Transplantation Conditioning

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William H. Krüger - One of the best experts on this subject based on the ideXlab platform.

  • Reduced platelet transfusions and earlier platelet engraftment using alemtuzumab-based Conditioning regimen in allogeneic stem cell Transplantation
    Journal of Cancer Research and Clinical Oncology, 2016
    Co-Authors: Thomas Neumann, Laila Schneidewind, Thomas Thiele, Meike Schulze, Anne F. Klenner, Christoph Busemann, Daniel Pink, Andreas Greinacher, Gottfried Dölken, William H. Krüger
    Abstract:

    Purpose In patients undergoing allogeneic stem cell Transplantation, Conditioning regimens containing alemtuzumab instead of anti-thymocyte globulin (ATG) may result in an earlier platelet engraftment and a reduced number of platelet transfusions. Methods We performed a retrospective, single-center, case–control study analyzing time to engraftment and transfusion needs using alemtuzumab in comparison with ATG as part of Conditioning protocol. Results Median values for time to platelet engraftment, number of transfused platelet concentrates and number of transfused red cell concentrates were 12 versus 19.5 days ( p  

Thomas Neumann - One of the best experts on this subject based on the ideXlab platform.

Cornelia Becker - One of the best experts on this subject based on the ideXlab platform.

  • Stem cell mobilization and autologous stem cell Transplantation after pretreatment with bendamustine, prednisone and bortezomib (BPV) in newly diagnosed multiple myeloma
    Journal of Cancer Research and Clinical Oncology, 2015
    Co-Authors: Wolfram Poenisch, Bruno Holzvogt, Marc Andrea, Thomas Zehrfeld, Doreen Hammerschmidt, Maik Schwarz, Thomas Edelmann, Madlen Plötze, Thomas Schliwa, Cornelia Becker
    Abstract:

    Introduction Reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell Transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing. Materials and methods A retrospective analysis of peripheral blood stem cell mobilization and autologous SCT was performed in 35 patients with MM who had received at least one cycle of a BPV-induction therapy consisting of bendamustine 60 mg/m^2 on days 1 and 2, bortezomib 1.3 mg/m^2 on days 1, 4, 8 and 11 and prednisone 100 mg on days 1, 2, 4, 8 and 11 between October 2008 and May 2014. The mobilization regimen consisted of cyclophosphamide 4 g/m^2 and G-CSF (2 × 5 μg/kg). Apheresis was started as soon as peripheral CD34^+ counts exceeded 20 × 10^6/L with a harvest target of 8 × 10^6 CD34^+/kg. The minimal accepted target was 2 × 10^6 CD34^+/kg. The Transplantation Conditioning therapy consisted of melphalan 200 mg/m^2. Results A median number of two (range 1–5) BPV cycles were given. The majority of patients ( n  = 31, 89 %) responded with two sCR, five nCR, 11 VGPR and 13 PR after BPV induction. Three patients had MR, and one SD. Stem cell mobilization and harvest were successful in all patients. In 19 of 35 patients (54 %), a single apheresis was sufficient to reach the target. The median number of aphereses was one (range 1–4), and the median CD34^+ cell-count/kg was 13.5 (range 3.2–33.1)  × 106. All patients received an autologous SCT. Engraftment was successful in 34 of 35 patients. The median time to a leukocyte count >l × 10^9/L was 11 days, and the time to untransfused platelet count of >50 × 10^9/L was 13 days. Thirty-four patients (97 %) responded after the autologous SCT with 11 sCR, two CR, seven nCR, seven VGPR and seven PR. The progression-free survival at 18 months was 87 %, and overall survival was 92 %. Conclusion Stem cell mobilization and autologous SCT are feasible in MM patients who have received BPV-induction therapy .

  • Successful Stem Cell Mobilization and Autologous Stem Cell Transplantation after Pretreatment Consisting of Bendamustine, Prednisone and Bortezomib (BPV) in 35 Patients with Newly Diagnosed/Untreated Multiple Myeloma
    Blood, 2014
    Co-Authors: Wolfram Poenisch, Madlen Ploetze, Bruno Holzvogt, Marc Andrea, Thomas Zehrfeld, Doreen Hammerschmidt, Maik Schwarz, Thomas Edelmann, Cornelia Becker, Hoffmann Fa
    Abstract:

    Introduction: Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks in DNA, and shows only partial cross resistance with other alkylating drugs. Treatment of patients with newly diagnosed multiple myeloma using Bendamustine and Prednisone in comparison to Melphalan and Prednisone results in superior complete response rate and prolonged time to treatment failure (Poenisch et al, Res Clin Oncol 132: 205-212;2006). So far, however, reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell Transplantation (SCT) after induction treatment with a combination of bendamustine, prednisone and bortezomib (BPV) is missing. Material and Methods: A retrospective analysis of peripheral blood stem cell mobilization and autologous SCT was performed in 35 patients with multiple myeloma who had received at least two cycles of a BPV induction therapy consisting of bendamustine 60 mg/m2 on days 1 and 2, bortezomib 1.3 mg/m² on days 1, 4, 8 and 11, and prednisone 100 mg on days 1, 2, 4, 8 and 11 between October 2008 and May 2014. The mobilization regimen consisted of cyclophosphamide 4 g/m2 and G-CSF (2x5µg/kg). Apheresis was started as soon as peripheral blood CD34+ counts exceeded 20x106/l with a harvest target of 8x106 CD34+/kg. The minimal accepted target was 2x106 CD34+/kg. Results: A median number of two (range 1–5) BPV treatment cycles were given to the patients. The majority of the patients (n = 31, 89 %) responded including 2 sCR, 5 nCR, 11 VGPR, and 13 PR. Three patients had MR, and 1 SD. Stem cell mobilization and harvest was successful in all patients. In 19 of 35 patients (54 %) a single apheresis was sufficient to reach the target. The median number of aphereses was one (range 1-4) and the median CD34+ cell-count/kg was 13.5 (range 3.2-33.1) x106. All patients received an autologous SCT. The pre-Transplantation Conditioning therapy consisted of melphalan 200 mg/m2. In 8 patients with concomitant heart amyloidosis or severe renal insufficiency melphalan dose was reduced to 100 or 140 mg/m2. Engraftment was successful in 34 of 35 patients. The median time to leucocytes count >l×109/l was reached after 11 (range 9–18) days and the time to untransfused platelet count of >50×109/l was 13 (range 10–55) days. 34 patients (97%) responded after the autologous SCT with 11 sCR, 2 CR, 7 nCR, 7 VGPR, and 7 PR. The progression free survival at 18 months was 87 % and overall survival was 92 %. Conclusion: Stem cell mobilization and autologous SCT is feasible in multiple myeloma patients who have received BPV induction therapy. Disclosures Al-Ali: Novartis: Consultancy, Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Lange: Novartis: Consultancy, Honoraria, Research Funding.

Claudio G. Brunstein - One of the best experts on this subject based on the ideXlab platform.

  • alternative donor Transplantation after reduced intensity Conditioning results of parallel phase 2 trials using partially hla mismatched related bone marrow or unrelated double umbilical cord blood grafts
    Blood, 2011
    Co-Authors: Claudio G. Brunstein, Ephraim J. Fuchs, Shelly L Carter, Chatchada Karanes, Luciano J Costa, Juan Wu, Steven M Devine, John R Wingard, Omar S Aljitawi, Corey Cutler
    Abstract:

    The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity Conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) Transplantation. For both trials, the Transplantation Conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB Transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow Transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow Transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow Transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB Transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow Transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603).

  • Negative effect of KIR alloreactivity in recipients of umbilical cord blood transplant depends on Transplantation Conditioning intensity.
    Blood, 2009
    Co-Authors: Claudio G. Brunstein, John E. Wagner, Daniel J. Weisdorf, Sarah Cooley, Harriet Noreen, Juliet N. Barker, Todd E. Defor, Michael R. Verneris, Bruce R. Blazar, Jeffrey S. Miller
    Abstract:

    We examined the clinical impact of killer-immunoglobulin receptor-ligand (KIR-L) mismatch in 257 recipients of single (n = 91) or double (n = 166) unit umbilical cord blood (UCB) grafts after myeloablative (n = 155) or reduced intensity (n = 102) Conditioning regimens. Analyses of double unit grafts considered the KIR-L match status of the dominant engrafting unit. After myeloablative Conditioning, KIR-L mismatch had no effect on grade III-IV acute graft-versus-host disease (GVHD), Transplantation-related mortality (TRM), relapse, and survival. In contrast, after reduced intensity Conditioning, KIR-L mismatch between the engrafted unit and the recipient resulted in significantly higher rates of grade III-IV acute GVHD (42% [CI, 27-59] vs 13% [CI, 5-21], P < .01) and TRM (27% [CI, 12%-42%] vs 12% [CI, 5%-19%], P = .03) with inferior survival (32% [CI, 15%-59%] vs 52% [CI, 47%-67%], P = .03). Multivariate analysis identified KIR-L mismatch as the only predictive factor associated with the development of grade III-IV acute GVHD (RR, 1.8 [CI, 1.1-2.9]; P = .02) and demonstrated a significant association between KIR-L mismatch and increased risk of death (RR, 1.8; 95% CI, 1.0-3.1; P = .05). Our results do not support the selection of UCB units based on KIR-L status and suggest that KIR-L mismatching should be avoided in reduced intensity UCB Transplantation.

  • Negative Effect of KIR Alloreactivity in Recipients of Umbilical Cord Blood Transplantation Depends on Transplantation Conditioning Intensity
    Blood, 2008
    Co-Authors: Claudio G. Brunstein, John E. Wagner, Daniel J. Weisdorf, Sarah Cooley, Harriet Noreen, Todd E. Defor, Michael R. Verneris, Juliet Barker, Philip B. Mcglave, Bruce R. Blazar
    Abstract:

    Abstract Transplant strategies involving natural killer (NK) cell alloreactivity (KIR-ligand mismatch [KIR-L mismatch]) have demonstrated superior outcomes for patients receiving T cell depleted HLA haploidentical hematopoietic stem cell allografts. It is unknown whether KIR-L mismatch has a similar effect in recipients of partially HLA-matched umbilical cord blood (UCB) grafts which contain comparatively few T-cells. We examined the clinical impact of KIR-L mismatch in 257 UCB recipients treated with either a myeloablative (n=155) or reduced intensity (n=102) regimen. After myeloablative Conditioning, KIR-L mismatch had no demonstrable effect on grades III–IV acute GVHD (17% [CI, 6–28%] vs. 17% [CI, 10–24], p=.97), transplant-related mortality (TRM) (27% [CI, 14–40%] vs. 18% [CI, 11–25%], p=.19), relapse at 2 yrs (18% [95%CI, 6–30%] vs. 28% [95%CI, 19–27%], p=.37) and survival at 3 yrs (50% [CI, 32–68%] vs. 57% [CI, 47–67%], p=.46). In contrast, following reduced intensity Conditioning when the engrafting unit was KIR-L mismatched there was a significantly higher incidence of grades III–IV acute GVHD (42% [CI, 27–59) vs. 13% [CI, 5–21], p &lt; .01). Multivariate analysis confirmed NK cell alloreactivity as the only predictive factor associated with severe acute GVHD was (RR 1.8, CI [1.1–2.9]; p=.02). TRM was higher (27% [CI, 12–42%] vs. 12% [CI, 5–19%], p=.03) and three year survival was poorer (32% [CI, 15–59%] vs. 52% [CI, 47–67%], p=.03) when the engrafting unit was KIR-L mismatched, but relapse was unaffected (39% [95%CI, 21–57%] vs. 47% [95%CI, 34–60%], p=.72). KIR-L mismatch in recipients of a RIC UCB transplant was associated with a significant increased risk of death (RR 1.8, 95%CI, 1.0–3.1, p=.05). This data identify divergent effects of NK cell alloreactivity which are unmasked when comparing myeloablative versus RIC transplant platforms. We conclude that KIR-L mismatch should be avoided in recipients of a reduced intensity UCB transplant.

Thomas Thiele - One of the best experts on this subject based on the ideXlab platform.

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