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Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas.
Biol Blood Marrow Transplant. 2003 Mar; 9(3):162-9.BB

Abstract

Reduced-intensity allogeneic hematopoietic stem cell transplantation (alloHSCT), which typically results in mixed chimerism initially after transplantation, has had limited efficacy in chemotherapy-refractory lymphomas. We hypothesized that the rapid establishment of complete donor chimerism would potentiate a graft-versus-lymphoma effect. Fifteen patients with chemotherapy-refractory lymphoma initially received induction with a conventional chemotherapy regimen (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine [EPOCH-F]) to deplete host T cells and provide disease control prior to alloHSCT. Patients then received conditioning with fludarabine and cyclophosphamide followed by alloHSCT from HLA-matched siblings. Graft-versus-host disease prophylaxis consisted of cyclosporine alone. EPOCH-F resulted in 73% of patients having partial responses or stable disease. EPOCH-F depleted host CD4(+) T cells from a median of 235 cells/microL to 56 cells/microL. Fourteen patients underwent alloHSCT, and all had >95% donor engraftment by day 14 after transplantation. The incidence of Grade II to III acute graft-versus-host disease was 71%. There were two therapy-related deaths. There were 8 partial responses and 3 complete responses (CRs) at day 28. Five additional CRs were observed at day 100 without withdrawal of cyclosporine or donor lymphocyte infusion. The rate of CRs for all 15 patients was 60%. The 1-year progression-free survival rate from time of study entry is 67% with only 1 relapse among 9 CRs. At a median potential follow-up of 28 months, the overall survival rate is 53%. These data demonstrate that a potent and durable graft-versus-lymphoma effect can occur against chemotherapy-refractory lymphomas and suggest that this effect may be associated with rapid, complete donor chimerism after reduced-intensity alloHSCT.

Authors+Show Affiliations

Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. mbishop@mail.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

12652466

Citation

Bishop, Michael R., et al. "Establishment of Early Donor Engraftment After Reduced-intensity Allogeneic Hematopoietic Stem Cell Transplantation to Potentiate the Graft-versus-lymphoma Effect Against Refractory Lymphomas." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 9, no. 3, 2003, pp. 162-9.
Bishop MR, Hou JW, Wilson WH, et al. Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas. Biol Blood Marrow Transplant. 2003;9(3):162-9.
Bishop, M. R., Hou, J. W., Wilson, W. H., Steinberg, S. M., Odom, J., Castro, K., Kasten-Sportes, C., Gea-Banacloche, J., Marchigiani, D., Gress, R., & Fowler, D. H. (2003). Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 9(3), 162-9.
Bishop MR, et al. Establishment of Early Donor Engraftment After Reduced-intensity Allogeneic Hematopoietic Stem Cell Transplantation to Potentiate the Graft-versus-lymphoma Effect Against Refractory Lymphomas. Biol Blood Marrow Transplant. 2003;9(3):162-9. PubMed PMID: 12652466.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Establishment of early donor engraftment after reduced-intensity allogeneic hematopoietic stem cell transplantation to potentiate the graft-versus-lymphoma effect against refractory lymphomas. AU - Bishop,Michael R, AU - Hou,Jeannie Whit-Shan, AU - Wilson,Wyndham H, AU - Steinberg,Seth M, AU - Odom,Jeanne, AU - Castro,Kathleen, AU - Kasten-Sportes,Claude, AU - Gea-Banacloche,Juan, AU - Marchigiani,Donna, AU - Gress,Ronald, AU - Fowler,Daniel H, PY - 2003/3/26/pubmed PY - 2003/12/6/medline PY - 2003/3/26/entrez SP - 162 EP - 9 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 9 IS - 3 N2 - Reduced-intensity allogeneic hematopoietic stem cell transplantation (alloHSCT), which typically results in mixed chimerism initially after transplantation, has had limited efficacy in chemotherapy-refractory lymphomas. We hypothesized that the rapid establishment of complete donor chimerism would potentiate a graft-versus-lymphoma effect. Fifteen patients with chemotherapy-refractory lymphoma initially received induction with a conventional chemotherapy regimen (etoposide, prednisone, vincristine, cyclophosphamide, adriamycin, fludarabine [EPOCH-F]) to deplete host T cells and provide disease control prior to alloHSCT. Patients then received conditioning with fludarabine and cyclophosphamide followed by alloHSCT from HLA-matched siblings. Graft-versus-host disease prophylaxis consisted of cyclosporine alone. EPOCH-F resulted in 73% of patients having partial responses or stable disease. EPOCH-F depleted host CD4(+) T cells from a median of 235 cells/microL to 56 cells/microL. Fourteen patients underwent alloHSCT, and all had >95% donor engraftment by day 14 after transplantation. The incidence of Grade II to III acute graft-versus-host disease was 71%. There were two therapy-related deaths. There were 8 partial responses and 3 complete responses (CRs) at day 28. Five additional CRs were observed at day 100 without withdrawal of cyclosporine or donor lymphocyte infusion. The rate of CRs for all 15 patients was 60%. The 1-year progression-free survival rate from time of study entry is 67% with only 1 relapse among 9 CRs. At a median potential follow-up of 28 months, the overall survival rate is 53%. These data demonstrate that a potent and durable graft-versus-lymphoma effect can occur against chemotherapy-refractory lymphomas and suggest that this effect may be associated with rapid, complete donor chimerism after reduced-intensity alloHSCT. SN - 1083-8791 UR - https://www.unboundmedicine.com/medline/citation/12652466/Establishment_of_early_donor_engraftment_after_reduced_intensity_allogeneic_hematopoietic_stem_cell_transplantation_to_potentiate_the_graft_versus_lymphoma_effect_against_refractory_lymphomas_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083879102000113 DB - PRIME DP - Unbound Medicine ER -