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CD6+ T cell depleted allogeneic bone marrow transplantation from genotypically HLA nonidentical related donors.
Biol Blood Marrow Transplant. 1997 Apr; 3(1):11-7.BB

Abstract

The widespread use of allogeneic bone marrow transplantation (BMT) is limited by the availability of suitable donors. Recent attempts to expand the donor pool by employing HLA matched unrelated marrow have been partially successful. However, severe graft-versus-host disease (GVHD) and graft failure remain obstacles and contribute to the substantial morbidity and mortality associated with matched unrelated BMT. The use of genotypically nonidentical related or unrelated donor marrow could have wider application if problems associated with GVHD could be overcome. Based upon the low incidence of GVHD in recipients of HLA-matched related donor marrow depleted of T cells with T12, an anti-CD6 monoclonal antibody, we applied this approach to 27 adult recipients of HLA mismatched related bone marrow. Ten patients received marrow mismatched at 2 HLA loci, 13 received 1 antigen mismatched marrow, and 4 received phenotypically identical marrow from a non-sibling. Immediately prior to admission, patients were treated with total lymphoid irradiation (750-1050 cGy) to suppress host derived. T lymphocytes capable of mediating graft rejection. The ablative regimen consisted of cyclophosphamide (60 mg/kg x 2 days) followed by total body irradiation (1400 cGy in 7 fractions over 4 days). Patients then received marrow depleted of T cells with T12 (CD6) plus complement. No immune suppressive medications were administered to prevent GVHD. Twenty-four of 27 patients displayed stable hematologic engraftment, achieving an absolute neutrophil count of 0.5 x 10(9)/L at a median of 19 days post-BMT. Degree of HLA disparity did not influence engraftment. Among engrafting patients, grades 2-4 acute GVHD occurred in 40% and grade 3-4 GVHD in 8%. Chronic GVHD developed in 5 patients. Patients mismatched at 2 loci were more likely to develop GVHD than those mismatched at 0-1 loci (logrank, p = .04). Disease relapse has occurred in only 3 patients receiving mismatched marrow. Estimated overall survival for mismatched patients is 56% at 2 years and is independent of HLA disparity. Among the patients transplanted for chronic myelogenous in stable phase or acute leukemia in first remission, estimated event free survival is 69% at 2 years compared to 20% for patients with more advanced disease. Our results suggest that transplantation of mismatched related marrow using modalities designed to reduce GVHD without immune suppressive medication (CD6 depletion) is feasible and should prompt wider investigation into the extended families of patients in the search for potential marrow donors. This approach also merits investigation in recipients of matched unrelated marrow as a potential means of reducing transplant-related toxicity.

Authors+Show Affiliations

Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115, USA.No 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 availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9209736

Citation

Soiffer, R J., et al. "CD6+ T Cell Depleted Allogeneic Bone Marrow Transplantation From Genotypically HLA Nonidentical Related Donors." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 3, no. 1, 1997, pp. 11-7.
Soiffer RJ, Mauch P, Fairclough D, et al. CD6+ T cell depleted allogeneic bone marrow transplantation from genotypically HLA nonidentical related donors. Biol Blood Marrow Transplant. 1997;3(1):11-7.
Soiffer, R. J., Mauch, P., Fairclough, D., Alyea, E., Anderson, K., Fisher, D., Freedman, A., Bartlett-Pandite, L., Robertson, M., Schlossman, R., Gollob, J., Marcus, K., Murray, C., Kuhlman, C., Freeman, A., Nadler, L., & Ritz, J. (1997). CD6+ T cell depleted allogeneic bone marrow transplantation from genotypically HLA nonidentical related donors. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 3(1), 11-7.
Soiffer RJ, et al. CD6+ T Cell Depleted Allogeneic Bone Marrow Transplantation From Genotypically HLA Nonidentical Related Donors. Biol Blood Marrow Transplant. 1997;3(1):11-7. PubMed PMID: 9209736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CD6+ T cell depleted allogeneic bone marrow transplantation from genotypically HLA nonidentical related donors. AU - Soiffer,R J, AU - Mauch,P, AU - Fairclough,D, AU - Alyea,E, AU - Anderson,K, AU - Fisher,D, AU - Freedman,A, AU - Bartlett-Pandite,L, AU - Robertson,M, AU - Schlossman,R, AU - Gollob,J, AU - Marcus,K, AU - Murray,C, AU - Kuhlman,C, AU - Freeman,A, AU - Nadler,L, AU - Ritz,J, PY - 1997/4/1/pubmed PY - 1997/4/1/medline PY - 1997/4/1/entrez SP - 11 EP - 7 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 3 IS - 1 N2 - The widespread use of allogeneic bone marrow transplantation (BMT) is limited by the availability of suitable donors. Recent attempts to expand the donor pool by employing HLA matched unrelated marrow have been partially successful. However, severe graft-versus-host disease (GVHD) and graft failure remain obstacles and contribute to the substantial morbidity and mortality associated with matched unrelated BMT. The use of genotypically nonidentical related or unrelated donor marrow could have wider application if problems associated with GVHD could be overcome. Based upon the low incidence of GVHD in recipients of HLA-matched related donor marrow depleted of T cells with T12, an anti-CD6 monoclonal antibody, we applied this approach to 27 adult recipients of HLA mismatched related bone marrow. Ten patients received marrow mismatched at 2 HLA loci, 13 received 1 antigen mismatched marrow, and 4 received phenotypically identical marrow from a non-sibling. Immediately prior to admission, patients were treated with total lymphoid irradiation (750-1050 cGy) to suppress host derived. T lymphocytes capable of mediating graft rejection. The ablative regimen consisted of cyclophosphamide (60 mg/kg x 2 days) followed by total body irradiation (1400 cGy in 7 fractions over 4 days). Patients then received marrow depleted of T cells with T12 (CD6) plus complement. No immune suppressive medications were administered to prevent GVHD. Twenty-four of 27 patients displayed stable hematologic engraftment, achieving an absolute neutrophil count of 0.5 x 10(9)/L at a median of 19 days post-BMT. Degree of HLA disparity did not influence engraftment. Among engrafting patients, grades 2-4 acute GVHD occurred in 40% and grade 3-4 GVHD in 8%. Chronic GVHD developed in 5 patients. Patients mismatched at 2 loci were more likely to develop GVHD than those mismatched at 0-1 loci (logrank, p = .04). Disease relapse has occurred in only 3 patients receiving mismatched marrow. Estimated overall survival for mismatched patients is 56% at 2 years and is independent of HLA disparity. Among the patients transplanted for chronic myelogenous in stable phase or acute leukemia in first remission, estimated event free survival is 69% at 2 years compared to 20% for patients with more advanced disease. Our results suggest that transplantation of mismatched related marrow using modalities designed to reduce GVHD without immune suppressive medication (CD6 depletion) is feasible and should prompt wider investigation into the extended families of patients in the search for potential marrow donors. This approach also merits investigation in recipients of matched unrelated marrow as a potential means of reducing transplant-related toxicity. SN - 1083-8791 UR - https://www.unboundmedicine.com/medline/citation/9209736/CD6+_T_cell_depleted_allogeneic_bone_marrow_transplantation_from_genotypically_HLA_nonidentical_related_donors_ L2 - http://www.diseaseinfosearch.org/result/7171 DB - PRIME DP - Unbound Medicine ER -