Prevention of graft-versus-host disease by selective depletion of CD6-positive T Lymphocytes from Donor Bone Marrow

Robert J. Soiffer, Christine Murray, Peter Mauch, Kenneth C. Anderson, Arnold S. Freedman, Susan N. Rabinowe, Tak Takvorian, Michael Robertson, Neil Spector, Rene Gonin, Kenneth B. Miller, Richard A. Rudders, Andrea Freeman, Kelly Blake, Felice Coral, Lee M. Nodler, Jerome Ritz

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Purpose: Acute and chronic graft-versus-host disease (GVHD) continues to be the major causes of morbidity and mortality after allogeneic bone marrow transplantation (BMT). In this study, we have evaluated the clinical effects of selective in vitro T-cell depletion of donor allogeneic bone marrow by using a single monoclonal antibody ([MoAb] anti-T12, CD6) and rabbit complement. This antibody recognizes mature T cells, but not other cellular elements such as natural-killer (NK) cells, B cells, and myeloid precursors. Patients and Methods: From August 1983 to April 1991, 112 consecutive adult patients with hematologic malignancies underwent BMT with bone marrow from HLA-identical sibling donors. Marrow was harvested and depleted of mature T lymphocytes ex vivo by the use of three rounds of incubation with an anti-T12 antibody and rabbit complement. The preparative regimen consisted of cyclophosphamide and fractionated total body irradiation (TBI) in 108 patients. No patients received prophylactic immune suppression post-BMT. Purgation by anti-T12 was used as the only method for the prevention of GVHD. Results: Twenty patients (18%) developed acute GVHD (grade 2 to 4); only eight patients developed chronic GVHD. The incidence of GVHD did not increase signifi-cantly with age. Only three of 112 patients (2.7%) exhibited acute graft failure. One patient developed late graft failure that was associated with cytomegolovirus (CMV) infection. Within the subset of 50 patients who had not previously undergone unsuccessful conventional therapy (acute leukemia in first remission or chronic myelogenous leukemia [CML] in stable phase), we estimated by the Kaplan-Meier method that the probability of disease-free survival was 50% at 3 years post-BMT, with a median follow-up of 44 months. The treatment-related mortality rate in this group was only 14% and was independent of patient age. Conclusions: We conclude that selective in vitro T-cell depletion with an anti-T12 monoclonal antibody effectively reduces the incidence of both acute and chronic GVHD after allogeneic BMT without compromising engraftment. Moreover, depletion of CD6-positive cells from donor marrow obviates the need to administer immune suppressive medications to the majority of patients. This approach reduces the morbidity and mortality of allogeneic BMT and permits the BMT of older patients.

Original languageEnglish (US)
Pages (from-to)1191-1200
Number of pages10
JournalJournal of Clinical Oncology
Volume10
Issue number7
StatePublished - 1992
Externally publishedYes

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Graft vs Host Disease
Bone Marrow
Tissue Donors
T-Lymphocytes
Bone Marrow Transplantation
Homologous Transplantation
Mortality
Monoclonal Antibodies
Rabbits
Morbidity
Transplants
B-Lymphoid Precursor Cells
Whole-Body Irradiation
Incidence
Hematologic Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Natural Killer Cells
Cyclophosphamide
Disease-Free Survival
Siblings

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Soiffer, R. J., Murray, C., Mauch, P., Anderson, K. C., Freedman, A. S., Rabinowe, S. N., ... Ritz, J. (1992). Prevention of graft-versus-host disease by selective depletion of CD6-positive T Lymphocytes from Donor Bone Marrow. Journal of Clinical Oncology, 10(7), 1191-1200.

Prevention of graft-versus-host disease by selective depletion of CD6-positive T Lymphocytes from Donor Bone Marrow. / Soiffer, Robert J.; Murray, Christine; Mauch, Peter; Anderson, Kenneth C.; Freedman, Arnold S.; Rabinowe, Susan N.; Takvorian, Tak; Robertson, Michael; Spector, Neil; Gonin, Rene; Miller, Kenneth B.; Rudders, Richard A.; Freeman, Andrea; Blake, Kelly; Coral, Felice; Nodler, Lee M.; Ritz, Jerome.

In: Journal of Clinical Oncology, Vol. 10, No. 7, 1992, p. 1191-1200.

Research output: Contribution to journalArticle

Soiffer, RJ, Murray, C, Mauch, P, Anderson, KC, Freedman, AS, Rabinowe, SN, Takvorian, T, Robertson, M, Spector, N, Gonin, R, Miller, KB, Rudders, RA, Freeman, A, Blake, K, Coral, F, Nodler, LM & Ritz, J 1992, 'Prevention of graft-versus-host disease by selective depletion of CD6-positive T Lymphocytes from Donor Bone Marrow', Journal of Clinical Oncology, vol. 10, no. 7, pp. 1191-1200.
Soiffer RJ, Murray C, Mauch P, Anderson KC, Freedman AS, Rabinowe SN et al. Prevention of graft-versus-host disease by selective depletion of CD6-positive T Lymphocytes from Donor Bone Marrow. Journal of Clinical Oncology. 1992;10(7):1191-1200.
Soiffer, Robert J. ; Murray, Christine ; Mauch, Peter ; Anderson, Kenneth C. ; Freedman, Arnold S. ; Rabinowe, Susan N. ; Takvorian, Tak ; Robertson, Michael ; Spector, Neil ; Gonin, Rene ; Miller, Kenneth B. ; Rudders, Richard A. ; Freeman, Andrea ; Blake, Kelly ; Coral, Felice ; Nodler, Lee M. ; Ritz, Jerome. / Prevention of graft-versus-host disease by selective depletion of CD6-positive T Lymphocytes from Donor Bone Marrow. In: Journal of Clinical Oncology. 1992 ; Vol. 10, No. 7. pp. 1191-1200.
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abstract = "Purpose: Acute and chronic graft-versus-host disease (GVHD) continues to be the major causes of morbidity and mortality after allogeneic bone marrow transplantation (BMT). In this study, we have evaluated the clinical effects of selective in vitro T-cell depletion of donor allogeneic bone marrow by using a single monoclonal antibody ([MoAb] anti-T12, CD6) and rabbit complement. This antibody recognizes mature T cells, but not other cellular elements such as natural-killer (NK) cells, B cells, and myeloid precursors. Patients and Methods: From August 1983 to April 1991, 112 consecutive adult patients with hematologic malignancies underwent BMT with bone marrow from HLA-identical sibling donors. Marrow was harvested and depleted of mature T lymphocytes ex vivo by the use of three rounds of incubation with an anti-T12 antibody and rabbit complement. The preparative regimen consisted of cyclophosphamide and fractionated total body irradiation (TBI) in 108 patients. No patients received prophylactic immune suppression post-BMT. Purgation by anti-T12 was used as the only method for the prevention of GVHD. Results: Twenty patients (18{\%}) developed acute GVHD (grade 2 to 4); only eight patients developed chronic GVHD. The incidence of GVHD did not increase signifi-cantly with age. Only three of 112 patients (2.7{\%}) exhibited acute graft failure. One patient developed late graft failure that was associated with cytomegolovirus (CMV) infection. Within the subset of 50 patients who had not previously undergone unsuccessful conventional therapy (acute leukemia in first remission or chronic myelogenous leukemia [CML] in stable phase), we estimated by the Kaplan-Meier method that the probability of disease-free survival was 50{\%} at 3 years post-BMT, with a median follow-up of 44 months. The treatment-related mortality rate in this group was only 14{\%} and was independent of patient age. Conclusions: We conclude that selective in vitro T-cell depletion with an anti-T12 monoclonal antibody effectively reduces the incidence of both acute and chronic GVHD after allogeneic BMT without compromising engraftment. Moreover, depletion of CD6-positive cells from donor marrow obviates the need to administer immune suppressive medications to the majority of patients. This approach reduces the morbidity and mortality of allogeneic BMT and permits the BMT of older patients.",
author = "Soiffer, {Robert J.} and Christine Murray and Peter Mauch and Anderson, {Kenneth C.} and Freedman, {Arnold S.} and Rabinowe, {Susan N.} and Tak Takvorian and Michael Robertson and Neil Spector and Rene Gonin and Miller, {Kenneth B.} and Rudders, {Richard A.} and Andrea Freeman and Kelly Blake and Felice Coral and Nodler, {Lee M.} and Jerome Ritz",
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T1 - Prevention of graft-versus-host disease by selective depletion of CD6-positive T Lymphocytes from Donor Bone Marrow

AU - Soiffer, Robert J.

AU - Murray, Christine

AU - Mauch, Peter

AU - Anderson, Kenneth C.

AU - Freedman, Arnold S.

AU - Rabinowe, Susan N.

AU - Takvorian, Tak

AU - Robertson, Michael

AU - Spector, Neil

AU - Gonin, Rene

AU - Miller, Kenneth B.

AU - Rudders, Richard A.

AU - Freeman, Andrea

AU - Blake, Kelly

AU - Coral, Felice

AU - Nodler, Lee M.

AU - Ritz, Jerome

PY - 1992

Y1 - 1992

N2 - Purpose: Acute and chronic graft-versus-host disease (GVHD) continues to be the major causes of morbidity and mortality after allogeneic bone marrow transplantation (BMT). In this study, we have evaluated the clinical effects of selective in vitro T-cell depletion of donor allogeneic bone marrow by using a single monoclonal antibody ([MoAb] anti-T12, CD6) and rabbit complement. This antibody recognizes mature T cells, but not other cellular elements such as natural-killer (NK) cells, B cells, and myeloid precursors. Patients and Methods: From August 1983 to April 1991, 112 consecutive adult patients with hematologic malignancies underwent BMT with bone marrow from HLA-identical sibling donors. Marrow was harvested and depleted of mature T lymphocytes ex vivo by the use of three rounds of incubation with an anti-T12 antibody and rabbit complement. The preparative regimen consisted of cyclophosphamide and fractionated total body irradiation (TBI) in 108 patients. No patients received prophylactic immune suppression post-BMT. Purgation by anti-T12 was used as the only method for the prevention of GVHD. Results: Twenty patients (18%) developed acute GVHD (grade 2 to 4); only eight patients developed chronic GVHD. The incidence of GVHD did not increase signifi-cantly with age. Only three of 112 patients (2.7%) exhibited acute graft failure. One patient developed late graft failure that was associated with cytomegolovirus (CMV) infection. Within the subset of 50 patients who had not previously undergone unsuccessful conventional therapy (acute leukemia in first remission or chronic myelogenous leukemia [CML] in stable phase), we estimated by the Kaplan-Meier method that the probability of disease-free survival was 50% at 3 years post-BMT, with a median follow-up of 44 months. The treatment-related mortality rate in this group was only 14% and was independent of patient age. Conclusions: We conclude that selective in vitro T-cell depletion with an anti-T12 monoclonal antibody effectively reduces the incidence of both acute and chronic GVHD after allogeneic BMT without compromising engraftment. Moreover, depletion of CD6-positive cells from donor marrow obviates the need to administer immune suppressive medications to the majority of patients. This approach reduces the morbidity and mortality of allogeneic BMT and permits the BMT of older patients.

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