Addition of treosulfan to a nonmyeloablative conditioning regimen results in enhanced chimerism and immunologic tolerance in an experimental allogeneic.

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Presentation transcript:

Addition of treosulfan to a nonmyeloablative conditioning regimen results in enhanced chimerism and immunologic tolerance in an experimental allogeneic bone marrow transplant model Rob E Ploemacher, Kevin W Johnson, Elwin J.C Rombouts, Kenol Etienne, G.Robbin Westerhof, Joachim Baumgart, Mary E White- Scharf, Julian D Down Biology of Blood and Marrow Transplantation Volume 10, Issue 4, Pages 236-245 (April 2004) DOI: 10.1016/j.bbmt.2003.11.004

Figure 1 A, Double-exposure simulation radiograph showing the positioning of the thymic irradiation (TI) fields. B, Treatment and transplantation protocols using nonmyeloablative BMT conditioning with treosulfan (TR), fludarabine (FL), TI, and T cell-depleting antibodies (CD4/CD8 ). Either skin grafting or DLI was performed at 10 weeks after BMT. Biology of Blood and Marrow Transplantation 2004 10, 236-245DOI: (10.1016/j.bbmt.2003.11.004)

Figure 2 Percentage survival of different CAFC subsets remaining in the femoral bone marrow after treatment with different doses of busulfan (BU) and treosulfan (TR). Error bars represent 95% confidence limits. Biology of Blood and Marrow Transplantation 2004 10, 236-245DOI: (10.1016/j.bbmt.2003.11.004)

Figure 3 Body weight for groups of 5 mice (±1 SEM) given combinations of T cell-depleting mAbs, fludarabine (FL), treosulfan (TR), and thymic irradiation (TI) followed by DLI at 10 weeks after BMT. Biology of Blood and Marrow Transplantation 2004 10, 236-245DOI: (10.1016/j.bbmt.2003.11.004)

Figure 4 Effect of DLI on average blood cell parameters (±1 SEM) in BMT recipients pretreated with anti-CD4/CD8 mAbs and thymic irradiation (TI); anti-CD4/CD8 mAbs, fludarabine (FL), and TI; or anti-CD4/CD8 mAbs, treosulfan (TR), FL, and TI. WBC indicates white blood cell; PLT, platelets; HCT, hematocrit; RBC, red blood cell. Biology of Blood and Marrow Transplantation 2004 10, 236-245DOI: (10.1016/j.bbmt.2003.11.004)

Figure 5 Myeloid and lymphoid allogeneic donor-type chimerism (mean ± SEM for 5 mice per group) after low-dose treosulfan (TR) in various combinations with anti-CD4/CD8 mAbs, fludarabine (FL), and thymic irradiation (TI). Low or undetectable levels of chimerism were also obtained after anti-CD4/CD8 mAbs, FL, and TI or anti-CD4/CD8 mAbs, TR, and TI in 2 other experiments (data not shown). Biology of Blood and Marrow Transplantation 2004 10, 236-245DOI: (10.1016/j.bbmt.2003.11.004)

Figure 6 Effect of DLI on myeloid and lymphoid allogeneic donor-type chimerism (mean ± SEM for 5 mice per group) in BMT recipient mice prepared with anti-CD4/CD8 mAbs and thymic irradiation (TI) with or without the addition of treosulfan (TR) or fludarabine (FL). Biology of Blood and Marrow Transplantation 2004 10, 236-245DOI: (10.1016/j.bbmt.2003.11.004)

Figure 7 Survival of (A) donor-type (B10.A) and (B) third-party (SJL) skin grafts performed at 10 weeks after BMT. The addition of either treosulfan (TR) or fludarabine (FL) to T cell-depleting mAbs and thymic irradiation (TI) led to a significant delay in the donor-type skin rejection rate (P > .005), whereas the addition of both TR and FL resulted in acceptance of skin grafts out to 180 days. Biology of Blood and Marrow Transplantation 2004 10, 236-245DOI: (10.1016/j.bbmt.2003.11.004)