Summary:mixed chimerism 5,6 and leukemic relapse, 7-10 especially in patients with chronic myelogenous leukemia (CML).
Based on previous experiences in animals and humans,The role of the T cell subpopulations in aGVHD, graftlow doses of CD8 + lymphocytes infused together with versus-leukemia (GVL) effect and graft failure has been the marrow graft seem to enhance engraftment after studied in experimental animal models and in clinical proallogeneic T cell-depleted marrow transplantation.tocols of selective T cell depletion. [11][12][13][14] It is accepted that From April 1994 to February 1997, 12 patients with both CD4 + and CD8 + lymphocytes are involved in the allochronic myelogenous leukemia in first chronic phase reactive response after BMT, causing aGVHD. 15 Selective receiving a bone marrow transplant (BMT) from an depletion of CD8 + cells from the marrow graft in combi-HLA-identical sibling were included in a pilot study of nation with in vivo cyclosporin A induces a low rate of T cell subset depletion. Total depletion of CD4 + cells of GVHD with about 10% of graft failure after BMT using the marrow graft and partial depletion of CD8 + cells HLA-identical sibling donors. [16][17][18][19] Depletion of both CD4 + was performed by immunomagnetic separation. In and CD8 + cells leads to a low rate of aGVHD even in unorder to improve the engraftment rate, we infused a low related donor BMT, but leukemic relapse still remains a fixed number of CD8 + lymphocytes (0.25 × 10 6 /kg). All problem. 20 the patients were at high risk of developing acute graftIn animal models, it has been postulated that CD8 + cells versus-host disease (GVHD), with a recipient age of Ͼ30 may be important to ensure engraftment after BMT. 21 years, and/or donor sensitized by previous pregnancies Moreover, patients transplanted using a low fixed number or transfusions. All of them received cyclosporin A and of lymphocytes in the graft after physical depletion of T methotrexate post-BMT. No graft failure was observed.cells showed a stable and durable engraftment in the The grade III-IV GVHD rate was 16.6%, and the actumajority of cases, with an effective prevention of arial survival at 3 years is 81.8%. Immunological recovaGVHD. 22,23 ery showed persistent CD8 + HLA-DR + lymphocytosis 8We have developed a program of allogeneic bone marmonths after transplant. Relapses were not observed.row transplantation for patients with CML and with high This experience shows the importance of CD8 + cells to risk of aGVHD, using selective depletion of T cell subsets, ensure correct engraftment, decreasing the GVHD rate.by total immunomagnetic CD4 + depletion and partial CD8 + Keywords: T cell subset depletion; CD8 + lymphocytes; depletion. We infused a low fixed number of CD8 + cells GVHD prevention; graft failure with the graft to attempt an effective prevention of aGVHD, ensuring engraftment and without increasing the rate of leukemic relapses. We have previously reported 24,25 our initial experience Acute graft-versus-host disease (aGVHD) is an import...
CD34+ cells can be highly and effectively isolated from allogeneic and autologous grafts by use of this automated technique, with a high grade of T- and B-cell depletion. These purified CD34+ cell components can engraft normally.
Summary:Twenty-nine B cell follicular lymphoma (FL) patients had their BM (n ؍ 12) or PBPC (n ؍ 17) purged using a panel of monoclonal antibodies and immunomagnetic beads (IMB). The median recovery of nucleated cells (NC) and CD34 ؉ cells was 59.3% (40.5-74) and 56.1% (30.8-82.9) in BM and 77.2% (64.7-88.3) and 73.5% (61.5-98.6) in PBPC (P Ͻ 0.0005). A median of Ͼ1.62 and Ͼ1.02 log of target cell depletion was achieved as judged by flow cytometry analysis in BM and PBPC, respectively. Of 29% of initial harvests that had a bcl2 PCR-amplified signal, 37.5% became PCR negative in the final purged products. Absorbed cells containing IMB-target cell complexes gave bcl2 rearrangement signal in 20% of samples in which the start and final purged components were negative. Twenty-three of 26 patients receiving an autologous purged product are evaluable for engraftment. Median time to reach an ANC Ͼ 0.5 ؋ 10 9 /l and platelet count Ͼ20 ؋ 10 9 /l was 21 (11-43) and 41 days (13-70) for BM (n ؍ 9) and 14 (10-31) and 14 (8-37) for PBPC (n ؍ 14) autografted patients (P ؍ 0.01 and 0.001). One patient did not engraft and was rescued with a back-up BM. These data demonstrate that this indirect immunomagnetic technique is able to achieve a high grade of lymphoma cell depletion in BM and PBPC and that these purged products are capable of rapid engraftment after autologous transplantation.
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