Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: A retrospective analysis on 32 patients

Milpied, Noël; Vasseur, B.; Parquet, Nathalie; Garnier, J. L.; Antoine, Corinne; Quartier, Pierre; Carret, Anne‐Sophie; Bouscary, Didier; Faye, Albert; Bourbigot, B.; Réguerre, Yves; Stoppa, Anne‐Marie; Bourquard, Pascal; Ligny, Bruno Hurault de; Dubief, F. D.; Mathieu-Boué, Anne; Leblond, Véronique

doi:10.1093/annonc/11.suppl_1.s113

Cited by 283 publications

(211 citation statements)

References 14 publications

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“…This is consistent with published reports of the response rates to rituximab. [29][30][31][32] Administration of rabbit-anti-human T lymphocyte antibodies has been increasingly used by transplant programs because the antibodies can partially prevent aGVHD and cGVHD without impacting rates of relapse and non-EBV infections (except when used at a high dose, for example, 48 mg/kg thymoglobulin). 9,20,[33][34][35][36][37][38][39][40][41] Thus, our findings that in patients conditioned with rabbit-ATG, the PTLD occurrence is relatively high (8.1%) and that the vast majority of PTLD's occurring before day 100 are important.…”

Section: Discussionmentioning

confidence: 99%

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Hoegh-Petersen

Goodyear

Geddes

et al. 2010

Bone Marrow Transplant

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The largest study on post-allogeneic hematopoietic cell transplant lymphoproliferative disorder (PTLD) epidemiology showed a cumulative incidence of 1.7% in patients receiving antithymocyte globulin (ATG). We had noted an apparently higher incidence in our transplant recipients whose conditioning included ATG. Therefore, we formally determined the incidence of PTLD through chart review. We also evaluated whether counts of EBV-specific T lymphocytes measured by cytokine flow cytometry could identify patients at risk of developing PTLD. Among 307 allogeneic transplant recipients, 25 (8.1%) developed PTLD. This was biopsy proven in 11 patients, and was fatal in seven patients. Patient age, EBV serostatus, donor type/match or GVHD did not influence PTLD risk significantly. Median onset of PTLD was 55 (range, 28-770) days post transplant. Day 28 EBV-specific T lymphocyte counts were not significantly different in 11 patients who developed PTLD and 31 non-PTLD patients matched for published risk factors for PTLD. In summary, when using conditioning with thymoglobulin 4.5 mg/kg, the incidence of PTLD is relatively high and cannot be predicted by day 28 cytokine flow cytometry-determined EBV-specific T lymphocyte counts. Thus, in this scenario PTLD prevention may be warranted, for example, using EBV DNAemia monitoring with preemptive therapy.

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Section: Discussionmentioning

confidence: 99%

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Hoegh-Petersen

Goodyear

Geddes

et al. 2010

Bone Marrow Transplant

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“…Few phase II studies exist for Burkitt's lymphoma: results regarding response and relapse seems good but it is difficult to know the improvement secondary to rituximab use (Thomas et al, 2006). In post-transplant lymphoproliferative disease several phase II have shown a good activity with rituximab alone or in combination with chemotherapy (Milpied et al, 2000;Blaes et al, 2005;Jain et al, 2005).…”

Section: Other Lymphomasmentioning

confidence: 99%

Rituximab therapy in malignant lymphoma

2007

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“…Although several effector mechanisms seem to be triggered by Rituximab, 50% of NHL-patients do not respond. Recently, also patients with CD20-positive post-transplantation lymphoproliferative disorder (PTLD) were treated with Rituximab and also in this group 30% of the patients did not respond (Milpied et al, 2000). Various escape mechanisms which cause this non-responsiveness can be envisaged (e.g.…”

Section: Discussionmentioning

confidence: 99%

Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells

et al. 2001

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This paper describes a bi-specific antibody, which was called BIS20x3. It retargets CD3ɛ-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid–hybridoma fusion. BIS20x3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20x3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20x3 on T-cells using cross-linking F(ab′)2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20x3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20x3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20x3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/ Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/ Fas L, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Humanized anti-CD20 monoclonal antibody (Rituximab) in post transplant B-lymphoproliferative disorder: A retrospective analysis on 32 patients

Cited by 283 publications

References 14 publications

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

High incidence of post transplant lymphoproliferative disorder after antithymocyte globulin-based conditioning and ineffective prediction by day 28 EBV-specific T lymphocyte counts

Rituximab therapy in malignant lymphoma

Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells

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