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Biotech / Medical : Biotransplant(BTRN) -- Ignore unavailable to you. Want to Upgrade?

To: Arthur Radley who wrote (1105)	11/12/2001 9:26:59 PM
From: Arthur Radley	Read Replies (1) \| Respond to of 1475

part 4 by: soldier30 11/12/01 08:53 pm Msg: 1295 of 1302 Abstract number 3554 A Randomized Trial of CD8+ T Cell Depletion To Prevent Graft-Vs-Host Disease (GVHD) Associated with Donor Lymphocyte Infusions. Robert J. Soiffer, Edwin P. Alyea, Christine Canning, Ephraim Hochberg, David Zahrieh, Bijal Parikh, Iain Webb, Joseph Antin, Jerome RitzAdult Oncology, Dana Farber Cancer Institute, Boston, MA, USA Adoptive immunotherapy with donor lymphocyte infusions (DLI) has been employed for the treatment and prevention of disease recurrence following allogeneic bone marrow transplantation (BMT). Unfortunately, DLI is associated with the development of GVHD which limits its therapeutic utility. Single arm trials have suggested that CD8+ depletion of donor lymphocytes may reduce the incidence of GVHD without compromising efficacy. To test the impact of CD8 depletion on GVHD, we initiated a randomized trial comparing outcome of patients (pts) receiving unselected donor lymphocytes to pts receiving DLI depleted of CD8+ cells. DLI was administered to high risk pts to prevent disease relapse 5-6 months after they had undergone a T cell depleted allogeneic BMT. Between 6/98 and 12/99, 18 pts were enrolled. The median age was 46 years (range, 24-66). There were 6 males/12 females. Diseases included AML (9), MDS (2), ALL (2), myelofibrosis (2), CLL (2), and NHL(1). CD8 depletion was performed with monoclonal antibody and rabbit complement. Donor lymphocytes were obtained from the original donor in 1 or 2 leukapheresis sessions and were infused fresh without cryopreservation. Infusions were adjusted so that all pts received 1.0 x 107 CD4+ cells/kg. Pts randomized to CD8 depletion received a median of 0.7 x 105 CD8+ cells/kg compared to 32.0 x 105 CD8+ cells/kg in the unmanipulated cohort. The median numbers of CD3+ cells/kg infused were 1.08 and 1.56 x 107, respectively, in the CD8 depleted and unmanipulated groups. The median follow-up of both groups is 19 months post-DLI (range 8-37 months). Six of 9 (67%) of pts receiving unselected DLI developed acute GVHD compared with 0 of 9 (0%) recipients of CD8 depleted DLI (p = 0.009). In the unselected group, there have been 2 deaths in remission (one directly from GVHD) and three relapses. In the CD8 depleted cohort, there have been no toxic deaths and only one relapse. Estimated two-year relapse free survival post-BMT in the CD8 depleted group is 86% compared with 52% in the pts who received unselected DLI (p = 0.14). Immunophenotypic analysis of peripheral blood samples up to 18 months post-DLI revealed no differences between the two groups. Measures of thymic function and T cell reconstitution by T cell receptor excision circle (TREC) analysis demonstrated similar patterns of recovery in both the CD8 depleted and unselected cohorts. Immediately before DLI, pts in both groups had an average of 60% donor cells by hematopoietic chimerism analysis with restriction fragment length polymorphisms (RFLP). By 12 months after DLI, an average of 98% of hematopoietic cells were of donor origin in both groups. Our results indicate that CD8 depletion reduces the incidence of GVHD associated with DLI without compromising anti-tumor activity, conversion to donor hematopoiesis, or immunologic recovery.