5 results on '"Kuball, Jurgen"'
Search Results
2. Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients.
- Author
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Bethge WA, Eyrich M, Mielke S, Meisel R, Niederwieser D, Schlegel PG, Schulz A, Greil J, Bunjes D, Brecht A, Kuball J, Schumm M, Vucinic V, Wiesneth M, Bonig H, Westinga K, Biedermann S, Holtkamp S, Karitzky S, Malchow M, Siewert C, Handgretinger R, and Lang P
- Subjects
- Adult, Antigens, CD19, Child, Humans, Lymphocyte Depletion methods, Prospective Studies, Receptors, Antigen, T-Cell, alpha-beta, Transplantation Conditioning methods, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute therapy
- Abstract
Hematopoietic stem cell transplantation (HSCT) from haploidentical donors is a viable option for patients lacking HLA-matched donors. Here we report the results of a prospective multicenter phase I/II trial of transplantation of TCRαβ and CD19-depleted peripheral blood stem cells from haploidentical family donors after a reduced-intensity conditioning with fludarabine, thiotepa, and melphalan. Thirty pediatric and 30 adult patients with acute leukemia (n = 43), myelodysplastic or myeloproliferative syndrome (n = 6), multiple myeloma (n = 1), solid tumors (n = 6), and non-malignant disorders (n = 4) were enrolled. TCR αβ/CD19-depleted grafts prepared decentrally at six manufacturing sites contained a median of 12.1 × 10
6 CD34+ cells/kg and 14.2 × 103 TCRαβ+ T-cells/kg. None of the patients developed grade lll/IV acute graft-versus-host disease (GVHD) and only six patients (10%) had grade II acute GVHD. With a median follow-up of 733 days 36/60 patients are alive. The cumulative incidence of non-relapse mortality at day 100, 1 and 2 years after HSCT was 5%, 15%, and 17% for all patients, respectively. Estimated probabilities of overall and disease-free survival at 2 years were 63% and 50%, respectively. Based on these promising results in a high-risk patient cohort, haploidentical HSCT using TCRαβ/CD19-depleted grafts represents a viable treatment option., (© 2021. The Author(s).)- Published
- 2022
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3. Comparison of reduced-intensity conditioning regimens in patients with acute lymphoblastic leukemia >45 years undergoing allogeneic stem cell transplantation-a retrospective study by the Acute Leukemia Working Party of EBMT.
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Peric Z, Labopin M, Peczynski C, Polge E, Cornelissen J, Carpenter B, Potter M, Malladi R, Byrne J, Schouten H, Fegueux N, Socié G, Rovira M, Kuball J, Gilleece M, Giebel S, Nagler A, and Mohty M
- Subjects
- Busulfan, Humans, Retrospective Studies, Survival Analysis, Transplantation Conditioning, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
The optimal reduced-intensity conditioning (RIC) for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively analyzed 417 patients > 45 years with ALL in first complete remission who underwent a matched sibling or unrelated allo-HSCT and compared outcomes between fludarabine/busulfan (FLUBU, n = 127), fludarabine/melphalan (FLUMEL, n = 190), and fludarabine-TBI (FLUTBI, n = 100) conditioning. At 2 years, there were no differences between the groups in terms of cumulative incidence (CI) of relapse (40% for FLUBU vs 36% for FLUMEL vs 41% for FLUTBI, p = 0.21); transplant-related mortality (TRM) (18% for FLUBU, 22% for FLUMEL, 14% for FLUTBI, p = 0.09); overall survival (55% for FLUBU, 50% for FLUMEL, 60% for FLUTBI, p = 0.62) or leukemia-free survival (43% for FLUBU, 42% for FLUMEL, 45% for FLUTBI, p = 0.99), but GVHD-relapse-free survival was significantly lower in the FLUTBI group than FLUBU and FLUMEL group (18% vs 35% vs 28%, p = 0.02). However, this difference was lost in the multivariate analysis when adjusted for the in vivo T-cell depletion. Finally, the FLUMEL regimen was shown to be an independent risk factor for a higher TRM (HR 1.97, 95% CI 1.05-3.72, p = 0.04). We conclude that the three most popular RIC regimens yield similar transplant outcomes.
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- 2020
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4. Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.
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Eder S, Labopin M, Arcese W, Or R, Majolino I, Bacigalupo A, de Rosa G, Volin L, Beelen D, Veelken H, Schaap NP, Kuball J, Cornelissen J, Nagler A, and Mohty M
- Subjects
- Adolescent, Adult, Aged, Cyclophosphamide administration & dosage, Disease-Free Survival, Humans, Incidence, Middle Aged, Siblings, Survival Rate, Unrelated Donors, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Thiotepa administration & dosage, Transplantation Conditioning methods, Whole-Body Irradiation
- Abstract
Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2016
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5. Association between anti-thymocyte globulin exposure and survival outcomes in adult unrelated haemopoietic cell transplantation: a retrospective, pharmacodynamic cohort analysis
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Admiraal, Rick, Nierkens, Stefan, de Witte, Moniek A, Petersen, Eefke J, Fleurke, Ger-Jan, Verrest, Luka, Belitser, S., Bredius, Robbert G M, Raymakers, Reinier A P, Knibbe, Catherijne A J, Minnema, Monique C, Van Kesteren, Charlotte, Kuball, Jurgen, Boelens, Jaap J, Sub Pharmacotherapy, Theoretical, and Pharmacoepidemiology and Clinical Pharmacology
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Adult ,Male ,medicine.medical_specialty ,Population ,Graft vs Host Disease ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Humans ,Medicine ,Dosing ,education ,Antilymphocyte Serum ,Retrospective Studies ,education.field_of_study ,Thymoglobulin ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Area under the curve ,Retrospective cohort study ,Hematology ,Anti-thymocyte globulin ,Transplantation ,Leukemia, Myeloid, Acute ,Treatment Outcome ,Myelodysplastic Syndromes ,030220 oncology & carcinogenesis ,Immunology ,Female ,business ,030215 immunology - Abstract
Summary Background Anti-thymocyte globulin (ATG) is used to prevent graft-versus-host disease (GvHD) after allogeneic haemopoietic cell transplantation (HCT). However, ATG can also cause delayed immune reconstitution of T cells, negatively affecting survival. We studied the relation between exposure to ATG and clinical outcomes in adult patients with acute leukaemia and myelodysplastic syndrome. Methods We did a retrospective, pharmacokinetic-pharmacodynamic analysis of data from patients with acute lymphoid leukaemia, acute myeloid leukaemia, or myelodysplastic syndrome receiving their first T-cell repleted allogeneic peripheral blood stem cell HCT with ATG (thymoglobulin) as part of non-myeloablative conditioning from March 1, 2004, to June 1, 2015. Patients received a cumulative intravenous dose of 8 mg/kg divided over 4 days, starting on day −8 before HCT. Active ATG concentrations were measured using a validated bioassay and pharmacokinetic exposure measures (maximum concentration, concentration at time of infusion of the graft, time to reach a concentration of 1 arbitary unit [AU] per day/mL, area under the curve [AUC], and the AUC before and after HCT) were calculated with a validated population pharmacokinetic model. The main outcome of interest was 5-year overall survival, defined as days to death from any cause or last follow-up. Other outcomes were relapse-related mortality, non-relapse mortality, event-free survival, acute and chronic GvHD, and assessment of current and optimum dosing. We used Cox proportional hazard models and Fine-Gray competing risk models for the analyses. Findings 146 patients were included. ATG exposure after HCT was shown to be the best predictor for 5-year overall survival. Optimum exposure after transplantation was determined to be 60–95 AU per day/mL. Estimated 5-year overall survival in the group who had optimum exposure (69%, 95% CI 55–86) was significantly higher than in the group who had below optimum exposure (32%, 20–51, p=0·00037; hazard ratio [HR] 2·41, 95% CI 1·15–5·06, p=0·020) and above optimum exposure (48%, 37–62, p=0·030; HR 2·11, 95% CI 1·04–4·27, p=0·038). Patients in the optimum exposure group had a greater chance of event-free survival than those in the below optimum exposure group (HR 2·54, 95% CI 1·29–5·00, p=0·007; HR for the above optimum group: 1·83, 0·97–3·47, p=0·063). Above-optimum exposure led to higher relapse-related mortality compared with optimum exposure (HR 2·66, 95% CI 1·12–6·31; p=0·027). Below optimum exposure increased non-relapse mortality compared with optimum exposure (HR 4·36, 95% CI 1·60–11·88; p=0·0040), grade 3–4 acute GvHD (3·09, 1·12–8·53; p=0·029), but not chronic GvHD (2·38, 0·93–6·08; p=0·070). Modelled dosing based on absolute lymphocyte counts led to higher optimum target attainment than did weight-based dosing. Interpretation Exposure to ATG affects survival after HCT in adults, stressing the importance of optimum ATG dosing. Individualised dosing of ATG, based on lymphocyte counts rather than bodyweight, might improve survival chances after HCT. Funding Netherlands Organization for Health Research and Development and Queen Wilhelma Fund for Cancer Research.
- Published
- 2017
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