28 results on '"Bethge, W."'
Search Results
2. Ibrutinib for bridging to allogeneic hematopoietic stem cell transplantation (alloHCT) in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) is safe and effective: Updated results of a study by the EBMT Chronic Malignancy and Lymphoma Working Parties, the French Cooperative Group for CLL, and the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC)
- Author
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Dreger, P., Michallet, M., Bosman, P., Sobh, M., Boumendil, A., Nagler, A., Scheid, C., Cornelissen, J., Mueller, L., Niederwieser, D., Vandenberghe, E., Scortechini, I., Schoemans, H., Andersen, N., Finke, J., Russo, D., Ljungman, P., Passweg, J., van Gelder, M., Durakovic, N., Labussiere, H., Berg, T., Wulf, G., Bethge, W., Stilgenbauer, S., Mordini, N., Schaap, M., Fox, C., Kroeger, N., Montoto, S., Schetelig, J., Dreger, P., Michallet, M., Bosman, P., Sobh, M., Boumendil, A., Nagler, A., Scheid, C., Cornelissen, J., Mueller, L., Niederwieser, D., Vandenberghe, E., Scortechini, I., Schoemans, H., Andersen, N., Finke, J., Russo, D., Ljungman, P., Passweg, J., van Gelder, M., Durakovic, N., Labussiere, H., Berg, T., Wulf, G., Bethge, W., Stilgenbauer, S., Mordini, N., Schaap, M., Fox, C., Kroeger, N., Montoto, S., and Schetelig, J.
- Published
- 2017
3. RIC vs. MAC followed by allogeneic stem cell transplantation for patients with MDS or secondary AML: A prospective, randomized phase III study of the CMWP of the EBMT (RICMAC-Trial)
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Kroeger, N., Brand, R., Niederwieser, D., Platzbecker, U., Huebel, K., Weber, T., Robin, M., Stelljes, M., Afanasiev, B., Heim, D., Deliliers, G. Lambertenghi, Onida, F., Dreger, P., Pini, M., Guidi, S., Volin, L., Gramatzki, M., Bethge, W., Poire, X., Kobbe, G., van Os, M., Iacobelli, S., de Witte, T., Kroeger, N., Brand, R., Niederwieser, D., Platzbecker, U., Huebel, K., Weber, T., Robin, M., Stelljes, M., Afanasiev, B., Heim, D., Deliliers, G. Lambertenghi, Onida, F., Dreger, P., Pini, M., Guidi, S., Volin, L., Gramatzki, M., Bethge, W., Poire, X., Kobbe, G., van Os, M., Iacobelli, S., and de Witte, T.
- Published
- 2015
4. Allogeneic stem cell transplantation for MDS patients more than 70 years of age. A report of MDS subcommittee of CMWP of EBMT
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Heidenreich, S., Zabelina, T., van Biezen, A., Finke, J., Platzbecker, U., Niederwieser, D., Einsele, H., Bethge, W., Schwerdtfeger, R., Beelen, D., Tischer, J., Nagler, A., Zachee, P., Scheid, C., de Witte, T., Robin, M., Kroger, N., Heidenreich, S., Zabelina, T., van Biezen, A., Finke, J., Platzbecker, U., Niederwieser, D., Einsele, H., Bethge, W., Schwerdtfeger, R., Beelen, D., Tischer, J., Nagler, A., Zachee, P., Scheid, C., de Witte, T., Robin, M., and Kroger, N.
- Published
- 2015
5. Choice of commercially available CAR-T cell products for r/r DLBCL & PMBCL in Europe: a survey on behalf of the cellular therapy & immunobiology working party (CTIWP) of the EBMT.
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Novak U, Mooyaart JE, Daskalakis M, Scheid C, Gabellier L, Yakoub-Agha I, Ram R, Forcade E, López-Corral L, Nicholson E, Galli E, Stölzel F, Bethge W, Wagner-Drouet EM, Hoogenboom JD, Mielke S, Arber C, Simonetta F, Chabannon C, Kuball J, Ruggeri A, and Malard F
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- 2024
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6. Reduced intensity versus myeloablative conditioning for MDS: long-term results of an EBMT phase III study (RICMAC).
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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).)
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- 2024
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7. 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).
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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
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- 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.)
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- 2024
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8. Fludarabine-treosulfan versus fludarabine-melphalan or busulfan-cyclophosphamide conditioning in older AML or MDS patients - A clinical trial to registry data comparison.
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Beelen DW, Iacobelli S, Koster L, Eikema DJ, van Biezen A, Stölzel F, Ciceri F, Bethge W, Dreger P, Wagner-Drouet EM, Reményi P, Stelljes M, Markiewicz M, McLornan DP, Yakoub-Agha I, and Mohty M
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- Humans, Aged, Middle Aged, Female, Male, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Hematopoietic Stem Cell Transplantation methods, Busulfan analogs & derivatives, Busulfan therapeutic use, Busulfan administration & dosage, Busulfan pharmacology, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Vidarabine pharmacology, Vidarabine administration & dosage, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute mortality, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes drug therapy, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Cyclophosphamide pharmacology, Transplantation Conditioning methods, Registries, Melphalan therapeutic use, Melphalan administration & dosage, Melphalan pharmacology
- Abstract
A randomized study (acronym: MC-FludT.14/L Trial II) demonstrated that fludarabine plus treosulfan (30 g/m²) was an effective and well tolerated conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT) in older patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). To further evaluate this regimen, all 252 study patients aged 50 to 70 years were compared with similar patients, who underwent allo-HCT after fludarabine/melphalan (140 mg/m²) (FluMel) or busulfan (12.8 mg/kg)/cyclophosphamide (120 mg/kg) (BuCy) regimens and whose data was provided by the European Society for Blood and Marrow Transplantation registry. In 1:1 propensity-score matched-paired analysis (PSA) of AML patients, there was no difference in 2-year-relapse-incidence after FluTreo compared with either FluMel (n = 110, p = 0.28) or BuCy (n = 78, p = 0.98). However, 2-year-non-relapse-mortality (NRM) was lower compared with FluMel (p = 0.019) and BuCy (p < 0.001). Consequently, 2-year-overall-survival (OS) after FluTreo was higher compared with FluMel (p = 0.04) and BuCy (p < 0.001). For MDS patients, no endpoint differences between FluTreo and FluMel (n = 30) were evident, whereas 2-year-OS after FluTreo was higher compared with BuCy (n = 25, p = 0.01) due to lower 2-year-NRM. Multivariate sensitivity analysis confirmed all significant results of PSA. Consequently, FluTreo (30 g/m²) seems to retain efficacy compared with FluMel and BuCy, but is better tolerated by older patients., (© 2024. The Author(s).)
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- 2024
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9. Long-term outcome of second allogeneic hematopoietic stem cell transplantation (HSCT2) for primary graft failure in patients with acute leukemia in remission: A study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.
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Nagler A, Labopin M, Swoboda R, Kulagin A, Velardi A, Sanz J, Labussière-Wallet H, Potter V, Kuball J, Sica S, Parovichnikova E, Bethge W, Maillard N, Platzbecker U, Stölzel F, Ciceri F, and Mohty M
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- Humans, Adult, Bone Marrow, Retrospective Studies, Acute Disease, Transplantation Conditioning adverse effects, Leukemia, Myeloid, Acute therapy, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology
- Abstract
Second transplantation (HSCT2) is a potential treatment for primary graft failure (pGF). We assessed the outcome of HSCT2, performed between 2000 and 2021, for pGF in 243 patients with acute leukemia. Median age was 44.8 years. Conditioning at first HSCT (HSCT1) was myeloablative (MAC) in 58.4%. Median time from HSCT1 to HSCT2 was 48 days. Donors for HSCT2 were the same as for HSCT1 in 49%. Engraftment post HSCT2 was achieved by 73.7% of patients. The incidence of acute (a) graft versus host disease (GVHD) grades II-IV and III-IV was 23.2 and 8.1%. 5-year total and extensive chronic (c) GVHD was 22.3 and 10.1%. 5-year nonrelapse mortality (NRM), relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS) and GVHD free, relapse-free survival (GRFS) was 51.6, 18.8, 29.6, 30.7 and 22.4%, respectively. Infections were the main cause of death. In multivariable analysis, being transplanted at second vs. first remission, lower Karnofsky performance status (KPS; <90) and receiving MAC at HSCT1 were adverse prognostic factors for NRM, LFS, OS, and GRFS, as was increased age for NRM, LFS, OS. We conclude that HSCT2 can rescue about a third of the patients who experienced pGF, but NRM is as high as 50%., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2023
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10. Total body irradiation versus busulfan based intermediate intensity conditioning for stem cell transplantation in ALL patients >45 years-a registry-based study by the Acute Leukemia Working Party of the EBMT.
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Hirschbühl K, Labopin M, Polge E, Blaise D, Bourhis JH, Socié G, Forcade E, Yakoub-Agha I, Labussière-Wallet H, Bethge W, Chevallier P, Bonnet S, Stelljes M, Spyridonidis A, Peric Z, Brissot E, Savani B, Giebel S, Schmid C, Ciceri F, Nagler A, and Mohty M
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- Humans, Aged, Busulfan therapeutic use, Retrospective Studies, Whole-Body Irradiation, Stem Cell Transplantation, Acute Disease, Recurrence, Transplantation Conditioning methods, Registries, Leukemia, Myeloid, Acute therapy, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease
- Abstract
Allogeneic hematopoietic cell transplantation is a potentially curative treatment in high-risk acute lymphoblastic leukemia (ALL). Conditioning regimens based on ≥12 Gray total body irradiation (TBI) represent the current standard in patients ≤45 years, whereas elderly patients frequently receive intermediate intensity conditioning (IIC) to reduce toxicity. To evaluate the role of TBI as a backbone of IIC in ALL, a retrospective, registry-based study included patients >45 years transplanted from matched donors in first complete remission, who had received either fludarabine/TBI 8 Gy (FluTBI8, n = 262), or the most popular, irradiation-free alternative fludarabine/busulfan, comprising busulfan 6.4 mg/kg (FluBu6.4, n = 188) or 9.6 mg/kg (FluBu9.6, n = 51). At two years, overall survival (OS) was 68.5%, 57%, and 62.2%, leukemia-free survival (LFS) was 58%, 42.7%, and 45%, relapse incidence (RI) was 27.2%, 40%, and 30.9%, and non-relapse-mortality (NRM) was 23.1%, 20.7%, and 26.8% for patients receiving FluTBI8Gy, FluBu6.4, and FluBu9.6, respectively. In multivariate analysis, the risk of NRM, acute and chronic graft-versus-host disease was not influenced by conditioning. However, RI was higher after FluBu6.4 (hazard ratio [HR] [95% CI]: 1.85 [1.16-2.95]), and LFS was lower after both FluBu6.4 (HR: 1.56 [1.09-2.23]) and FluBu9.6 (HR: 1.63 [1.02-2.58]) as compared to FluTBI8. Although only resulting in a non-significant advantage in OS, this observation indicates a stronger anti-leukemic efficacy of TBI-based intermediate intensity conditioning., (© 2023. The Author(s).)
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- 2023
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11. Fludarabine/TBI 8 Gy versus fludarabine/treosulfan conditioning in patients with AML in first complete remission: a study from the Acute Leukemia Working Party of the EBMT.
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Bug G, Labopin M, Niittyvuopio R, Stelljes M, Reinhardt HC, Hilgendorf I, Kröger N, Kaare A, Bethge W, Schäfer-Eckart K, Verbeek M, Mielke S, Carlson K, Bazarbachi A, Spyridonidis A, Savani BN, Nagler A, and Mohty M
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- Humans, Adult, Middle Aged, Retrospective Studies, Whole-Body Irradiation, Busulfan pharmacology, Busulfan therapeutic use, Acute Disease, Vidarabine pharmacology, Vidarabine therapeutic use, Recurrence, Transplantation Conditioning, Leukemia, Myeloid, Acute therapy, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease
- Abstract
The optimal reduced intensity conditioning (RIC) regimen is a matter of debate. We retrospectively compared conditioning with fludarabine plus fractionated total body irradiation of 8 Gy (FluTBI) and fludarabine plus treosulfan 30, 36 or 42 g/m
2 (FluTreo) in 754 patients with AML above the age of 40 years undergoing an allogeneic hematopoietic stem cell transplant (HSCT) in first complete remission (CR). After balancing patient characteristics by propensity score matching of 115 patients in each group, FluTBI was associated with a significantly lower probability of relapse compared to FluTreo (18.3% vs. 34.7%, p = 0.018) which was counteracted by a higher non-relapse mortality (NRM, 16.8% vs. 5.3%, p = 0.02). Thus, overall survival and graft-versus-host disease-free and relapse-free survival at 2 years were similar between groups (OS 66.9% vs. 67.8%, GRFS 50.3% vs. 45.6%). Univariate analysis by age group demonstrated a higher NRM exclusively in patients ≥55 years of age treated with FluTBI compared to FluTreo (27.6% vs. 5.8%, p = 0.02), while a similarly low NRM was observed in patients <55 years in both groups (6.0% vs. 4.7%, p = ns). We conclude that both conditioning regimens are effective and safe, but FluTBI may better be reserved for younger patients below the age of 55 years., (© 2023. The Author(s).)- Published
- 2023
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12. Augmented FLAMSA-Bu versus FluBu2 reduced-intensity conditioning in patients with active relapsed/refractory acute myeloid leukemia: an EBMT analysis.
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Rodríguez-Arbolí E, Labopin M, Eder M, Brecht A, Blau IW, Huynh A, Forcade E, Tischer J, Bethge W, Bondarenko S, Verbeek M, Bulabois CE, Einsele H, Stölzel F, Savani B, Spyridonidis A, Bazarbachi A, Giebel S, Brissot E, Schmid C, Nagler A, and Mohty M
- Subjects
- Busulfan therapeutic use, Humans, Retrospective Studies, Transplantation Conditioning methods, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute
- Abstract
Comparative data of fludarabine, cytarabine and amsacrine (FLAMSA) chemotherapy followed by busulfan (Bu)-based reduced-intensity conditioning (RIC) (FLAMSA-Bu) versus RIC regimens are lacking in patients with active relapsed/refractory (R/R) acute myeloid leukemia (AML) at the time of allogeneic hematopoietic stem cell transplantation (alloSCT). Here, we retrospectively analyzed outcomes after FLAMSA-Bu versus fludarabine/busulfan (FluBu2) conditioning in this patient population. A total of 476 patients fulfilled the inclusion criteria, of whom 257 received FluBu2 and 219 FLAMSA-Bu. Median follow-up was 41 months. Two-year non-relapse mortality (21%), graft-versus-host disease-free, relapse-free survival (24%) and chronic graft-versus-host disease (GVHD) (29%) were not statistically different between cohorts. FLAMSA-Bu was associated with lower 2-year relapse incidence (RI) (38 vs 49% after FluBu2, p = 0.004), and increased leukemia-free survival (LFS) (42 vs 29%, p = 0.001), overall survival (47 vs 39%, p = 0.008) and grades II-IV acute GVHD (36 vs 20%, p = 0.001). In the multivariate analysis, FLAMSA-Bu remained associated with lower RI (HR 0.69, p = 0.042), increased LFS (HR 0.74, p = 0.048) and a higher risk of acute GVHD (HR 2.06, p = 0.005). Notwithstanding the limitations inherent in this analysis, our data indicate that FLAMSA-Bu constitutes a tolerable conditioning strategy, resulting in a long-term benefit in a subset of patients reaching alloSCT with active disease., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2022
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13. Ibrutinib as a salvage therapy after allogeneic HCT for chronic lymphocytic leukemia.
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Michallet M, Dreger P, Sobh M, Koster L, Hoek J, Boumendil A, Scheid C, Fox CP, Wulf G, Krüger W, van Gelder M, Corradini P, Russo D, Passweg J, Schoemans H, Bethge W, Schaap N, Cornelissen J, Browne P, Durakovic N, Muller L, Montoto S, Kroger N, and Schetelig J
- Subjects
- Adenine analogs & derivatives, Humans, Male, Piperidines, Retrospective Studies, Salvage Therapy, Hematopoietic Stem Cell Transplantation, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy
- Abstract
The purpose of our study is to provide information on safety and efficacy of ibrutinib as salvage treatment after allo-HSCT for CLL. A total of 56 patients were included, 36 (64%) males; median age at transplantation was 48 years (range: 35-64) and the median number of treatment lines prior to transplantation was 3 (1-10). The median time between allo-HSCT and Ibrutinib was 30 months (range: 1-140). Overall, 40 (71%) patients responded to Ibrutinib; 23 (41%) PR, and 17 (30%) CR. At time of ibrutinib initiation, ten patients had active chronic GVHD that resolved under Ibrutinib, whilst a single patient developed limited de novo chronic GVHD on Ibrutinib. Fourteen patients discontinued ibrutinib, four because of toxicity and ten because of disease progression. Overall, 14 patients progressed (median PFS = 24 months) among them 10 died. Two-year OS and PFS probabilities were 72% (95% CI: 52-84) and 50% (95% CI: 32-66), respectively. Patients with late relapse after allo-HSCT (≥24 months) had a better PFS after ibrutinib. Our study shows that ibrutinib can be safely administered for CLL relapse after allo-HSCT, with comparable efficacy to non-transplanted patients with high-risk disease.
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- 2020
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14. Retrospective single center analysis of outcome, risk factors and therapy in steroid refractory graft-versus-host disease after allogeneic hematopoietic cell transplantation.
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Axt L, Naumann A, Toennies J, Haen SP, Vogel W, Schneidawind D, Wirths S, Moehle R, Faul C, Kanz L, Axt S, and Bethge WA
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- Adult, Allografts, Female, Graft vs Host Disease etiology, Graft vs Host Disease pathology, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, TOR Serine-Threonine Kinases antagonists & inhibitors, Calcineurin Inhibitors administration & dosage, Graft vs Host Disease therapy, Hematopoietic Stem Cell Transplantation, Mycophenolic Acid administration & dosage, Photopheresis
- Abstract
Acute and chronic graft-vs.-host disease (aGvHD and cGvHD) are major complications after allogeneic hematopoietic cell transplantation (HCT) leading to substantial morbidity and mortality. This retrospective single-center study analyzes incidence, therapy, and outcome of GvHD in n = 721 patients ≥18 years having received allogeneic HCT 2004-2013 with a special focus on steroid refractory GvHD. Acute (n = 355/49.2%) and chronic (n = 269/37.3%) GvHD were mainly treated by steroids in first-line therapy. The proportion of steroid refractory aGvHD and cGvHD was 35.7% and 31.4%, respectively. As there is no standard therapy for steroid refractory GvHD, a range of different agents was used. In aGvHD, the overall response rate (ORR) of steroid refractory GvHD to second-line treatment was 27.4%. Mycophenolate mofetil (MMF) and mTOR inhibitors led to superior response rates (ORR 50.0% and 53.3%, respectively). In steroid refractory cGvHD therapy, ORR was 44.4%. Use of calcineurin inhibitors (CNI; n = 11/45.5%), MMF (n = 18/50.0%), mTOR inhibitors (n = 10/60.0%), and extracorporeal photophoresis (ECP; n = 16/56.3%) showed ORR above average. Targeted therapies lead to responses in 7.7% (n = 13). This data may help to improve the design of future prospective clinical studies in GvHD.
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- 2019
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15. Ibrutinib for bridging to allogeneic hematopoietic cell transplantation in patients with chronic lymphocytic leukemia or mantle cell lymphoma: a study by the EBMT Chronic Malignancies and Lymphoma Working Parties.
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Dreger P, Michallet M, Bosman P, Dietrich S, Sobh M, Boumendil A, Nagler A, Scheid C, Cornelissen J, Niederwieser D, Müller L, Vandenberghe E, Scortechini I, Schoemans H, Andersen NS, Finke J, Russo D, Ljungman P, Passweg J, van Gelder M, Durakovic N, Labussiere-Wallet H, Berg T, Wulf G, Bethge W, Bunjes D, Stilgenbauer S, Canepari ME, Schaap M, Fox CP, Kröger N, Montoto S, and Schetelig J
- Subjects
- Adenine analogs & derivatives, Adult, Aged, Allografts, Disease-Free Survival, Female, Humans, Male, Middle Aged, Piperidines, Survival Rate, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation, Leukemia, Lymphocytic, Chronic, B-Cell mortality, Leukemia, Lymphocytic, Chronic, B-Cell therapy, Lymphoma, Mantle-Cell mortality, Lymphoma, Mantle-Cell therapy, Pyrazoles administration & dosage, Pyrimidines administration & dosage
- Abstract
The aim of this retrospective study was to investigate the safety and efficacy of allogeneic hematopoietic cell transplantation (alloHCT) in patients pre-treated with ibrutinib. Eligible were patients aged >18 years allotransplanted for chronic lymphocytic leukemia (CLL) or mantle cell lymphoma (MCL) after prior exposure to ibrutinib who were registered with the EBMT registry. Seventy patients (CLL 48, MCL 22) were included. At the time of alloHCT, 73% of the patients were ibrutinib responsive. All patients except one engrafted, and acute GVHD grade 2-4 (3-4) was observed in 49% (12%) of 68 evaluable patients. The cumulative incidence of chronic GVHD was 54% 1 year after transplant. In the CLL group, 12-month non-relapse mortality, relapse incidence (RI), progression-free survival (PFS), and overall survival (OS) were 10, 30, 60, and 72%, respectively, and in the MCL group 5, 19, 76, and 86%, respectively. Pre-transplant ibrutinib failure and poor performance status predicted inferior RI, PFS and OS in the CLL group. In conclusion, ibrutinib does not affect the safety of a subsequent alloHCT. While the relatively high post-transplant relapse risk in ibrutinib-exposed patients with CLL deserves further study, in patients with MCL consolidating disease responses to ibrutinib with alloHCT seems to be a promising option.
- Published
- 2019
- Full Text
- View/download PDF
16. Association analysis between SUFU polymorphism rs17114808 and acute graft versus host disease after hematopoietic stem cell transplantation.
- Author
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Katz MC, Michaelis S, Siegmund DM, Koch R, Bethge W, Handgretinger R, and Mezger M
- Subjects
- Dendritic Cells, HLA-DR Antigens, Hematopoietic Stem Cell Transplantation, Humans, Nucleotides, Repressor Proteins, Down-Regulation, Graft vs Host Disease
- Published
- 2018
- Full Text
- View/download PDF
17. Allogeneic hematopoietic cell transplantation as curative therapy for non-transformed follicular lymphomas.
- Author
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Heinzelmann F, Bethge W, Beelen DW, Engelhard M, Kröger N, Dreger P, Niederwieser D, Finke J, Bunjes D, Tischer J, Kobbe G, Holler E, Bornhäuser M, Stelljes M, Baurmann H, Müller A, Haubitz I, Schrezenmeier H, Müller C, and Ottinger H
- Subjects
- Adolescent, Adult, Age Factors, Aged, Female, Germany, Graft vs Host Disease, Humans, Lymphoma, Follicular mortality, Male, Middle Aged, Prognosis, Registries, Salvage Therapy methods, Survival Rate, Tissue Donors, Transplantation Conditioning methods, Treatment Outcome, Whole-Body Irradiation, Young Adult, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Follicular therapy
- Abstract
Allogeneic hematopoietic cell transplantation (HCT) offers the chance of cure for patients with non-transformed follicular lymphoma (FL), but is associated with the risk of non-relapse mortality (NRM). The aim of this study was to identify subgroups of FL patients who benefit from HCT. The European Society for Blood and Marrow Transplantation (EBMT) Minimum-Essential-A Data of 146 consecutive patients who received HCT for FL between 1998 and 2008 were extracted from the database of the German Registry 'DRST'. Diagnosis of FL was verified by contact with the reference pathologists. Estimated 1-, 2- and 5-year overall survivals (OS) were 67%, 60% and 53%, respectively. Day 100 NRM was 15%. Thirteen out of 33 patients (40%) with treatment-refractory disease (RD) at the time of transplantation survived long term. Univariate statistical analysis suggested limited chronic GvHD, donor age ⩽42 years and TBI-based conditioning in treatment refractory patients to correlate with favorable OS. Independent prognostic factors for OS were treatment-sensitive disease and limited chronic GvHD for the whole cohort, and additionally TBI-based conditioning for the treatment refractory subgroup. In contrast, patient age ⩾55 years had no impact on outcome. Thus, HCT for FL is associated with acceptable NRM, and offers a substantial chance of cure for patients with RD or advanced age. Donors ⩽42 years should be preferred if available.
- Published
- 2016
- Full Text
- View/download PDF
18. Allogeneic stem cell transplantation after conditioning with treosulfan, etoposide and cyclophosphamide for patients with ALL: a phase II-study on behalf of the German Cooperative Transplant Study Group and ALL Study Group (GMALL).
- Author
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Kröger N, Bornhäuser M, Stelljes M, Pichlmeier U, Trenschel R, Schmid C, Arnold R, Martin H, Heinzelmann M, Wolschke C, Meyer RG, Bethge W, Kobbe G, Ayuk F, Gökbuget N, Hölzer D, Zander A, and Beelen D
- Subjects
- Adolescent, Adult, Allografts, Busulfan administration & dosage, Busulfan adverse effects, Busulfan analogs & derivatives, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Etoposide administration & dosage, Etoposide adverse effects, Female, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Humans, Male, Middle Aged, Myeloablative Agonists administration & dosage, Transplantation Conditioning adverse effects, Myeloablative Agonists adverse effects, Precursor Cell Lymphoblastic Leukemia-Lymphoma mortality, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Stem Cell Transplantation, Transplantation Conditioning methods
- Abstract
TBI-based preparative regimens are considered as standard conditioning therapy for allogeneic stem cell transplantation (AHSC) in patients with ALL. We investigated toxicity and efficacy of a non-TBI-based regimen consisting of treosulfan, etoposide and cyclophosphamide for ALL within a prospective study. Major inclusion criteria were CR and non-eligibility for TBI. Fifty patients with a median age of 46.5 years (range, 18-64) were included. Donors were HLA-identical sibling (n=8), matched (n=42) or mismatched (n=10) unrelated. The toxicity was moderate, resulting in a cumulative incidence of non-relapse mortality (NRM) at 1 year of 8% (90% confidence interval: 2-15%). Acute GvHD grade II-IV and grade III/IV was noted in 53% and 14%, respectively. Chronic GvHD at one year was seen in 41%. After a median follow-up of 24 months the cumulative incidence of relapse was 36% (90% confidence interval: 24-48) and 51% (90% confidence interval: 37-65) at 1 and 2 years, respectively. The estimated 2-year disease-free and overall survivals were 36 and 48%, respectively. Treosulfan, etoposide and cyclophosphamide followed by AHSC has a favorable toxicity profile with low NRM and therefore represents a potential alternative regimen for ALL in 1. CR (NCT00682305).
- Published
- 2015
- Full Text
- View/download PDF
19. Influence of age on outcome after allogeneic hematopoietic cell transplantation: a single center study in patients aged ⩾60.
- Author
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Federmann B, Faul C, Meisner C, Vogel W, Kanz L, and Bethge WA
- Subjects
- Age Factors, Aged, Female, Humans, Male, Middle Aged, Retrospective Studies, Transplantation Conditioning methods, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods
- Abstract
Reduced intensity conditioning regimens lead to an increasing use of allogeneic hematopoietic cell transplantation (HCT) in elderly patients. We retrospectively analyzed 151 patients aged ⩾60 receiving allogeneic HCT 2000-2012 at our center. Median age was 66 years. Kaplan-Meier estimated 3-year OS was 42% with a median follow-up of 38 months. Cumulative incidences of progression and non-relapse mortality after 3 years were 38 and 24%. OS was better in the group of patients >65 years with a Kaplan-Meier estimated OS of 50% vs 34%, P=0.060. We observed a significant influence of donor age (<50 years: 53% vs >50 years: 30%, P=0.017) and gender match (matched: 57% vs mismatched: 32%, P=0.007) on outcome. The use of a matched related donor was inferior compared with a matched or mismatched unrelated donor (19% vs 47%, P=0.015). On multivariate analysis there was an increased hazard ratio for a non-gender-matched HLA-matched-related donor (hazard ratio 3.23, 95% confidence interval 1.55-6.74, P=0.002). Age had no significant impact on OS (P=0.414). In conclusion, the data suggest that older age alone has no negative impact on the outcome of allogeneic HCT. Transplant decision should be tailored to disease risk and patient performance status rather than age.
- Published
- 2015
- Full Text
- View/download PDF
20. Extracorporeal photopheresis combined with pentostatin in the conditioning regimen for canine hematopoietic cell transplantation does not prevent GVHD.
- Author
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Bethge WA, Kerbauy FR, Santos EB, Gooley T, Storb R, and Sandmaier BM
- Subjects
- Animals, Dog Diseases prevention & control, Dogs, Flow Cytometry, Graft vs Host Disease prevention & control, Photopheresis methods, Transplantation Chimera, Antineoplastic Agents pharmacology, Dog Diseases therapy, Graft vs Host Disease veterinary, Hematopoietic Stem Cell Transplantation methods, Pentostatin pharmacology, Photopheresis veterinary, Transplantation Conditioning methods
- Abstract
Extracorporeal photopheresis (ECP) and the purine analog pentostatin exert potent immunomodulatory effects. We evaluated the use of these treatment modalities to prevent GVHD in a canine model of unrelated dog leukocyte Ag-mismatched hematopoietic cell transplantation, after conditioning with 920 cGy TBI. We have shown previously in this model that 36/40 dogs given MTX alone as postgrafting immunosuppression engrafted and that 25 of 40 dogs had severe GVHD and median survival of 21 days. In the current study, nine dogs received conditioning with 920 cGy TBI and postgrafting MTX either with ECP on days -2 to -1 alone (n=5) or ECP on days -6 and -5 combined with two doses of pentostatin (days -4 to -3) (n=4). Seven of nine dogs achieved engraftment. Six dogs developed severe acute GVHD (four in the group with ECP alone and two with pentostatin and ECP). We failed to demonstrate a positive impact of ECP and pentostatin for the prevention of GVHD compared with historical control dogs.
- Published
- 2014
- Full Text
- View/download PDF
21. Extracorporeal photopheresis increases neutrophilic myeloid-derived suppressor cells in patients with GvHD.
- Author
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Rieber N, Wecker I, Neri D, Fuchs K, Schäfer I, Brand A, Pfeiffer M, Lang P, Bethge W, Amon O, Handgretinger R, and Hartl D
- Subjects
- Adolescent, Adult, Age Factors, Aged, Case-Control Studies, Cells, Cultured, Child, Child, Preschool, Chronic Disease, Female, Graft vs Host Disease blood, Graft vs Host Disease immunology, Graft vs Host Disease pathology, Humans, Male, Middle Aged, Myeloid Cells pathology, Neutrophils pathology, Young Adult, Graft vs Host Disease therapy, Myeloid Cells immunology, Neutrophils immunology, Photopheresis methods
- Abstract
Extracorporeal photopheresis (ECP) is beneficial in patients with T-cell-mediated disorders, including GvHD, but the underlying immunological mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their capacity to suppress T-cell proliferation. We quantified MDSCs by flow cytometry in peripheral blood from patients after BMT with GvHD before and after ECP treatment, patients after BMT but without GvHD and age-matched healthy controls. MDSC functionality was analyzed using T-cell proliferation, cytokine release and arginase activity. GvHD patients showed increased baseline percentages of neutrophilic MDSCs (PMN-MDSCs) compared with healthy controls and patients after BMT without GvHD. ECP treatment in GvHD patients rapidly increased circulating percentages of PMN-MDSCs. Functionally, PMN-MDSCs efficiently dampened Th1 and Th17 responses and were paralleled by an increase of cellular and extracellular arginase activity. Following ECP longitudinally over 16 weeks, two GvHD responder subgroups were identified, with group one continuously increasing PMN-MDSCs and group two with stable or decreasing PMN-MDSCs over time. This study demonstrates for the first time that ECP increases T-cell-dampening PMN-MDSCs in GvHD patients, a finding that should be confirmed in larger series of GvHD patients.
- Published
- 2014
- Full Text
- View/download PDF
22. Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma.
- Author
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Bethge WA, von Harsdorf S, Bornhauser M, Federmann B, Stelljes M, Trenschel R, Baurmann H, Dittmann H, Faul C, Vogel W, Kanz L, and Bunjes D
- Subjects
- Adult, Aged, Alemtuzumab, Antibodies, Monoclonal, Humanized administration & dosage, Cyclosporine therapeutic use, Dose-Response Relationship, Radiation, Female, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin surgery, Male, Melphalan administration & dosage, Middle Aged, Neoplasm Grading, Prognosis, Prospective Studies, Radioimmunotherapy adverse effects, Radiopharmaceuticals therapeutic use, Transplantation Conditioning adverse effects, Transplantation, Homologous, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Antibodies, Monoclonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Non-Hodgkin radiotherapy, Radioimmunotherapy methods, Transplantation Conditioning methods, Yttrium Radioisotopes therapeutic use
- Abstract
A total of 20 patients enrolled in a multicenter phase II dose escalation study of radioimmunotherapy (RIT) using yttrium-90-ibritumomab tiuxetan at two dose levels (22 and 30 MBq/kg) in 10 patients, combined with reduced intensity conditioning (RIC) using fludarabine, melphalan and alemtuzumab followed by allogeneic hematopoietic cell transplantation (HCT) from either matched-related (n=5) or matched-unrelated donors (n=15). Postgrafting immunosuppression with cyclosporine was administered. Diagnoses were diffuse large B-cell lymphoma (n=13), transformed CLL (n=4), blastic mantle cell lymphoma (n=2) and follicular lymphoma grade 3 (n=1). Median age was 51 (range, 29-69) years. All patients were high risk with relapsed/refractory disease or relapse after preceding autologous HCT. Median follow-up of patients alive was 1115 (range, 1006-1252) days. No directly RIT-related toxicities were observed. The cumulative incidence of non-relapse mortality was 30%. Incidences of grade II-IV acute and chronic GvHD was 45% and 70%, respectively. Kaplan-Meier estimated 3-year OS and EFS were 20% for both dose levels. In conclusion, dose escalation of RIT and combined use with RIC is feasible with no additional toxicity due to dose escalation. This study is registered on http://clinicaltrials.gov as NCT00302757.
- Published
- 2012
- Full Text
- View/download PDF
23. Extracorporeal photopheresis in addition to pentostatin in conditioning for canine hematopoietic cell transplantation: role in engraftment.
- Author
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Bethge WA, Kerbauy FR, Santos E, Gooley TA, Storb R, and Sandmaier BM
- Subjects
- Animals, Dogs, Histocompatibility Antigens immunology, Immunomodulation, Transplantation, Homologous, Hematopoietic Stem Cell Transplantation methods, Pentostatin pharmacology, Photopheresis, Transplantation Conditioning methods
- Abstract
Extracorporeal photopheresis (ECP) and the purine analog pentostatin exert potent immunomodulatory effects, but have not been evaluated for their ability to enhance engraftment of hematopoietic stem cells. We evaluated, in a canine model of dog leukocyte antigen (DLA)-identical hematopoietic cell transplantation (HCT), whether ECP in combination with pentostatin could enhance engraftment using a nonmyeloablative regimen consisting of 100 cGy TBI and postgrafting immunosuppression with mycophenolate mofetil and CYA. We have shown previously that with 100 cGy TBI alone as conditioning, all of the six dogs rejected their grafts 2-12 weeks after HCT. With the addition of pentostatin to 100 cGy TBI, 6 of 10 dogs rejected their graft. We now tested the additional use of ECP alone (n=2) or ECP and 3-6 doses of pentostatin (n=7) before 100 cGy TBI and HCT. Eight out of nine dogs rejected their grafts within 6-11 weeks after HCT. Compared with data without ECP, we failed to demonstrate a positive impact of the use of either ECP or pentostatin for prevention of rejection.
- Published
- 2011
- Full Text
- View/download PDF
24. Cervical fascial and muscular involvement in chronic GVHD after allo-SCT and radiation therapy.
- Author
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Sauter A, Bethge W, Vogel U, and Horger M
- Subjects
- Antineoplastic Combined Chemotherapy Protocols, Fasciitis pathology, Fasciitis therapy, Humans, Lymphoma, Follicular radiotherapy, Male, Middle Aged, Myositis pathology, Myositis therapy, Neck radiation effects, Neck Pain etiology, Radiotherapy adverse effects, Fasciitis etiology, Graft vs Host Disease complications, Lymphoma, Follicular therapy, Myositis etiology, Stem Cell Transplantation adverse effects
- Published
- 2009
- Full Text
- View/download PDF
25. Current status and future perspectives for yttrium-90 ((90)Y)-ibritumomab tiuxetan in stem cell transplantation for non-Hodgkin's lymphoma.
- Author
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Gisselbrecht C, Bethge W, Duarte RF, Gianni AM, Glass B, Haioun C, Martinelli G, Nagler A, Pettengell R, Sureda A, Tilly H, and Wilson K
- Subjects
- Hematopoietic Stem Cell Transplantation methods, Humans, Immunotherapy methods, Transplantation Conditioning methods, Transplantation, Autologous, Transplantation, Homologous, Antibodies, Monoclonal therapeutic use, Lymphoma, Non-Hodgkin therapy, Myeloablative Agonists therapeutic use
- Abstract
Haematopoietic SCT is currently considered a therapeutic option mainly in relapsed or refractory non-Hodgkin's lymphoma (NHL) owing to high post-transplantation relapse rates and significant toxicity of conventional myeloablative conditioning for allogeneic SCT. Radiolabelled immunotherapy combines the benefits of monoclonal antibody targeting with therapeutic doses of radiation, and is a promising advance in the treatment of malignant lymphomas. It is now under investigation as a component of conditioning prior to SCT, with the aim of improving outcomes following SCT without increasing the toxicity of high-dose chemotherapy pre-transplant conditioning. An expert panel met at a European workshop in November 2006 to review the latest data on radiolabelled immunotherapy in the transplant setting, and its potential future directions, with a focus on (90)Y-ibritumomab tiuxetan. They reviewed data on the combination of standard/high/escalating dose (90)Y-ibritumomab tiuxetan with high-dose chemotherapy, and high/escalating dose (90)Y-ibritumomab tiuxetan as the sole myeloablative agent, prior to autologous SCT, and also (90)Y-ibritumomab tiuxetan as a component of reduced intensity conditioning prior to allogeneic SCT. The preliminary data are highly promising in terms of conditioning tolerability and patient outcomes following transplant; further phase II studies are now needed to consolidate these data and to investigate specific patient populations and NHL subtypes.
- Published
- 2007
- Full Text
- View/download PDF
26. Flow cytometry with anti HLA-antibodies: a simple but highly sensitive method for monitoring chimerism and minimal residual disease after HLA-mismatched stem cell transplantation.
- Author
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Schumm M, Feuchtinger T, Pfeiffer M, Hoelle W, Bethge W, Ebinger M, Kuci S, Handgretinger R, and Lang P
- Subjects
- Female, HLA Antigens genetics, Haplotypes, Histocompatibility Testing, Humans, Male, Neoplasm, Residual immunology, Sensitivity and Specificity, T-Lymphocytes immunology, Transplantation Chimera genetics, Antibodies, Monoclonal, Flow Cytometry methods, HLA Antigens immunology, Neoplasm, Residual diagnosis, Stem Cell Transplantation adverse effects, Transplantation Chimera immunology
- Abstract
Transplantation of HLA-mismatched stem cells may allow determination of chimerism status of single cells by differential expression of HLA molecules. Monoclonal antibodies against HLA antigens can be used to determine the HLA type of sub-populations by standard flow cytometry. Blood samples from 23 patients transplanted from HLA-mismatched family donors were monitored using HLA-specific antibodies. Suitable antibodies could be found for all donor recipient pairs by using differences in HLA Bw4 and Bw6 groups or other serological antigens. Pretransplant controls of donor and recipient were used to correct for variable fluorescence intensities of the antibodies and sub-populations. Owing to the high sensitivity, cell populations with a minimum frequency of 0.1% were detectable. Flow-cytometric analysis was confirmed by chimerism analysis of immunomagnetically isolated T cells by standard PCR technique. In addition to chimerism evaluation, HLA antibodies improved the detection of leukemic cells after transplantation with aberrant phenotype. In conclusion, flow cytometry using antibodies against HLA antigens is an interesting tool for determination of chimerism and minimal residual disease after HLA-mismatched transplantation. Information about the chimerism status is given on a single-cell level and allows fast and convenient analysis of sub-populations.
- Published
- 2007
- Full Text
- View/download PDF
27. Serious graft-versus-host disease after hematopoietic cell transplantation following nonmyeloablative conditioning.
- Author
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Flowers ME, Traina F, Storer B, Maris M, Bethge WA, Carpenter P, Appelbaum F, Storb R, Sandmaier BM, and Martin PJ
- Subjects
- Activities of Daily Living, Adolescent, Adult, Cause of Death, Child, Child, Preschool, Female, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation methods, Hospitalization, Humans, Incidence, Infections, Male, Middle Aged, Retrospective Studies, Severity of Illness Index, Suicide, Transplantation Conditioning methods, Graft vs Host Disease epidemiology, Hematopoietic Stem Cell Transplantation adverse effects, Transplantation Conditioning adverse effects
- Abstract
The efficacy of allogeneic hematopoietic cell transplantation (HCT) after nonmyeloablative conditioning depends on the balance between the desirable antineoplastic effects of donor cells weighed against the undesirable morbidity of graft-versus-host disease (GVHD). Development of serious acute or chronic GVHD was analyzed retrospectively in 171 consecutive patients, who had related or unrelated nonmyeloablative HCT for hematologic malignancies. GVHD was defined as serious when it resulted in (1) death, (2) disability, (3) three or more major infections in 1 year, (4) prolonged hospitalization or (5) suicide or hospitalization for suicidal ideation. According to this definition, 43 of 171 (25%) patients developed serious GVHD with a median follow-up of 30 (range, 12-65) months. The incidence of serious GVHD was similar after related and unrelated HCT. Among the 43 patients with serious GVHD, 20 had grade III-IV acute GVHD, and 30 had extensive chronic GVHD. Among the 171 patients, seven had grade III acute GVHD and 84 had extensive chronic GVHD that did not meet criteria for serious GVHD. Assessment of serious GVHD provides additional useful information to acute GVHD grades and classification of limited and extensive chronic GVHD in describing the overall risk and impact complications caused by donor cells.
- Published
- 2005
- Full Text
- View/download PDF
28. Successful treatment of human herpesvirus-6 encephalitis after bone marrow transplantation.
- Author
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Bethge W, Beck R, Jahn G, Mundinger P, Kanz L, and Einsele H
- Subjects
- Adult, Combined Modality Therapy, DNA, Viral cerebrospinal fluid, Encephalitis, Viral etiology, Encephalitis, Viral therapy, Female, Foscarnet administration & dosage, Herpesviridae Infections etiology, Herpesviridae Infections therapy, Humans, Male, Middle Aged, Polymerase Chain Reaction, Bone Marrow Transplantation, Encephalitis, Viral diagnosis, Herpesviridae Infections diagnosis, Herpesvirus 6, Human genetics
- Abstract
We report two cases of human herpesvirus-6 (HHV-6)-associated encephalitis in patients after BMT. Both patients reported distinct neurological symptoms with disorientation, sleepiness and loss of short-term memory. Diagnosis was based on PCR analysis of the cerebrospinal fluid (CSF) positive for HHV-6 variant B-DNA. After institution of therapy with foscarnet in both cases, neurological symptoms improved and in one patient clearance of HHV-6-DNA from CSF was demonstrated. These cases show that HHV-6 infection has to be considered in patients with neurological symptoms following BMT and effective treatment of HHV-6 encephalitis is possible if instituted early.
- Published
- 1999
- Full Text
- View/download PDF
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