31 results on '"Halter, J."'
Search Results
2. Schlauchmagenbildung in der Behandlung der morbiden Adipositas
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Buesing, M., Utech, M., Halter, J., Riege, R., Saada, G., and Knapp, A.
- Abstract
Zusammenfassung: Hintergrund: Die chirurgische Therapie der morbiden Adipositas gewinnt auch in Deutschland zunehmend an Bedeutung. Neben Standardoperationen wie der RNY-Bypass-Anlage steht mit der Schlauchmagenbildung (Sleeve-Gastrektomie) ein noch relativ neues Verfahren zur Verfügung, dessen Effekt überwiegend auf die Magenverkleinerung (Restriktion) zurückgeführt wird, daneben scheinen aber neurohumorale und vermutlich noch weitere unbekannte Faktoren von Bedeutung zu sein. Die bisherigen Ergebnisse der Schlauchmagenbildung sind vielversprechend, müssen sich aber hinsichtlich Komplikationsraten, Gewichtsreduktion und der konsekutiven Rückbildung adipositasassoziierter Begleiterkrankungen mit etablierten Verfahren, insbesondere dem RNY-Bypass, messen lassen. Patienten und Methoden: Zwischen 05/08–11/09 erfolgte bei 200 Patienten (136 Frauen, 64 Männer) mit einer Adipositas II–III eine Schlauchmagenbildung als operatives Primärverfahren. Das Patientenalter lag im Mittel bei 43 Jahren (21–72 Jahre), der BMI bei 47,9 kg/m
2 (35,5–75,3 kg/m2 ). Bei 70 Patienten (35%) bestand eine diabetische Stoffwechsellage, bei 96 Patienten (48%) eine arterielle Hypertonie. In 14 Fällen wurde der Eingriff transvaginal assistiert (Hybrid-NOTES) geplant. Ergebnisse: Die intendierte laparoskopische Sleeve-Gastrektomie war in allen Fällen möglich. Postoperative Komplikationen ergaben sich bei 3 Patienten (1,5%) in Form von Leckagen der Nahtreihe in 2 Fällen (1%) und in einem Fall mit einer Nachblutung aus der Bauchdecke und nachfolgender Lungenembolie (0,5%). Die genannten Komplikationen verliefen in 2 Fällen (1%) tödlich. Der durchschnittliche stationäre Aufenthalt bei den 197 Patienten ohne Komplikationen lag bei 3,5 Tagen (2–9 Tage). Die transvaginale Technik erlaubte die Reduzierung der erforderlichen Bauchdeckentrokare um 1–2, in allen Fällen konnte das Magenresektat transvaginal geborgen werden. Komplikationen ergaben sich von Seiten des vaginalen Zugangs nicht. Bereits nach einem Beobachtungszeitraum von 3 Monaten konnten von 70 Diabetikern 45 Patienten (64%) ihre Diabetesmedikation komplett einstellen, der Bedarf an Antihypertensiva reduzierte sich ebenfalls. Die bisher erreichte Gewichtsreduktion nach 3, 6 und 12 Monaten ergibt durchschnittliche Werte von 27,3%, 41% bzw. 58% (EWL). Schlussfolgerung: Die Schlauchmagenbildung scheint ein effektives und sicheres chirurgisches Verfahren zur Therapie der morbiden Adipositas zu sein. Innerhalb des ersten Jahres nach der Operation kommt es zu einer sehr raschen Gewichtsreduktion, adipositasassoziierte Begleiterkrankungen wie Diabetes mellitus und arterielle Hypertonie bilden sich zurück. Die transvaginale Hybrid-NOTES-Technik ist bereits jetzt durchführbar, erfordert allerdings bislang weitere Zugänge im Bereich der Bauchdecke. Die Langzeitergebnisse im Hinblick auf eine anhaltende Gewichtsreduktion und adipositasassoziierter Begleiterkrankungen bleiben abzuwarten. Die bisherigen Ergebnisse sind damit denen des RNY-Bypass vergleichbar.- Published
- 2024
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3. P29 - DYSLIPIDEMIA AFTER INTENSIVE IMMUNOSUPPRESSIVE THERAPY VERSUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN APLASTIC ANEMIA: A SINGLE-CENTER EXPERIENCE
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Holeczek, C, Halter, J, Arranto, C, Schaedelin, S, Mathew, R, Leuppi-Taegtmeyer, A, Burkard, T, Betz, M, Passweg, J, and Drexler, B
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- 2023
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4. Nosocomial human parainfluenza virus type 3 outbreak in immunocompromised patients, and possible lessons from the SARS-CoV-2 pandemic
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Gürtler, N., primary, Osthoff, M., additional, Egli, A., additional, Halter, J., additional, Khanna, N., additional, Tschudin-Sutter, S., additional, and Bassetti, S., additional
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- 2022
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5. Clinical prediction model for prognosis in kidney transplant recipients (KIDMO): study protocol
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Schwab, Simon, Sidler, Daniel, Haidar, Fadi, Kuhn, Christian, Schaub, Stefan, Koller, Michael, Mellac, Katell, Stürzinger, Ueli, Tischhauser, Bruno, Binet, Isabelle, Golshayan, Déla, Müller, Thomas, Elmer, Andreas, Franscini, Nicola, Krügel, Nathalie, Fehr, Thomas, Immer, Franz, Swisstransplant Kidney Working Group (STAN), Swiss Transplant Cohort Study, Amico, P., Folie, P., Gannagé, M., Matter, M., Nilsson, J., Peloso, A., de Rougemont, O., Schnyder, A., Spartà, G., Storni, F., Villard, J., Wirth-Müller, U., Wolff, T., Aubert, J.D., Banz, V., Beckmann, S., Beldi, G., Berger, C., Berishvili, E., Berzigotti, A., Bochud, P.Y., Branca, S., Bucher, H., Catana, E., Cairoli, A., Chalandon, Y., De Geest, S., De Seigneux, S., Dickenmann, M., Dreifuss, J.L., Duchosal, M., Ferrari-Lacraz, S., Garzoni, C., Goossens, N., Halter, J., Heim, D., Hess, C., Hillinger, S., Hirsch, H.H., Hirt, P., Hoessly, L., Hofbauer, G., Huynh-Do, U., Laesser, B., Lamoth, F., Lehmann, R., Leichtle, A., Manuel, O., Marti, H.P., Martinelli, M., McLin, V., Merçay, A., Mettler, K., Mueller, N.J., Müller-Arndt, U., Müllhaupt, B., Nägeli, M., Oldani, G., Pascual, M., Passweg, J., Pazeller, R., Posfay-Barbe, K., Rick, J., Rosselet, A., Rossi, S., Rothlin, S., Ruschitzka, F., Schachtner, T., Scherrer, A., Schuurmans, M., Sengstag, T., Simonetta, F., Stampf, S., Steiger, J., Stirnimann, G., Van Delden, C., Venetz, J.P., Vionnet, J., Wick, M., Wilhelm, M., and Yerly, P.
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Microbiology (medical) ,Immunology ,Immunology and Allergy ,610 Medicine & health ,Estimated glomerular filtration rate ,Graft survival ,Kidney transplantation ,Patient-reported health status ,Prediction model ,Prognosis ,Prognostic model ,Quality of life ,Risk calculator ,Risk score ,eGFR ,610 Medizin und Gesundheit - Abstract
Background Many potential prognostic factors for predicting kidney transplantation outcomes have been identified. However, in Switzerland, no widely accepted prognostic model or risk score for transplantation outcomes is being routinely used in clinical practice yet. We aim to develop three prediction models for the prognosis of graft survival, quality of life, and graft function following transplantation in Switzerland. Methods The clinical kidney prediction models (KIDMO) are developed with data from a national multi-center cohort study (Swiss Transplant Cohort Study; STCS) and the Swiss Organ Allocation System (SOAS). The primary outcome is the kidney graft survival (with death of recipient as competing risk); the secondary outcomes are the quality of life (patient-reported health status) at 12 months and estimated glomerular filtration rate (eGFR) slope. Organ donor, transplantation, and recipient-related clinical information will be used as predictors at the time of organ allocation. We will use a Fine & Gray subdistribution model and linear mixed-effects models for the primary and the two secondary outcomes, respectively. Model optimism, calibration, discrimination, and heterogeneity between transplant centres will be assessed using bootstrapping, internal-external cross-validation, and methods from meta-analysis. Discussion Thorough evaluation of the existing risk scores for the kidney graft survival or patient-reported outcomes has been lacking in the Swiss transplant setting. In order to be useful in clinical practice, a prognostic score needs to be valid, reliable, clinically relevant, and preferably integrated into the decision-making process to improve long-term patient outcomes and support informed decisions for clinicians and their patients. The state-of-the-art methodology by taking into account competing risks and variable selection using expert knowledge is applied to data from a nationwide prospective multi-center cohort study. Ideally, healthcare providers together with patients can predetermine the risk they are willing to accept from a deceased-donor kidney, with graft survival, quality of life, and graft function estimates available for their consideration. Study registration Open Science Framework ID: z6mvj
- Published
- 2023
6. Donation type and the effect of pre-transplant donor specific antibodies – Data from the Swiss Transplant Cohort Study
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de Rougemont, Olivier, Deng, Yun, Frischknecht, Lukas, Wehmeier, Caroline, Villard, Jean, Ferrari-Lacraz, Sylvie, Golshayan, Déla, Gannagé, Monique, Binet, Isabelle, Wirthmüller, Urs, Sidler, Daniel, Schachtner, Thomas, Schaub, Stefan, Nilsson, Jakob, Swiss Transplant Cohort Study, Amico, P., Axel, A., Aubert, J.D., Banz, V., Sonja, B., Beldi, G., Berger, C., Berishvili, E., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carrel, T., Catana, E., Chalandon, Y., De Geest, S., De Rougemont, O., Dickenmann, M., Dreifuss, J.L., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Franscini, N., Garzoni, C., Soccal, P.G., Gaudet, C., Golshayan, D., Goossens, N., Hadaya, K., Halter, J., Heim, D., Hess, C., Hillinger, S., Hirsch, H., Hirt, P., Hofbauer, G., Huynh-Do, U., Immer, F., Koller, M., Laager, M., Laesser, B., Lehmann, R., Leichtle, A., Lovis, C., Manuel, O., Marti, H.P., Martin, P.Y., Martinelli, M., McLin, V., Mellac, K., Mercay, A., Mettler, K., Mueller, N., Müller, A., Müller, T., Müller-Arndt, U., Müllhaupt, B., Nägeli, M., Oldani, G., Pascual, M., Posfay-Barbe, K., Rick, J., Rosselet, A., Rossi, S., Rothlin, S., Ruschitzka, F., Schanz, U., Schaub, S., Schnyder, A., Schuurmans, M., Sengstag, T., Simonetta, F., Staufer, K., Stampf, S., Steiger, J., Stirniman, G., Stürzinger, U., Van Delden, C., Venetz, J.P., Villard, J., Vionnet, J., Wick, M., Wilhlem, M., and Yerly, P.
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Humans ,Antibodies ,Blood Grouping and Crossmatching ,Cohort Studies ,Living Donors ,Switzerland ,ABMR ,DBD ,DCD ,donor specific antibodies ,graft loss ,kidney transplantation ,living donation ,virtual cross-match ,Immunology ,Immunology and Allergy ,610 Medicine & health ,610 Medizin und Gesundheit - Abstract
IntroductionThe type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome.MethodsWe investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants.ResultsThere was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (DiscussionOur results suggest that the negative impact of pre-transplant DSA on graft outcome could be similar between all donation types. This suggests that immunological risk assessment could be performed in a similar way regardless of the type of donor kidney transplantation.
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- 2023
7. Cohort profile: The Swiss Transplant Cohort Study (STCS): A nationwide longitudinal cohort study of all solid organ recipients in Switzerland
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Stampf, Susanne, Mueller, Nicolas J., van Delden, Christian, Pascual, Manuel, Manuel, Oriol, Banz, Vanessa, Binet, Isabelle, De Geest, Sabina, Bochud, Pierre-Yves, Leichtle, Alexander, Schaub, Stefan, Steiger, Jürg, Koller, Michael, Swiss Transplant Cohort Study, members of the Swiss Transplant Cohort Study, Swiss Transplant Cohort Study, members of the Swiss Transplant Cohort Study, Amico, P., Axel, A., Aubert, J.D., Banz, V., Sonja, B., Beldi, G., Berger, C., Berishvili, E., Berzigotti, A., Binet, I., Bochud, P.Y., Branca, S., Bucher, H., Carrel, T., Catana, E., Chalandon, Y., Geest, S., Rougemont, O., Seigneux, S., Dickenmann, M., Dreifuss, J.L., Duchosal, M., Fehr, T., Ferrari-Lacraz, S., Franscini, N., Garzoni, C., Soccal, P.G., Gaudet, C., Golshayan, D., Goossens, N., Hadaya, K., Halter, J., Heim, D., Hess, C., Hillinger, S., Hirsch, H., Hirt, P., Hofbauer, G., Huynh-Do, U., Immer, F., Koller, M., Laager, M., Laesser, B., Lehmann, R., Leichtle, A., Lovis, C., Manuel, O., Marti, H.P., Martin, P.Y., Martinelli, M., McLin, V., Mellac, K., Merçay, A., Mettler, K., Mueller, N., Müller, A., Müller-Arndt, U., Müllhaupt, B., Nägeli, M., Oldani, G., Pascual, M., Posfay-Barbe, K., Rick, J., Rosselet, A., Rossi, S., Rothlin, S., Ruschitzka, F., Schachtner, T., Schanz, U., Schaub, S., Schnyder, A., Schuurmans, M., Sengstag, T., Simonetta, F., Stampf, S., Steiger, J., Stirniman, G., Stürzinger, U., Delden, C.V., Venetz, J.P., Villard, J., Vionnet, J., Wick, M., Wilhlem, M., Yerly, P., University of Zurich, and Stampf, Susanne
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PREVENTIVE STRATEGIES ,10255 Clinic for Thoracic Surgery ,Epidemiology ,CYTOMEGALOVIRUS ,INVASIVE PULMONARY ASPERGILLOSIS ,610 Medicine & health ,2700 General Medicine ,030230 surgery ,infectious diseases ,10234 Clinic for Infectious Diseases ,immunology ,03 medical and health sciences ,epidemiology ,oncology ,transplant medicine ,Medicine, General & Internal ,0302 clinical medicine ,General & Internal Medicine ,INFECTION ,Humans ,Longitudinal Studies ,Prospective Studies ,PROTECTION ,POLYMORPHISMS ,OUTCOMES ,Science & Technology ,General Medicine ,Transplant Recipients ,3. Good health ,surgical procedures, operative ,REJECTION ,10032 Clinic for Oncology and Hematology ,10209 Clinic for Cardiology ,RISK-FACTORS ,030211 gastroenterology & hepatology ,Life Sciences & Biomedicine ,Switzerland - Abstract
PurposeThe Swiss Transplant Cohort Study (STCS) is a prospective multicentre cohort study which started to actively enrol study participants in May 2008. It takes advantage of combining data from all transplant programmes in one unique system to perform comprehensive nationwide reporting and to promote translational and clinical post-transplant outcome research in the framework of Swiss transplantation medicine.ParticipantsOver 5500 solid organ transplant recipients have been enrolled in all six Swiss transplant centres by end of 2019, around three-quarter of them for kidney and liver transplants. Ninety-three per cent of all transplanted recipients have consented to study participation, almost all of them (99%) contributed to bio-sampling. The STCS genomic data set includes around 3000 patients.Findings to dateDetailed clinical and laboratory data in high granularity as well as patient-reported outcomes from transplant recipients and activities in Switzerland are available in the last decade. Interdisciplinary contributions in diverse fields of transplantation medicine such as infectious diseases, genomics, oncology, immunology and psychosocial science have resulted in approximately 70 scientific papers getting published in peer-review journals so far.Future plansThe STCS will deepen its efforts in personalised medicine and digital epidemiology, and will also focus on allocation research and the use of causal inference methods to make complex matters in transplant medicine more understandable and transparent.
- Published
- 2021
8. Revealing the unseen: next generation sequencing for early detection of drug-resistant cytomegalovirus variants upon letermovir prophylaxis failure.
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Nägele K, Bättig V, Gosert R, Walti CS, Prince SS, Halter J, Mathews R, Stühler C, Khanna N, and Leuzinger K
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In allogeneic hematopoietic cell transplant (HCT)-recipients, prophylactic management strategies are essential for preventing CMV-reactivation and associated disease. We report on a 63-year-old male patient with a D-/R+ CMV-serostatus, who showed ongoing low-level CMV-replication post-HCT despite receiving letermovir prophylaxis. Sanger-sequencing failed to detect drug resistance mutations (DRM) until CMV-pneumonitis developed, revealing a UL56-C325R-DRM linked to high-level letermovir resistance. Retrospective analysis with next-generation-sequencing (NGS) revealed the DRM at a low frequency of 6% two weeks prior to detection by Sanger-sequencing. This study highlights the importance of advanced NGS-methods for early detection of CMV-DRMs, allowing for faster adjustments in antiviral treatment strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2024
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9. Minimal residual disease monitoring by Ig/TCR gene rearrangements predicts post-transplant relapse and survival in adult patients with acute lymphoblastic leukemia.
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Bader MS, Kubetzko S, Schäfer BW, Arranto C, Drexler B, Halter J, Passweg JR, and Medinger M
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- 2024
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10. Influence of comorbidities on outcome in 1102 patients with an allogeneic hematopoietic stem cell transplantation.
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Janscak M, Stelmes A, van den Berg J, Heim D, Halter J, Drexler B, Arranto C, Passweg J, and Medinger M
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The hematopoietic comorbidity risk index (HCT-CI) is a pre-transplant risk assessment tool used to qualify comorbidities to predict non-relapse mortality (NRM) of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). HSCT procedures continue to improve. Therefore, the predictive value of HCT-CI needs to be re-evaluated. Our study is a retrospective analysis of pre-existing comorbidities assessing the relevance of the HCT-CI on the outcome of consecutive patients (n = 1102) undergoing allo-HSCT from 2006-2021. HCT-CI was classified as low (HCT-CI 0), intermediate (HCT-CI 1-2) and high-risk (HCT-CI ≥ 3). At 10 years, NRM for low, intermediate, and high-risk HCT-CI group was 21.0%, 26.0%, and 25.8% (p = 0.04). NRM difference was significant between low to intermediate (p < 0.001), but not between intermediate to high-risk HCT-CI (p = 0.22). Overall survival (OS) at 10 years differed significantly with 49.9%, 39.8%, and 31.1%, respectively (p < 0.001). In multivariate analysis of HCT-CI organ subgroups, cardiac disease was most strongly associated with NRM (HR = 1.73, p = 0.02) and OS (HR = 1.77, p < 0.001). All other individual organ comorbidities influenced NRM to a lesser extent. Further, donor (HR = 2.20, p < 0.001 for unrelated and HR = 2.17, p = 0.004 for mismatched related donor), disease status (HR = 1.41, p = 0.03 for advanced disease) and previous HSCT (HR = 1.55, p = 0.009) were associated with NRM. Improvement in transplant techniques and supportive care may have improved outcome with respect to comorbidities., (© 2024. The Author(s).)
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- 2024
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11. Allogeneic haematopoietic cell transplantation for chronic myeloid leukaemia in Switzerland in the face of rapid development of effective drugs.
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Heim D, Baldomero H, Medinger M, Masouridi-Levrat S, Schanz U, Nair G, Güngör T, Halter J, Passweg JR, and Chalandon Y
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- Humans, Switzerland, Male, Female, Adult, Middle Aged, Adolescent, Transplantation Conditioning methods, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myelogenous, Chronic, BCR-ABL Positive therapy, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Transplantation, Homologous methods, Protein Kinase Inhibitors therapeutic use
- Abstract
Aim: Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was the main indication for allogeneic HCT. The introduction of tyrosine kinase inhibitors changed the treatment of CML patients dramatically. Allogeneic HCT was rapidly replaced by tyrosine kinase inhibitors as first-line treatment for CML, and the indication shifted to the treatment of non-responders, patients intolerant to tyrosine kinase inhibitors and patients whose CML is transforming to the accelerated phase and blast crisis. This paper describes changes in the use of transplantation technology for CML patients in the face of rapid drug development., Methods: All patients receiving a transplant for CML between 1997 and 2021 in Switzerland were included in the study. For the purpose of this analysis, time periods were analysed in quinquennia, 1997-2001 (Q1), 2002-2006 (Q2), 2007-2011 (Q3), 2012-2016 (Q4) and 2017-2021 (Q5), as the observation period spanned 25 years., Results: Overall, 239 patients received a transplant. These included 96 in Q1, 56 in Q2, 25 in Q3, 34 in Q4 and 28 in Q5. Patient characteristics changed over time: recent patients were older and had a longer interval from diagnosis to transplantation because of tyrosine kinase inhibitor treatment. However, the proportions of patients receiving transplants during an early versus advanced disease stage differed little. Transplant technology changed, as well. Patients received intensive conditioning regimens less often due to higher age and more commonly had peripheral blood as opposed to bone marrow transplants. However, the type of stem cell donor selected did not differ. In a univariable analysis, there were no significant differences in survival, progression-free survival, non-relapse mortality, relapse incidence or incidences of acute and chronic graft-versus-host disease among the five quinquennia. In a multivariable analysis, older age, donors other than HLA-identical siblings and more advanced disease stage, but not the quinquennium, were associated with higher risk of death., Conclusion: Since the introduction of tyrosine kinase inhibitors haematopoietic cell transplantation has been used less frequently to treat CML. Patients in recent cohorts received transplants at an older age and later in the disease course; despite these higher risks, the outcome of allogeneic HCT has not worsened over time but has not improved, either. As the outcome is worse in advanced phases, it is important to conduct transplants before disease progression. Therefore, patients with advanced disease should be monitored closely and receive transplants in time.
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- 2024
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12. True Donor Cell Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Considerations-Brief Report.
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Hoffmann M, Banz Y, Halter J, Schoumans J, Tchinda J, Bacher U, and Pabst T
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- Humans, Adult, Female, Leukemia therapy, Tissue Donors, Male, Hematopoietic Stem Cell Transplantation adverse effects, Transplantation, Homologous
- Abstract
Donor cell leukemia (DCL) is a rare complication after allogeneic hematopoietic stem cell transplantation (HSCT) accounting for 0.1% of relapses and presenting as secondary leukemia of donor origin. Distinct in phenotype and cytogenetics from the original leukemia, DCL's clinical challenge lies in its late onset. Its origin is affected by donor cell anomalies, transplant environment, and additional mutations. A 43-year-old woman, treated for early stage triple-negative breast cancer, developed mixed-phenotype acute leukemia (MPAL), 12 years later. Following induction chemotherapy, myeloablative conditioning, and allo-HSCT from her fully HLA-matched brother, she exhibited multiple cutaneous relapses of the original leukemia, subsequently evolving into DCL of the bone marrow. Cytogenetic analysis revealed a complex male karyotype in 20 out of 21 metaphases, however, still showing the MPAL phenotype. DCL diagnosis was confirmed by 90.5% XY in FISH analysis and the male karyotype. Declining further intensive chemotherapy including a second allo-HSCT, she was subsequently treated with repeated radiotherapy, palliative systemic therapies, and finally venetoclax and navitoclax but died seven months post-DCL diagnosis. This case underlines DCL's complexity, characterized by unique genetics, further complicating diagnosis. It highlights the need for advanced diagnostic techniques for DCL identification and underscores the urgency for early detection and better prevention and treatment strategies.
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- 2024
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13. Pharmacokinetic Modeling and Simulation with Pharmacogenetic Insights Support the Relevance of Therapeutic Drug Monitoring for Myeloablative Busulfan Dosing in Adult HSCT.
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Ben Hassine K, Seydoux C, Khier S, Daali Y, Medinger M, Halter J, Heim D, Chalandon Y, Schanz U, Nair G, Cantoni N, Passweg JR, Satyanarayana Uppugunduri CR, and Ansari M
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- Adult, Humans, Child, Pharmacogenetics, Drug Monitoring, Obesity, Busulfan therapeutic use, Hematopoietic Stem Cell Transplantation
- Abstract
Therapeutic drug monitoring (TDM) of busulfan (Bu) is well-established in pediatric hematopoietic stem cell transplantation (HSCT), but its use in adults is limited due to a lack of clear recommendations and scarcity of evidence regarding its utility. GSTA1 promoter variants are reported to affect Bu clearance in both adults and pediatric patients. This study aimed to evaluate the value of preemptive genotyping GSTA1 and body composition (obesity) in individualizing Bu dosing in adults, through pharmacokinetic (PK) modeling and simulations. A population pharmacokinetic (PopPK) model was developed and validated with data from 60 adults who underwent HSCT. Simulations assessed different dosing scenarios based on body size metrics and GSTA1 genotypes. Due to the limited number of obese patients in the cohort, the effect of obesity on Bu pharmacokinetics (PK) was evaluated in silico using a physiologically-based pharmacokinetic (PBPK) model and relevant virtual populations from Simcyp software. Patients with at least 1 GSTA1*B haplotype had 17% lower clearance on average. PopPK simulations indicated that adjusting doses based on genotype increased the probability of achieving the target exposure (3.7 to 5.5 mg.h/L) from 53% to 60 % in GSTA1*A homozygous patients, and from 50% to 61% in *B carriers. Still, Approximately 40% of patients would not achieve this therapeutic window without TDM. A 2-sample optimal design was validated for routine model-based Bu first dose AUC
0-∞ estimation, and the model was implemented in the Tucuxi user-friendly TDM software. PBPK simulations confirmed body surface area-based doses of 29 to 31 mg/m2 /6h as the most appropriate, regardless of obesity status. This study emphasizes the importance of individualized Bu dosing strategies in adults to achieve therapeutic targets. Preemptive genotyping alone may not have a significant clinical impact, and routine TDM may be necessary for optimal transplantation outcomes., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
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14. Oral Candida carriage and resistance against common antifungal agents in hematopoietic stem cell transplantation recipients.
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Mauramo M, Tonoz N, Halter J, Joseph B, and Waltimo T
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- Humans, Candida, Fluconazole pharmacology, Prospective Studies, Microbial Sensitivity Tests, Candida glabrata, Antifungal Agents pharmacology, Antifungal Agents therapeutic use, Hematopoietic Stem Cell Transplantation
- Abstract
Purpose: Allogeneic hematopoietic stem cell transplant (HSCT) recipients receiving long-term and high-dose immunosuppressive medications suffer commonly from oral candida infections. This prospective cohort study examined oral fungal carriage in HSCT recipients and screened the susceptibility against commonly used antifungal agents. An increasing oral occurrence of Candida spp. and the development of resistance against clinically administered fluconazole were hypothesized., Methods: Two hundred HSCT recipients were included and followed up for 2 years post-HSCT. Oral microbiological specimens were analyzed with matrix-assisted laser desorption/ionization-time of flight mass spectrometry assays (MALDI-TOF). The colorimetric method was applied for the susceptibility testing by commercially available Sensititre YeastOne (SYO®, TREK Diagnostics Systems, Thermo-Fisher, UK)., Results: The prevalence of oral Candida spp. carriage increased statistically significantly after a year post-HSCT being 30, 26, 35, 44, and 47%, pre-HSCT, 3, 6, 12, and 24 months post-HSCT, respectively. Altogether, 169 clinical oral Candida strains were isolated. Fourteen Candida spp. were identified, and C. albicans was predominant in 74% of the isolates pre-HSCT with a descending prevalence down to 44% 2 years post-HSCT. An increasing relative proportion of non-albicans species post-HSCT was evident. No development of resistance of C. albicans against fluconazole was found. Instead, a shift from C. albicans towards non-albicans species, especially C. dubliensis, C. glabrata, and relatively seldom found C. krusei, was observed., Conclusion: Oral Candida carriage increases after HSCT. Instead of the expected development of resistance of C. albicans against fluconazole, the relative proportion of non-albicans strains with innate resistance against azole-group antifungals increased., (© 2024. The Author(s).)
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- 2024
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15. Post-transplant Inflammatory Bowel Disease Associated with Donor-Derived TIM-3 Deficiency.
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Baldrich A, Althaus D, Menter T, Hirsiger JR, Köppen J, Hupfer R, Juskevicius D, Konantz M, Bosch A, Drexler B, Gerull S, Ghosh A, Meyer BJ, Jauch A, Pini K, Poletti F, Berkemeier CM, Heijnen I, Panne I, Cavelti-Weder C, Niess JH, Dixon K, Daikeler T, Hartmann K, Hess C, Halter J, Passweg J, Navarini AA, Yamamoto H, Berger CT, Recher M, and Hruz P
- Subjects
- Humans, Cytokines metabolism, Intestinal Mucosa, Hepatitis A Virus Cellular Receptor 2 genetics, Inflammatory Bowel Diseases diagnosis, Inflammatory Bowel Diseases etiology, Stem Cell Transplantation adverse effects
- Abstract
Inflammatory bowel disease (IBD) occurring following allogeneic stem cell transplantation (aSCT) is a very rare condition. The underlying pathogenesis needs to be better defined. There is currently no systematic effort to exclude loss- or gain-of-function mutations in immune-related genes in stem cell donors. This is despite the fact that more than 100 inborn errors of immunity may cause or contribute to IBD. We have molecularly characterized a patient who developed fulminant inflammatory bowel disease following aSCT with stable 100% donor-derived hematopoiesis. A pathogenic c.A291G; p.I97M HAVCR2 mutation encoding the immune checkpoint protein TIM-3 was identified in the patient's blood-derived DNA, while being absent in DNA derived from the skin. TIM-3 expression was much decreased in the patient's serum, and in vitro-activated patient-derived T cells expressed reduced TIM-3 levels. In contrast, T cell-intrinsic CD25 expression and production of inflammatory cytokines were preserved. TIM-3 expression was barely detectable in the immune cells of the patient's intestinal mucosa, while being detected unambiguously in the inflamed and non-inflamed colon from unrelated individuals. In conclusion, we report the first case of acquired, "transplanted" insufficiency of the regulatory TIM-3 checkpoint linked to post-aSCT IBD., (© 2024. The Author(s).)
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- 2024
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16. Correction: Effect of pharmacokinetics and pharmacogenomics in adults with allogeneic hematopoietic cell transplantation conditioned with Busulfan.
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Seydoux C, Uppugunduri CRS, Medinger M, Nava T, Halter J, Heim D, Chalandon Y, Schanz U, Nair G, Cantoni N, Passweg JR, and Ansari M
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- 2024
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17. Effect of pharmacokinetics and pharmacogenomics in adults with allogeneic hematopoietic cell transplantation conditioned with Busulfan.
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Seydoux C, Uppugunduri CRS, Medinger M, Nava T, Halter J, Heim D, Chalandon Y, Schanz U, Nair G, Cantoni N, Passweg JR, and Ansari M
- Subjects
- Adult, Humans, Busulfan therapeutic use, Busulfan pharmacokinetics, Pharmacogenetics, Cyclophosphamide therapeutic use, Polymorphism, Genetic, Transplantation Conditioning, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease drug therapy
- Abstract
Busulfan (Bu) combined with cyclophosphamide (Cy) is commonly used as a myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). There is inter-individual variability of Bu pharmacokinetics (PK) and hence in toxicity and efficacy. The introduction of therapeutic drug monitoring (TDM) of Bu has decreased toxicity of the regimen. Hepatic metabolism of Bu is mediated through Glutathione-S-Transferases (GSTs), mainly GSTA1. Patients with GSTA1*A variants are considered normal metabolizers and GSTA1*B corresponds to poor metabolism, defined by nucleotide changes at -52 or -69 locus in GSTA1 promoter region. The aim of the study was to explore the correlation between GSTA1 polymorphisms and Bu-PK in 60 adult patients receiving an allo-HCT in the BuCyBu clinical study (ClinicalTrials.gov I, ID NCT01779882) comparing the sequence BuCy to CyBu. DNA samples prior to conditioning were genotyped for candidate variants at -52 (rs3957356) and -69 (rs3957357) loci in the GSTA1 promoter. Thirty-three % of patients were GSTA1*A*A, 49% GSTA1*A*B and 18% GSTA1*B*B. In GSTA1*A*A patients, median Bu-AUC was 3.6 ± 0.7 mg*h/L, in GSTA1*A*B 4.5 ± 1.6 and in GSTA1*B*B 4.9 ± 1.4 (AUC 35% higher than GSTA1*A*A, p = 0.03), with a similar significant correlation with Bu-clearance (p = 0.04). The correlation between GSTA1 polymorphism and AUC remained significant in multivariate linear regression analysis. There was a trend for lower non-relapse mortality (NRM) in patients with low AUC. We could not demonstrate a correlation between GSTA1 polymorphisms and NRM, acute graft-versus-host disease (aGvHD) in this small cohort, but there is a trend of higher aGvHD incidence in GSTA1*B*B patients., (© 2023. The Author(s).)
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- 2023
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18. BleedHD-a new electronic assessment tool for grading chronic graft-versus-host disease validated in a multicenter and multiprofessional setting.
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Warthmann A, Holbro A, Buser A, Schefer S, Degen Kellerhals S, Ravelli M, Passweg J, Stussi G, and Halter J
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- Humans, Chronic Disease, Bronchiolitis Obliterans Syndrome, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease diagnosis
- Published
- 2023
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19. Dynamics of antibody titers to SARS-CoV-2 and clinical outcomes after sotrovimab pre-exposure prophylaxis early after allogeneic hematopoietic stem cell transplantation.
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Capoferri G, Walti CS, Urwyler P, Ragozzino S, Passweg JR, Halter J, Battegay M, Baettig V, Weisser M, Arnold B, Morin B, Guetlin Y, Torres DA, Barut GT, Thiel V, Egli A, Drexler B, and Khanna N
- Subjects
- Humans, SARS-CoV-2, Pre-Exposure Prophylaxis, COVID-19, Hematopoietic Stem Cell Transplantation
- Published
- 2023
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20. Safety and Feasibility of Immunoadsorption with Heparin Anticoagulation in Preparation of ABO-Incompatible Kidney Transplantation: A Retrospective Single-Center Study.
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Junker T, Volken T, Stehle G, Drexler B, Infanti L, Buser A, Passweg J, Schaub S, Dickenmann M, Halter J, and Holbro A
- Abstract
Introduction: Immunoadsorption (IA) of isohemagglutinins is an often-crucial procedure in preparation of major ABO blood group-incompatible living donor kidney transplantation (ABOi LDKT). Standard citrate-based anticoagulation during the procedure has potential disadvantages for distinct patient groups. In this study, we report our experience with an alternative anticoagulation scheme using heparin during IA for selected patients., Methods: We conducted a retrospective analysis of all patients who underwent IA with heparin anticoagulation between February 2013 and December 2019 at our institution with focus on the safety and efficacy of the adapted procedure. For further validation, we compared graft function, graft survival, and overall survival with those of all recipients of living donor kidney transplants with or without pretransplant desensitizing apheresis for ABO antibodies at our institution during the same period., Results: In thirteen consecutive patients prepared for ABOi LDKT with IA with heparin anticoagulation, no major bleeding or other significant complications were observed. All patients achieved sufficient isohemagglutinin titer reduction to proceed to transplant surgery. Graft function, graft survival, and overall survival did not significantly differ from patients treated with standard anticoagulation for IA or ABO compatible recipients of living donor kidneys., Conclusion: IA with heparin in preparation of ABOi LDKT is safe and feasible for selected patients after internal validation., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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21. Chronic gvhd dictionary-eurograft cost action initiative consensus report.
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Zelić Kerep A, Olivieri A, Schoemans H, Lawitschka A, Halter J, Pulanic D, Dickinson A, Greinix HT, Pavletic SZ, Schultz KR, Lee SJ, and Wolff D
- Subjects
- Adolescent, Humans, Child, Chronic Disease, Consensus, Quality of Life, Graft vs Host Disease etiology, Graft vs Host Disease diagnosis, Hematopoietic Stem Cell Transplantation, Bronchiolitis Obliterans Syndrome
- Abstract
Chronic graft versus host disease (cGVHD) affects patients after allogeneic hematopoietic stem cell transplantation (alloHSCT). This orphan disease poses a challenge for clinicians and researchers. The purpose of the cGVHD Dictionary is to provide a standardized structure for cGVHD databases on an international level, reconciling differences in data retrieval and facilitate database merging. It is derived from several consensus meetings of the EUROGRAFT consortium (European Cooperation in Science and Technology-COST Action CA17138) followed by a consensus process involving European Society for Blood and Marrow Transplantation (EBMT), US GvHD consortium and Center for International Bone Marrow Transplant Registry (CIBMTR). Databases used for the dictionary were: the National Institutes of Health (NIH) database, the Center for International Blood and Marrow Transplant Research, Applying Biomarkers to Minimize Long Term Effects of Childhood/Adolescent Cancer Treatment - Pediatric Blood and Marrow Transplant Consortium database, EBMT registry, the German-Austrian-Swiss GvHD registry, Italian Blood and Marrow Transplantation Society registry and Regensburg-Göttingen-Newcastle HSCT dataset. A four-part cGVHD Dictionary was formed based on the databases, consensus, and evidence in the literature. The Dictionary is divided into: (1) Patient characteristics, (2) Transplant characteristics, (3) cGVHD characteristics and (4) patient-reported quality of life, symptom burden and functional indicators., (© 2022. The Author(s).)
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- 2023
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22. Feasibility of electronic patient-reported outcome monitoring and self-management program in aplastic anemia and paroxysmal nocturnal hemoglobinuria-a pilot study (ePRO-AA-PNH).
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Bänziger S, Weisshaar K, Arokoski R, Gerull S, Halter J, Rovó A, Bargetzi M, Goede JS, Senft Y, Valenta S, Passweg JR, and Drexler B
- Subjects
- Humans, Pilot Projects, Feasibility Studies, Patient Reported Outcome Measures, Electronics, Anemia, Aplastic therapy, Hemoglobinuria, Paroxysmal therapy, Hemoglobinuria, Paroxysmal diagnosis, Self-Management
- Abstract
Introduction: Electronic patient-reported outcomes (ePRO) are increasingly recognized in health care, as they have been demonstrated to improve patient outcomes in cancer, but have been less studied in rare hematological diseases. The aim of this study was to develop and test the feasibility of an ePRO system specifically customized for aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH)., Methods: After performing a user-centered design evaluation an ePRO system for AA and PNH patients could be customized and the application was tested by patients and their medical teams for 6 months. Symptom-reporting triggered self-management advice for patients and prompts them to contact clinicians in case of severe symptoms, while the medical team received alerts of severe symptoms for patient care., Results: All nine included patients showed a high adherence rate to the weekly symptom-reporting (72%) and reported high satisfaction. The system was rated high for usage, comprehensibility, and integration into daily life. Most patients (78%) would continue and all would recommend the application to other AA/PNH patients. Technical performance was rarely a barrier and healthcare providers saw ePRO-AA-PNH as a useful supplement, but the lacking integration into the hospital information system was identified as a major barrier to usage., Conclusion: An ePRO system customized for AA and PNH was feasible in terms of adherence, satisfaction, and performance, showing a high potential for these rare conditions in terms of data collection and patient guidance. However, the integration into clinical workflows is crucial for further routine use., Trial Registration: ClinicalTrials.gov NCT04128943., (© 2022. The Author(s).)
- Published
- 2023
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23. Impact of busulfan pharmacokinetics on outcome in adult patients receiving an allogeneic hematopoietic cell transplantation.
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Seydoux C, Battegay R, Halter J, Heim D, Rentsch KM, Passweg JR, and Medinger M
- Subjects
- Adult, Area Under Curve, Busulfan, Humans, Recurrence, Transplantation Conditioning adverse effects, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Busulfan (Bu) is widely used in conditioning regimens before allogeneic hematopoietic cell transplantation, with variable metabolism due to interindividual differences of pharmacokinetics (PK). The purpose of this study was to correlate pharmacokinetics and clinical outcomes. Lower-AUC, in range-AUC and higher-AUC were defined as ±25% of the targeted Bu-AUC. In 2019, we changed Bu dosing from 4×/day (Bu-4) to 1×/day (Bu-1) for ease of application. AUC-target range was reached in 46% of patients; 40% were in low-AUC and 14% in high-AUC. Among all toxicities, viral and fungal infections were significantly more frequent in high-AUC compared with low-AUC (20% vs. 8%; p = 0.01 and 37% vs. 17%; p = 0.03). Bu-1 showed lower PK values (66% vs. 36% of Bu-4 in low-AUC; p < 0.01) and higher incidence of mucositis (p = 0.02). Long-term outcomes at 2 years showed a higher non-relapse mortality (NRM) (p < 0.01) and higher relative risk of death in the high-AUC group compared to the other groups. Cumulative incidence of relapse and acute/chronic GvHD were not significantly different. The optimal cut-off in Bu-AUC associated with low NRM was 969 µmol/l*min (ROC AUC 0.67, sensitivity 0.86 and specificity 0.47) for Bu-4. In conclusion, low-AUC BU-PK seems of benefit regarding NRM and survival., (© 2022. The Author(s).)
- Published
- 2022
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24. Antibody response to mRNA SARS-CoV-2 vaccination in 182 patients after allogeneic hematopoietic cell transplantation.
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Beerlage A, Leuzinger K, Valore L, Mathew R, Junker T, Drexler B, Passweg JR, Hirsch HH, and Halter J
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- Antibodies, Viral, Antibody Formation, COVID-19 Vaccines, Humans, RNA, Messenger, SARS-CoV-2, Vaccination, COVID-19 prevention & control, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Introduction: Patients after allogeneic stem cell transplantation are at high risk for infection-related complications, and vaccination efficacy might be impaired depending on the immune reconstitution. In this study, we evaluate their response to mRNA vaccines against SARS-CoV-2., Methods: During routine follow-up visits, patients were asked about their vaccination status and if they had a previous infection with SARS-CoV-2. In fully vaccinated patients, the antibody titer was measured using the Roche Elecsys Anti-SARS-CoV-2 S test. A titer of <1 U/L was considered as negative, titers of ≥250 U/ml as a high antibody titer, and a titer of 50-249 U/ml as a low antibody titer. Patient characteristics were evaluated by chart review to identify risk factors for poor vaccination response., Results: The majority of patients developed a high antibody titer (138 out 182 patients, 75.8%). Risk factors for a low antibody titer were immunosuppressive therapy, a lymphocyte count <0.9 G/L, ongoing treatment for the underlying malignancy, and active graft-versus-host disease (GvHD). Donor type, underlying disease, a previous SARS-CoV-2 infection, and sex did not significantly influence the response to the vaccination., Discussion: While patients undergoing allogeneic stem cell transplantation have been excluded from the initial registration trials, our real-world experience with a large patient cohort confirms the data of previous studies, showing that most patients do have a good response to mRNA vaccines against SARS-CoV-2. Nevertheless, a significant proportion of patients shows an inadequate vaccination, which can be improved after a third vaccination in most cases despite immunosuppressive therapy., (© 2022 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)
- Published
- 2022
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25. Scarce data on skin microbiome in graft-versus-host disease after allogenic haematopoietic cell transplantation - a systematic review.
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Schumacher M, Egli A, Mari A, Navarini AA, Halter JP, and Müller SM
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- Humans, Skin, Transplantation, Homologous adverse effects, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation adverse effects, Microbiota
- Published
- 2022
- Full Text
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26. Association of Host Factors With Antibody Response to Seasonal Influenza Vaccination in Allogeneic Hematopoietic Stem Cell Transplant Patients.
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Linnik J, Syedbasha M, Kaltenbach HM, Vogt D, Hollenstein Y, Kaufmann L, Cantoni N, Ruosch-Girsberger S, Müller AMS, Schanz U, Pabst T, Stüssi G, Weisser M, Halter J, Stelling J, and Egli A
- Subjects
- Antibodies, Viral, Antibody Formation, Cohort Studies, Humans, Influenza A Virus, H3N2 Subtype, Seasons, Vaccination, Hematopoietic Stem Cell Transplantation, Influenza A Virus, H1N1 Subtype, Influenza Vaccines adverse effects, Influenza, Human prevention & control
- Abstract
Background: Influenza vaccination efficacy is reduced after hematopoietic stem cell transplantation (HSCT) and patient factors determining vaccination outcomes are still poorly understood., Methods: We investigated the antibody response to seasonal influenza vaccination in 135 HSCT patients and 69 healthy volunteers (HVs) in a prospective observational multicenter cohort study. We identified patient factors associated with hemagglutination inhibition titers against A/California/2009/H1N1, A/Texas/2012/H3N2, and B/Massachusetts/2012 by multivariable regression on the observed titer levels and on seroconversion/seroprotection categories for comparison., Results: Both regression approaches yielded consistent results but regression on titers estimated associations with higher precision. HSCT patients required 2 vaccine doses to achieve average responses comparable to a single dose in HVs. Prevaccination titers were positively associated with time after transplantation, confirming that HSCT patients can elicit potent antibody responses. However, an unrelated donor, absolute lymphocyte counts below the normal range, and treatment with calcineurin inhibitors lowered the odds of responding., Conclusions: HSCT patients show a highly heterogeneous vaccine response but, overall, patients benefited from the booster shot and can acquire seroprotective antibodies over the years after transplantation. Several common patient factors lower the odds of responding, urging identification of additional preventive strategies in the poorly responding groups., Clinical Trials Registration: NCT03467074., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2022
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27. Outcomes of Allogeneic Hematopoietic Cell Transplantation in T Cell Prolymphocytic Leukemia: A Contemporary Analysis from the Center for International Blood and Marrow Transplant Research.
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Murthy HS, Ahn KW, Estrada-Merly N, Alkhateeb HB, Bal S, Kharfan-Dabaja MA, Dholaria B, Foss F, Gowda L, Jagadeesh D, Sauter C, Abid MB, Aljurf M, Awan FT, Bacher U, Badawy SM, Battiwalla M, Bredeson C, Cerny J, Chhabra S, Deol A, Diaz MA, Farhadfar N, Freytes C, Gajewski J, Gandhi MJ, Ganguly S, Grunwald MR, Halter J, Hashmi S, Hildebrandt GC, Inamoto Y, Jimenez-Jimenez AM, Kalaycio M, Kamble R, Krem MM, Lazarus HM, Lazaryan A, Maakaron J, Munshi PN, Munker R, Nazha A, Nishihori T, Oluwole OO, Ortí G, Pan DC, Patel SS, Pawarode A, Rizzieri D, Saba NS, Savani B, Seo S, Ustun C, van der Poel M, Verdonck LF, Wagner JL, Wirk B, Oran B, Nakamura R, Scott B, and Saber W
- Subjects
- Humans, Middle Aged, Transplantation Conditioning adverse effects, Transplantation, Homologous adverse effects, Graft vs Host Disease epidemiology, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Prolymphocytic, T-Cell therapy
- Abstract
T cell prolymphocytic leukemia (T-PLL) is a rare, aggressive malignancy with limited treatment options and poor long-term survival. Previous studies of allogeneic hematopoietic cell transplantation (alloHCT) for T-PLL are limited by small numbers, and descriptions of patient and transplantation characteristics and outcomes after alloHCT are sparse. In this study, we evaluated outcomes of alloHCT in patients with T-PLL and attempted to identify predictors of post-transplantation relapse and survival. We conducted an analysis of data using the Center for International Blood and Marrow Transplant Research database on 266 patients with T-PLL who underwent alloHCT between 2008 and 2018. The 4-year rates of overall survival (OS), disease-free survival (DFS), relapse, and treatment-related mortality (TRM) were 30.0% (95% confidence interval [CI], 23.8% to 36.5%), 25.7% (95% CI, 20% to 32%), 41.9% (95% CI, 35.5% to 48.4%), and 32.4% (95% CI, 26.4% to 38.6%), respectively. In multivariable analyses, 3 variables were associated with inferior OS: receipt of a myeloablative conditioning (MAC) regimen (hazard ratio [HR], 2.18; P < .0001), age >60 years (HR, 1.61; P = .0053), and suboptimal performance status, defined by Karnofsky Performance Status (KPS) <90 (HR, 1.53; P = .0073). Receipt of an MAC regimen also was associated with increased TRM (HR, 3.31; P < .0001), an elevated cumulative incidence of grade II-IV acute graft-versus-host disease (HR, 2.94; P = .0011), and inferior DFS (HR, 1.86; P = .0004). Conditioning intensity was not associated with relapse; however, stable disease/progression was correlated with increased risk of relapse (HR, 2.13; P = .0072). Both in vivo T cell depletion (TCD) as part of conditioning and KPS <90 were associated with worse TRM and inferior DFS. Receipt of total body irradiation had no significant effect on OS, DFS, or TRM. Our data show that reduced-intensity conditioning without in vivo TCD (ie, without antithymocyte globulin or alemtuzumab) before alloHCT was associated with long-term DFS in patients with T-PLL who were age ≤60 years or who had a KPS >90 or chemosensitive disease., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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28. Feasibility and efficacy of salvage allogeneic stem cell transplantation in AML patients relapsing after autologous stem cell transplantation.
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Shumilov E, Shakhanova I, Flach J, Schmidt N, Buerki S, Legros M, Kronig MN, Ofran Y, Gerull S, Medinger M, Taleghani BM, Passweg J, Halter J, Bacher U, and Pabst T
- Subjects
- Feasibility Studies, Humans, Neoplasm Recurrence, Local, Remission Induction, Retrospective Studies, Salvage Therapy, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
- Abstract
Autologous hematopoietic cell transplantation (HCT) is suitable for consolidation of favorable-/intermediate-risk AML patients in CR1. However, ~50% of AML patients relapse after autologous HCT, and efficacy of subsequent salvage strategies including allogeneic HCT remains unclear. We studied 123 consecutive patients with newly diagnosed AML undergoing high-dose chemotherapy (HDCT)/autologous HCT in CR1. In relapsing patients afterwards, we analyzed salvage treatments and outcomes focusing particularly on salvage allogeneic HCT. Of 123 patients, 64 (52%) relapsed after autologous HCT. Subsequently, 13 (21%) received palliative therapy, whereas 51 (79%) proceeded to salvage therapy with a curative intent. Of the 47 patients with a curative intent and who did not proceed directly to allogeneic HCT, 23 (49%) achieved CR2 or had ongoing hematologic CR1 despite molecular relapse. Finally, 30 patients (47%) received allogeneic HCT with estimated 3-year leukemia-free and overall survival rates of 33% and 43%. Hematologic remission at allogeneic HCT and lack of acute GvHD had a positive impact on OS and LFS (p < 0.05). Our study suggests that almost 80% of AML patients can undergo salvage therapy following relapse after front-line HDCT/autologous HCT. Allogeneic HCT can provide cure in one third of patients relapsing after front-line HDCT/autologous HCT., (© 2021. The Author(s).)
- Published
- 2022
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- View/download PDF
29. Model-based inference of neutralizing antibody avidities against influenza virus.
- Author
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Linnik J, Syedbasha M, Hollenstein Y, Halter J, Egli A, and Stelling J
- Subjects
- Hemagglutination Inhibition Tests, Hemagglutinin Glycoproteins, Influenza Virus, Humans, Influenza A Virus, H1N1 Subtype, Neutralization Tests, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, Antibody Affinity immunology, Immunogenicity, Vaccine immunology, Influenza, Human immunology, Models, Immunological
- Abstract
To assess the response to vaccination, quantity (concentration) and quality (avidity) of neutralizing antibodies are the most important parameters. Specifically, an increase in avidity indicates germinal center formation, which is required for establishing long-term protection. For influenza, the classical hemagglutination inhibition (HI) assay, however, quantifies a combination of both, and to separately determine avidity requires high experimental effort. We developed from first principles a biophysical model of hemagglutination inhibition to infer IgG antibody avidities from measured HI titers and IgG concentrations. The model accurately describes the relationship between neutralizing antibody concentration/avidity and HI titer, and explains quantitative aspects of the HI assay, such as robustness to pipetting errors and detection limit. We applied our model to infer avidities against the pandemic 2009 H1N1 influenza virus in vaccinated patients (n = 45) after hematopoietic stem cell transplantation (HSCT) and validated our results with independent avidity measurements using an enzyme-linked immunosorbent assay with urea elution. Avidities inferred by the model correlated with experimentally determined avidities (ρ = 0.54, 95% CI = [0.31, 0.70], P < 10-4). The model predicted that increases in IgG concentration mainly contribute to the observed HI titer increases in HSCT patients and that immunosuppressive treatment is associated with lower baseline avidities. Since our approach requires only easy-to-establish measurements as input, we anticipate that it will help to disentangle causes for poor vaccination outcomes also in larger patient populations. This study demonstrates that biophysical modelling can provide quantitative insights into agglutination assays and complement experimental measurements to refine antibody response analyses., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2022
- Full Text
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30. Short- and long-term impact of neutropenia within the first year after kidney transplantation.
- Author
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Ingold L, Halter J, Martinez M, Amico P, Wehmeier C, Hirt-Minkowski P, Steiger J, Dickenmann M, and Schaub S
- Subjects
- Graft Rejection etiology, Humans, Mycophenolic Acid, Retrospective Studies, Kidney Transplantation adverse effects, Neutropenia etiology
- Abstract
The aim of this retrospective single-center study was to investigate the short- and long-term impact of neutropenia occurring within the first year after kidney transplantation, with a special emphasis on different neutropenia grades. In this unselected cohort, 225/721 patients (31%) developed 357 neutropenic episodes within the first year post-transplant. Based on the nadir neutrophil count, patients were grouped as neutropenia grade 2 (<1.5-1.0*10
9 /l; n = 105), grade 3 (<1.0-0.5*109 /l; n = 65), and grade 4 (<0.5*109 /l; n = 55). Most neutropenia episodes were presumably drug-related (71%) and managed by reduction/discontinuation of potentially responsible drugs (mycophenolic acid [MPA] 51%, valganciclovir 25%, trimethoprim/sulfamethoxazole 19%). Steroids were added/increased as replacement for reduced/discontinued MPA. Granulocyte colony-stimulating factor was only used in 2/357 neutropenia episodes (0.6%). One-year incidence of (sub)clinical rejection, one-year mortality, and long-term patient and graft survival were not different among patients without neutropenia and neutropenia grade 2/3/4. However, the incidence of infections was about 3-times higher during neutropenia grade 3 and 4, but not increased during grade 2. In conclusion, neutropenia within the first year after kidney transplantation represents no increased risk for rejection and has no negative impact on long-term patient and graft survival. Adding/increasing steroids as replacement for reduced/discontinued MPA might supplement management of neutropenia., (© 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)- Published
- 2021
- Full Text
- View/download PDF
31. Analysis of biological models to predict clinical outcomes based on HLA-DPB1 disparities in unrelated transplantation.
- Author
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Buhler S, Baldomero H, Ferrari-Lacraz S, Mamez AC, Masouridi-Levrat S, Heim D, Halter J, Nair G, Chalandon Y, Schanz U, Güngör T, Nicoloso G, Passweg JR, and Villard J
- Subjects
- HLA-DP beta-Chains, Histocompatibility Testing, Humans, Models, Biological, Prospective Studies, Epitopes, T-Lymphocyte, Unrelated Donors
- Abstract
HLA compatibility is a key factor for survival after unrelated hematopoietic stem cell transplantation (HSCT). HLA-A, -B, -C, -DRB1, and -DQB1 are usually matched between donor and recipient. By contrast, HLA-DPB1 mismatches are frequent, although it is feasible to optimize donor selection and DPB1 matching with prospective typing. Because classical DPB1 allele mismatches are often unavoidable, however, several biological models have been developed to predict the optimal DPB1 mismatch combination for less graft-versus-host disease (GVHD) and better overall survival. In 909 recipient/donor pairs, we analyzed the role of 3 biological models: T-cell epitopes (TCEs) based on the immunogenicity of DPB1, cell surface expression of DPB1 molecules based on a single-nucleotide polymorphism located in the 3' untranslated region, and the Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE) model based on the presentation of allogeneic peptides derived from mismatched HLA, compared with the classical allele mismatch. Matching for both DPB1 alleles remains the best option to prevent acute GVHD. In the situation of one DPB1 allele mismatch, the donor associated with the lowest acute GVHD risks is mismatched for an allele with a low expression profile in the recipient, followed by a permissive TCE3/4 mismatch and/or the absence of PIRCHE II potential against the recipient. In the context of 2 DPB1 mismatches, the same considerations apply for a permissive TCE3/4 mismatch and no PIRCHE II. By combining the biological models, the most favorable DPB1 constellation can be defined. This approach will help optimize donor selection and improve post-HSCT complications and patient prognosis., (© 2021 by The American Society of Hematology.)
- Published
- 2021
- Full Text
- View/download PDF
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