloma CAR-T Relapse [MyCARe] model) in the training cohort (Europe), which was externally validated (US cohort) and tested within patient- and treatment-specific subgroups., Results: The overall response rate was 87% and comparable between both cohorts, and complete responses were seen in 48% (Europe) and 49% (the United States). The median time to relapse was 5 months, and early relapse <5 months from infusion showed poor survival across cohorts, with the 12-month overall survival of 30% (Europe) and 14% (the United States). The presence of extramedullary disease or plasma cell leukemia, lenalidomide-refractoriness, high-risk cytogenetics, and increased ferritin at the time of lymphodepletion were independent predictors of early relapse or progression. Each factor received one point, forming the three-tiered MyCARe model: scores 0-1 (low risk), scores 2-3 (intermediate risk), and a score of 4 (high risk). The MyCARe model was significantly associated with distinct 5-month incidence of relapse/progression ( P < .001): 7% for low-risk, 27% for intermediate-risk, and 53% for high-risk groups. The model was validated in the US cohort and maintained prognostic utility for response, survival, and outcomes across subgroups., Conclusion: Outcomes of patients with RRMM after CAR-T are comparable between Europe and the United States. The MyCARe model may facilitate optimal timing of CAR-T cells in patient-specific subgroups.
- Published
- 2024
- Full Text
- View/download PDF
39. Continuously improving outcome over time after second allogeneic stem cell transplantation in relapsed acute myeloid leukemia: an EBMT registry analysis of 1540 patients.
- Author
-
Schmälter AK, Ngoya M, Galimard JE, Bazarbachi A, Finke J, Kröger N, Bornhäuser M, Stelljes M, Stölzel F, Tischer J, Schroeder T, Dreger P, Blau IW, Savani B, Giebel S, Esteve J, Nagler A, Schmid C, Ciceri F, and Mohty M
- Subjects
- Humans, Middle Aged, Male, Female, Adult, Aged, Young Adult, Adolescent, Transplantation, Homologous, Recurrence, Transplantation Conditioning methods, Treatment Outcome, Graft vs Host Disease etiology, Graft vs Host Disease epidemiology, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Registries, Hematopoietic Stem Cell Transplantation methods
- Abstract
Second allogeneic stem cell transplantation (alloSCT2) is among the most effective treatments for acute myeloid leukemia (AML) relapse after first alloSCT (alloSCT1). Long-term EBMT registry data were used to provide large scale, up-to-date outcome results and to identify factors for improved outcome. Among 1540 recipients of alloSCT2, increasing age, better disease control and performance status before alloSCT2, more use of alternative donors and higher conditioning intensity represented important trends over time. Between the first (2000-2004) and last (2015-2019) period, two-year overall and leukemia-free survival (OS/LFS) increased considerably (OS: 22.5-35%, LFS: 14.5-24.5%). Cumulative relapse incidence (RI) decreased from 64% to 50.7%, whereas graft-versus-host disease and non-relapse mortality (NRM) remained unchanged. In multivariable analysis, later period of alloSCT2 was associated with improved OS/LFS (HR = 0.47/0.53) and reduced RI (HR = 0.44). Beyond, remission duration, disease stage and patient performance score were factors for OS, LFS, RI, and NRM. Myeloablative conditioning for alloSCT2 decreased RI without increasing NRM, leading to improved OS/LFS. Haploidentical or unrelated donors and older age were associated with higher NRM and inferior OS. In summary, outcome after alloSCT2 has continuously improved over the last two decades despite increasing patient age. The identified factors provide clues for the optimized implementation of alloSCT2., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
40. ATG or post-transplant cyclophosphamide to prevent GVHD in matched unrelated stem cell transplantation?
- Author
-
Penack O, Abouqateb M, Peczynski C, Boreland W, Kröger N, Stelljes M, Gedde-Dahl T, Blau IW, Schroeder T, Salmenniemi U, Kulagin A, Peffault de Latour R, Mielke S, Zeiser R, Moiseev I, Schoemans H, Koenecke C, and Peric Z
- Subjects
- Humans, Male, Middle Aged, Female, Adult, Unrelated Donors, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Immunosuppressive Agents therapeutic use, Transplantation, Homologous, Aged, Young Adult, Transplantation Conditioning methods, Adolescent, Survival Rate, Follow-Up Studies, Retrospective Studies, Cyclophosphamide therapeutic use, Graft vs Host Disease prevention & control, Graft vs Host Disease etiology, Antilymphocyte Serum therapeutic use, Hematologic Neoplasms therapy, Hematologic Neoplasms mortality
- Abstract
There is a high risk of GVHD and non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) from unrelated donors. Prophylaxis with rabbit anti-thymocyte globulin (rATG) is standard in Europe but post-transplantation Cyclophosphamide (PTCy) is an emerging alternative. We analyzed outcomes of rATG (n = 7725) vs. PTCy (n = 1039) prophylaxis in adult patients with hematologic malignancies undergoing peripheral blood alloSCT from 10/10 antigen-matched unrelated donors (MUD) between January 2018 and June 2021 in the EBMT database. The provided P-values and hazard ratios (HR) are derived from multivariate analysis. Two years after alloSCT, NRM in the PTCy group was 12.1% vs. 16.4% in the rATG group; p = 0.016; HR 0.72. Relapse was less frequent after PTCy vs. rATG (22.8% vs. 26.6%; p = 0.046; HR 0.87). Overall survival after PTCy was higher (73.1% vs. 65.9%; p = 0.001, HR 0.82). Progression free survival was better after PTCy vs. rATG (64.9% vs. 57.2%; p < 0.001, HR 0.83). The incidence of chronic GVHD was lower after PTCy (28.4% vs. rATG 31.4%; p = 0.012; HR 0.77), whereas the incidence and severity of acute GVHD were not significantly different. GVHD-free relapse-free survival was significantly higher in the PTCy arm compared to the rATG arm (2 y incidence: 51% vs. 45%; HR: 0.86 [95% CI 0.75-0.99], p = 0.035). In the absence of evidence from randomized controlled trials, our findings support a preference for the use of PTCy in adult recipients of peripheral blood alloSCTs from MUD., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
41. Autologous-allogeneic versus autologous tandem stem cell transplantation and maintenance therapy with thalidomide for multiple myeloma patients under 60 years of age: a prospective, phase II study.
- Author
-
Kröger N, Wulf G, Hegenbart U, Burchert A, Stelljes M, Gagelmann N, Brecht A, Kaufmann M, Müller L, Ganser A, Wolf D, Bethge W, Bornhäuser M, Kiehl M, Wagner EM, Schmid C, Reinhardt HC, Kobbe G, Salwender H, Heinicke T, Kropff M, Heinzelmann M, Ayuk F, Trümper L, Neubauer A, Völp A, Kluychnikov E, Schönland S, and Wolschke C
- Subjects
- Humans, Middle Aged, Male, Female, Adult, Prospective Studies, Transplantation, Homologous, Treatment Outcome, Multiple Myeloma therapy, Multiple Myeloma mortality, Multiple Myeloma diagnosis, Thalidomide administration & dosage, Thalidomide therapeutic use, Hematopoietic Stem Cell Transplantation methods, Transplantation, Autologous, Maintenance Chemotherapy
- Abstract
The role of autologous-allogeneic tandem stem cell transplantation (alloTSCT) followed by maintenance as upfront treatment for multiple myeloma is controversial. Between 2008 and 2014 a total of 217 multiple myeloma patients with a median age of 51 years were included by 20 German centers within an open-label, parallel-group, multicenter clinical trial to compare alloTSCT to autologous tandem transplantation (autoTSCT) followed by 2 years of maintenance therapy with thalidomide (100 mg/day) in both arms with respect to relapse/progression-free survival (PFS) and other relevant outcomes. A total of 178 patients underwent a second transplant (132 allogeneic, 46 autologous). PFS at 4 years after the second transplant was 47% (95% CI: 38-55%) for alloTSCT and 35% (95% CI: 21-49%) for autoTSCT (P=0.26). This difference increased to 22% at 8 years (P=0.10). The cumulative incidences of non-relapse mortality and of relapse at 4 years were 13% (95% CI: 8-20%) and 2% (95% CI: 0.3-2%) (P=0.044) and 40% (95% CI: 33-50%) and 63% (95% CI: 50-79%) (P=0.04) for alloTSCT and autoTSCT, respectively. The difference for relapse/progression increased to 33% (alloTSCT: 44%, autoTSCT: 77%) at a median follow-up of 82 months (P=0.002). Four-year overall survival was 66% (95% CI: 57-73%) for alloTSCT and 66% (95% CI: 50-78%) for autoTSCT (P=0.91) and 8-year overall survival was 52% and 50% (P=0.87), respectively. In conclusion, alloTSCT followed by thalidomide maintenance reduced the rate of recurrence or progression during a follow-up period of up to 10 years but failed to improve PFS significantly. This study was registered with ClinicalTrials.gov (NCT00777998).
- Published
- 2024
- Full Text
- View/download PDF
42. Hematopoietic cell transplantation (HCT) in MDS patients of older age.
- Author
-
Niederwieser C and Kröger N
- Subjects
- Humans, Aged, Age Factors, Treatment Outcome, Geriatric Assessment methods, Aged, 80 and over, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation adverse effects, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes diagnosis, Transplantation Conditioning methods
- Abstract
Hematopoietic cell transplantation (HCT) has evolved to an essential treatment in younger and more recently in elderly patients with myelodysplastic syndrome (MDS), the age group with the highest incidence. Less intense conditioning regimens and improvements in supportive therapy have reduced considerably transplant related mortality and in the same time increased the access to this curative treatment. Timing of HCT in the course of the disease assumes a crucial role. Detection of disease progression, geriatric assessment, comorbidity evaluation, and identification of transplant-specific risks are becoming increasingly important in this context. Novel statistical methods, molecular biomarkers, and quantification of tumor burden pre- and post-HCT will play an essential role in years to come. More effective and less toxic treatments to reduce the tumor burden before and/or after HCT are expected to improve the outcome. In this review article we discuss the current views and what we can expect.
- Published
- 2024
- Full Text
- View/download PDF
43. Improvements in Posttransplant Outcomes Over Two Decades in Older Patients with Acute Myeloid Leukemia in the EBMT ALWP Study.
- Author
-
Bazarbachi A, Labopin M, Moukalled N, Kröger N, Rautenberg C, Schetelig J, Finke J, Blau IW, Blaise D, Stelljes M, Eder M, Platzbecker U, Dreger P, Bethge W, Tischer J, Burns D, Sengeloev H, Brissot E, Giebel S, Nagler A, Ciceri F, and Mohty M
- Subjects
- Humans, Aged, Female, Male, Aged, 80 and over, Treatment Outcome, Transplantation, Homologous, Follow-Up Studies, Graft vs Host Disease etiology, Graft vs Host Disease epidemiology, Transplantation Conditioning methods, Remission Induction, Retrospective Studies, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Hematopoietic Stem Cell Transplantation methods, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Purpose: Acute myeloid leukemia (AML) is a disease of older patients. Progress in allogeneic hematopoietic cell transplantation (allo-HCT) allowed the delivery of allo-HCT to older patients. We assessed changes over time in transplant characteristics and outcomes in patients with AML ages 65 years and above., Patients and Methods: We identified 7,215 patients with AML (median age 68 years, range 65-80) allografted between 2000 and 2021 in first complete remission (CR1; 64%), second or subsequent remission (CR2+; 14%), or active disease (22%)., Results: Median follow-up was 40 months. The 3-year cumulative relapse incidence (RI) gradually and significantly decreased from 37% to 31%, then to 30% (P = 0.001) over the three time periods (2000-2009; 2010-2014; 2015-2021), whereas nonrelapse mortality (NRM) decreased from 31% and 31% to 27% (P = 0.003). The 3-year leukemia-free survival (LFS) and overall survival (OS) gradually and significantly improved from 32% to 38%, and then to 44% (P = 0.001) and from 37% to 42%, and then to 49% (P = 0.001), respectively. In multivariate analysis, significant improvement in the RI, LFS, and OS were noted after 2015, whereas NRM was not significantly affected. This improvement was observed regardless of disease status at transplant., Conclusions: In older patients with AML, we observed an impressive improvement over time in posttransplant outcomes, mostly attributed to decreased RI rather than decreased NRM, and regardless of disease status at transplant. These large-scale, real-world data can serve as a benchmark for future studies in this setting and indicate that the opportunity for transplant for the elderly should be mandatory and no longer an option., (©2024 American Association for Cancer Research.)
- Published
- 2024
- Full Text
- View/download PDF
44. Splenic irradiation for myelofibrosis prior to hematopoietic cell transplantation: A global collaborative analysis.
- Author
-
Gagelmann N, Hobbs GS, Campodonico E, Helbig G, Novak P, Schroeder T, Schneider A, Rautenberg C, Reinhardt HC, Bosques L, Heuser M, Panagiota V, Thol F, Gurnari C, Maciejewski JP, Ciceri F, Rathje K, Robin M, Pagliuca S, Rubio MT, Rocha V, Funke V, Hamerschlak N, Salit R, Scott BL, Duarte F, Mitrus I, Czerw T, Greco R, and Kröger N
- Subjects
- Humans, Spleen, Splenomegaly etiology, Splenomegaly radiotherapy, Recurrence, Transplantation Conditioning methods, Primary Myelofibrosis radiotherapy, Primary Myelofibrosis complications, Hematopoietic Stem Cell Transplantation methods, Thrombocytopenia complications, Graft vs Host Disease etiology
- Abstract
Splenomegaly is the clinical hallmark of myelofibrosis. Splenomegaly at the time of allogeneic hematopoietic cell transplantation (HCT) is associated with graft failure and poor graft function. Strategies to reduce spleen size before HCT especially after failure to Janus kinase (JAK) inhibition represent unmet clinical needs in the field. Here, we leveraged a global collaboration to investigate the safety and efficacy of splenic irradiation as part of the HCT platform for patients with myelofibrosis. We included 59 patients, receiving irradiation within a median of 2 weeks (range, 0.9-12 weeks) before HCT. Overall, the median spleen size prior to irradiation was 23 cm (range, 14-35). Splenic irradiation resulted in a significant and rapid spleen size reduction in 97% of patients (57/59), with a median decrease of 5.0 cm (95% confidence interval, 4.1-6.3 cm). The most frequent adverse event was thrombocytopenia, with no correlation between irradiation dose and hematological toxicities. The 3-year overall survival was 62% (95% CI, 48%-76%) and 1-year non-relapse mortality was 26% (95% CI, 14%-38%). Independent predictors for survival were severe thrombocytopenia and anemia before irradiation, transplant-specific risk score, higher-intensity conditioning, and present portal vein thrombosis. When using a propensity score matching adjusted for common confounders, splenic irradiation was associated with significantly reduced relapse (p = .01), showing a 3-year incidence of 12% for splenic irradiation versus 29% for patients with immediate HCT and 38% for patients receiving splenectomy. In conclusion, splenic irradiation immediately before HCT is a reasonable approach in patients experiencing JAK inhibition failure and is associated with a low incidence of relapse., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)
- Published
- 2024
- Full Text
- View/download PDF
45. Methodological challenges in the development of endpoints for myelofibrosis clinical trials.
- Author
-
Barosi G, Tefferi A, Gangat N, Szuber N, Rambaldi A, Odenike O, Kröger N, Gagelmann N, Talpaz M, Kantarjian H, and Gale RP
- Subjects
- Humans, Endpoint Determination, Janus Kinase Inhibitors therapeutic use, Quality of Life, Clinical Trials as Topic, Primary Myelofibrosis drug therapy
- Abstract
Myelofibrosis is a myeloid neoplasm characterised by the presence of JAK2, CALR, or MPL mutations (with a 90% mutation frequency) and trilineage myeloid proliferation with prominent megakaryocyte atypia. People with myelofibrosis have a lower survival rate and poorer quality of life than healthy individuals. Therapy for myelofibrosis uses Janus kinase inhibitors, which reduce splenomegaly and alleviate symptoms. Regulatory approvals for Janus kinase inhibitors have focused on this dual endpoint. In this Viewpoint, we discuss the validity of using spleen reduction as a surrogate endpoint for the disease-modifying activity of candidate drugs for myelofibrosis. We suggest alternative endpoints addressing unmet patient needs, including progression-free survival and overall survival. Moreover, we highlight the importance of selecting a core set of crucial outcomes with which we can individualise clinical decision making and standardise reporting of clinical trials results. We propose selecting patient-reported outcomes and anaemia response. We also suggest integrating economic considerations in the process of evaluating new drugs for myelofibrosis., Competing Interests: Declaration of interests NGan has received honoraria for an educational event from OncoLive. AR has received honoraria for lectures or presentations from Novartis, Amgen, Pfizer, Astellas, Jazz, Janssen, Incyte, Kite–Gilead, Roche, and Omeros; has received support for attending meetings or travel from Novartis, Amgen, Pfizer, Astellas, Jazz, Janssen, Incyte, Kite–Gilead, Roche, and Omeros; and has participated on a data safety monitoring board or advisory board for Novartis, Amgen, Pfizer, Astellas, Jazz, Janssen, Incyte, Kite–Gilead, Roche, and Omeros. OO has received consulting fees from Servier, Rigel, AbbVie, Incyte; and has received fees from Threadwell Therapeutics for their service on a data safety monitoring board for an ongoing clinical trial. NK has received honoraria for lectures from Kite–Gilead, Jazz, MSD, Neovii Biotech, Alexion, MSD, Taked, Novartis, Riemser, Pfizer, and BMS; and has received research support from Neovii, Riemser, Novartis, and DKMS. NGag has received consulting fees from MorphoSys and Stemline. MT has received consulting or advisory fees from Novartis, Bristol Myers Squibb–Celgene, Kyowa Kirin International, Imago Pharma, SDP Oncology, Sierra Oncology, and GlaxoSmithKline; and has received research funding from Bristol Myers Squibb–Celgene and Arcus Biosciences. HK has received honoraria for participation on an advisory board and consulting from AbbVie, Amgen, Ascentage, Amphista, Astellas, Biologix, Curis, Ipsen Biopharmaceuticals, KAHR Medical, Labcorp, Novartis, Pfizer, Shenzhen Target Rx, Stemline, Takeda; and has received research grants from AbbVie, Amgen, Ascentage, BMS, Daiichi Sankyo, Immunogen, Jazz, and Novartis. RPG is a consultant for Antengene; Medical Director of FFF Enterprises; a speaker for Janssen Pharma and Hengrui Pharma; on the board of directors for the Russian Foundation for Cancer Research Support; and on the scientific advisory board for StemRad. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
46. Impact of post-transplant cyclophosphamide (PTCy)-based prophylaxis in matched sibling donor allogeneic haematopoietic cell transplantation for patients with myelodysplastic syndrome: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.
- Author
-
Salas MQ, Eikema DJ, Koster L, Maertens J, Passweg J, Finke J, Broers AEC, Koc Y, Kröger N, Ozkurt ZN, Pascual-Cascon MJ, Platzbecker U, Van Gorkom G, Schroeder T, López-Lorenzo JL, Martino M, Chiusolo P, Kaufmann M, Onida F, Gurnari C, Scheid C, Drozd-Sokolowska J, Raj K, Robin M, and McLornan DP
- Subjects
- Humans, Retrospective Studies, Siblings, Cyclophosphamide therapeutic use, Cyclophosphamide pharmacology, Unrelated Donors, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Myelodysplastic Syndromes complications, Neoplasms complications
- Abstract
We retrospectively compared outcomes of 404 MDS patients undergoing 1st matched sibling donor allo-HCT receiving either PTCy-based (n = 66) or other "conventional prophylaxis" (n = 338; mostly calcineurin inhibitor + methotrexate or MMF). Baseline characteristics were balanced, except for higher use of myeloablative regimens in the PTCy group (52.3% vs. 38.2%, p = 0.047). Incidences of neutrophil (Day +28: 89% vs. 97%, p = 0.011) and platelet (Day +100: 89% vs. 97%, p < 0.001) engraftment were lower for PTCy-based. Day +100 cumulative incidences of grade II-IV and III-IV aGVHD, and 5-year CI of extensive cGVHD were 32%, 18% and 18% for PTCy-based and 25% (p = 0.3), 13% (p = 0.4) and 31% (p = 0.09) for the conventional cohort. Five-year OS (51% vs. 52%, p = 0.6) and GRFS (33% vs. 25%, p = 0.6) were similar between groups. Patients receiving PTCy had a trend to a lower cumulative incidence of relapse (20% vs. 33%, p = 0.06), not confirmed on multivariable analysis (p = 0.3). Although higher NRM rates were observed in patients receiving PTCy (32% vs. 21%, p = 0.02) on univariate analysis, this was not confirmed on multivariate analysis (HR 1.46, p = 0.18), and there was no resultant effect on OS (HR 1.20, p = 0.5). Based on these data, PTCy prophylaxis appears to be an attractive option for patients with MDS undergoing MSD allo-HCT., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
- Full Text
- View/download PDF
47. Graft-versus-host disease and impact on relapse in myelofibrosis undergoing hematopoietic stem cell transplantation.
- Author
-
Oechsler S, Gagelmann N, Wolschke C, Janson D, Badbaran A, Klyuchnikov E, Massoud R, Rathje K, Richter J, Schäfersküpper M, Niederwieser C, Kunte A, Heidenreich S, Ayuk F, and Kröger N
- Subjects
- Humans, Neoplasm Recurrence, Local drug therapy, Antilymphocyte Serum therapeutic use, Primary Myelofibrosis complications, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology
- Abstract
Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative treatment for myelofibrosis (MF). Relapse occurs in 10-30% and remains a major factor for dismal outcomes. Previous work suggested that graft-versus-host disease (GVHD) might be associated with risk of relapse. This study included 341 patients undergoing their first (n = 308) or second (n = 33) alloHSCT. Anti-T-lymphocyte or antithymocyte globulin was used for GVHD prophylaxis in almost all patients. Median time to neutrophile and platelet engraftment was 13 days and 19 days, respectively. The cumulative incidence of acute GVHD grade II-IV was 41% (median, 31 days; range, 7-112). Grade III-IV acute GVHD was observed in 22%. The cumulative incidence of chronic GVHD was 61%. Liver was affected in 23% of acute GVHD cases and 46% of chronic GVHD cases. Severe acute GVHD was associated with high non-relapse mortality. The development of acute GVHD grade II and moderate GVHD was an independent factor for reduced risk for relapse after transplantation without increased risk for non-relapse mortality, while especially acute GVHD grade IV was associated with high non-relapse mortality. Last, we identified that ongoing response to ruxolitinib, accelerated-phase MF at time of transplantation and splenectomy prior to transplantation were independent predictors for relapse., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
48. Allogeneic Hematopoietic Cell Transplantation in Advanced Systemic Mastocytosis: A retrospective analysis of the DRST and GREM registries.
- Author
-
Lübke J, Christen D, Schwaab J, Kaiser A, Naumann N, Shoumariyeh K, Jentzsch M, Sockel K, Schaffrath J, Ayuk FA, Stelljes M, Hilgendorf I, Sala E, Kaivers J, Schönland S, Wittke C, Hertenstein B, Radsak M, Kaiser U, Brückl V, Kröger N, Brümmendorf TH, Hofmann WK, Klein S, Jost E, Reiter A, and Panse J
- Subjects
- Humans, Retrospective Studies, Mastocytosis, Systemic genetics, Leukemia, Mast-Cell, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute
- Abstract
We identified 71 patients with AdvSM (aggressive SM [ASM], SM with an associated hematologic neoplasm [SM-AHN, e.g., acute myeloid leukemia, SM-AML], mast cell leukemia [MCL]) in two national registries (DRST/GREM) who received an allogeneic hematopoietic cell transplantation (alloHCT) performed in Germany from 1999-2021. Median overall survival (OS) of ASM/SM-AHN (n = 30, 45%), SM-AML (n = 28, 39%) and MCL ± AHN (n = 13, 19%) was 9.0, 3.3 and 0.9 years (P = 0.007). Improved median OS was associated with response of SM (17/41, 41%; HR 0.4 [0.2-0.9], P = 0.035) and/or of AHN (26/43, 60%, HR 0.3 [0.1-0.7], P = 0.004) prior to alloHCT. Adverse predictors for OS included absence of KIT D816V (10/61, 16%, HR 2.9 [1.2-6.5], P < 0.001) and a complex karyotype (9/60, 15%, HR 4.2 [1.8-10.0], P = 0.016). HLA-match, conditioning type or transplantation at centers reporting above-average alloHCTs (≥7) had no impact on OS. Taking into account competing events at years 1, 3 and 5, relapse-related mortality and non-relapse mortality rate were 15%/23%, 20%/30% and 23%/35%, respectively. Irrespective of subtype, subsequent treatment response was achieved in 13/30 (43%) patients and was highest on midostaurin/avapritinib (7/9, 78%). We conclude that outcome of alloHCT in AdvSM is more affected by disease phenotype and treatment response prior to transplant than by transplant characteristics., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
49. PTCy versus ATG as graft-versus-host disease prophylaxis in mismatched unrelated stem cell transplantation.
- Author
-
Penack O, Abouqateb M, Peczynski C, Boreland W, Gülbas Z, Gedde-Dahl T, Castilla-Llorente C, Kröger N, Eder M, Rambaldi A, Bonifazi F, Blau IW, Stelljes M, Dreger P, Moiseev I, Schoemans H, Koenecke C, and Peric Z
- Subjects
- Adult, Humans, Neoplasm Recurrence, Local drug therapy, Cyclophosphamide therapeutic use, Antilymphocyte Serum therapeutic use, Unrelated Donors, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control
- Abstract
There is an increased risk of GVHD and of non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) when mismatched unrelated donors (MMUD) are used. In Europe, it is standard practice to use rabbit anti-thymocyte globulin (rATG) to reduce the high NRM and GVHD risks after MMUD alloSCT. As an alternative to rATG, post-transplantation Cyclophosphamide (PTCy) is in increasing clinical use. It is currently impossible to give general recommendations regarding preference for one method over another since comparative evidence from larger data sets is lacking. To improve the evidence base, we analyzed the outcome of rATG vs. PTCy prophylaxis in adult patients with hematologic malignancies undergoing first peripheral blood alloSCT from MMUD (9/10 antigen match) between Jan 2018 and June 2021 in the database of the European Society for Blood and Marrow Transplantation (EBMT). We performed multivariate analyses using the Cox proportional-hazards regression model. We included 2123 patients in the final analyses (PTCy, n = 583; rATG, n = 1540). p values and hazard ratios (HR) presented here are multivariate outcomes. Two years after alloSCT we found a lower NRM in the PTCy group of 18% vs. 24.9% in the rATG group; p = 0.028, HR 0.74. Overall survival in the PTCy cohort was higher with 65.7% vs. 55.7% in the rATG cohort; p < 0.001, HR 0.77. Progression-free survival was also better in the PTCy patients with 59.1% vs. 48.8% when using rATG; p = 0.001, 0.78. The incidences of chronic GVHD and acute GVHD were not significantly different between the groups. We found significantly lower NRM as well as higher survival in recipients of peripheral blood alloSCTs from MMUD receiving PTCy as compared to rATG. The results of the current analysis suggest an added value of PTCy as GVHD prophylaxis in MMUD alloSCT., (© 2024. The Author(s).)
- Published
- 2024
- Full Text
- View/download PDF
50. Mechanism of branching morphogenesis inspired by diatom silica formation.
- Author
-
Babenko I, Kröger N, and Friedrich BM
- Subjects
- Morphogenesis, Silicon Dioxide chemistry, Diatoms chemistry
- Abstract
The silica-based cell walls of diatoms are prime examples of genetically controlled, species-specific mineral architectures. The physical principles underlying morphogenesis of their hierarchically structured silica patterns are not understood, yet such insight could indicate novel routes toward synthesizing functional inorganic materials. Recent advances in imaging nascent diatom silica allow rationalizing possible mechanisms of their pattern formation. Here, we combine theory and experiments on the model diatom Thalassiosira pseudonana to put forward a minimal model of branched rib patterns-a fundamental feature of the silica cell wall. We quantitatively recapitulate the time course of rib pattern morphogenesis by accounting for silica biochemistry with autocatalytic formation of diffusible silica precursors followed by conversion into solid silica. We propose that silica deposition releases an inhibitor that slows down up-stream precursor conversion, thereby implementing a self-replicating reaction-diffusion system different from a classical Turing mechanism. The proposed mechanism highlights the role of geometrical cues for guided self-organization, rationalizing the instructive role for the single initial pattern seed known as the primary silicification site. The mechanism of branching morphogenesis that we characterize here is possibly generic and may apply also in other biological systems., Competing Interests: Competing interests statement:The authors declare no competing interest.
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.