CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation

S. Giralt, J. Hester, Y. Huh, C. Hirsch-Ginsberg, G. Rondon, D. Seong, M. Lee, J. Gajewski, K. Van Besien, I. Khouri, R. Mehra, D. Przepiorka, M. Korbling, M. Talpaz, H. Kantarjian, H. Fischer, A. Deisseroth, R. Champlin

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Abstract

Donor lymphocyte infusions can reinduce complete remission in the majority of patients with chronic myelogenous leukemia (CML) who relapse into chronic phase after allogeneic bone marrow transplantation (BMT). Such infusions are associated with a high incidence of graft-versus-host disease (GVHD) and marrow aplasia. BMT using selective depletion of CD8+ lymphocytes from donor cells reduces the incidence of GVHD without an increase in leukemia relapse. We hypothesized that infusion of CD8-depleted donor peripheral blood lymphocytes could also reinduce complete remissions with a lesser potential to produce symptomatic GVHD in patients with CML who relapsed after allogeneic BMT. Ten patients with Ph(+) CML who relapsed a median of 353 days after BMT (range, 82 to 1,096 days) received donor lymphocyte infusions depleted of CD8+ cells. Nine patients received a single infusion and 1 received two infusions. Four patients were treated while in chronic phase with clonal evolution, 2 during accelerated phase, 3 during blast crisis, and 1 in a cytogenetic relapse. A mean of 0.9 ± 0.3 x 108 mononuclear cells/kg were infused, containing 0.6 ± 0.4 x 106 CD3+CD8+ cells/kg. Six patients achieved hematologic and cytogenetic remission at 4, 8, 11, 15, 39, and 54 weeks after lymphocyte infusion. Two patients developed ≥grade II acute GVHD, and I patient developed mild chronic GVHD. We conclude that donor lymphocyte infusions depleted of CD8+ cells can induce remissions with a low rate of severe acute GVHD in patients with CML who relapse after allogeneic BMT, supporting the hypothesis that CD8+ lymphocytes are important effectors of GVHD, but may not be essential for the graft-versus-leukemia effect against this disease. Further controlled studies are required to confirm these preliminary observations.

Original languageEnglish (US)
Pages (from-to)4337-4343
Number of pages7
JournalBlood
Volume86
Issue number11
StatePublished - 1995
Externally publishedYes

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Lymphocytes
Homologous Transplantation
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bone Marrow Transplantation
Grafts
Graft vs Host Disease
Bone
Tissue Donors
Recurrence
Therapeutics
Cytogenetics
Leukemia
Clonal Evolution
Lymphocyte Depletion
Blast Crisis
Incidence
Blood Donors
Blood
Bone Marrow
Transplants

ASJC Scopus subject areas

  • Hematology

Cite this

Giralt, S., Hester, J., Huh, Y., Hirsch-Ginsberg, C., Rondon, G., Seong, D., ... Champlin, R. (1995). CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. Blood, 86(11), 4337-4343.

CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. / Giralt, S.; Hester, J.; Huh, Y.; Hirsch-Ginsberg, C.; Rondon, G.; Seong, D.; Lee, M.; Gajewski, J.; Van Besien, K.; Khouri, I.; Mehra, R.; Przepiorka, D.; Korbling, M.; Talpaz, M.; Kantarjian, H.; Fischer, H.; Deisseroth, A.; Champlin, R.

In: Blood, Vol. 86, No. 11, 1995, p. 4337-4343.

Research output: Contribution to journalArticle

Giralt, S, Hester, J, Huh, Y, Hirsch-Ginsberg, C, Rondon, G, Seong, D, Lee, M, Gajewski, J, Van Besien, K, Khouri, I, Mehra, R, Przepiorka, D, Korbling, M, Talpaz, M, Kantarjian, H, Fischer, H, Deisseroth, A & Champlin, R 1995, 'CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation', Blood, vol. 86, no. 11, pp. 4337-4343.
Giralt S, Hester J, Huh Y, Hirsch-Ginsberg C, Rondon G, Seong D et al. CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. Blood. 1995;86(11):4337-4343.
Giralt, S. ; Hester, J. ; Huh, Y. ; Hirsch-Ginsberg, C. ; Rondon, G. ; Seong, D. ; Lee, M. ; Gajewski, J. ; Van Besien, K. ; Khouri, I. ; Mehra, R. ; Przepiorka, D. ; Korbling, M. ; Talpaz, M. ; Kantarjian, H. ; Fischer, H. ; Deisseroth, A. ; Champlin, R. / CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. In: Blood. 1995 ; Vol. 86, No. 11. pp. 4337-4343.
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abstract = "Donor lymphocyte infusions can reinduce complete remission in the majority of patients with chronic myelogenous leukemia (CML) who relapse into chronic phase after allogeneic bone marrow transplantation (BMT). Such infusions are associated with a high incidence of graft-versus-host disease (GVHD) and marrow aplasia. BMT using selective depletion of CD8+ lymphocytes from donor cells reduces the incidence of GVHD without an increase in leukemia relapse. We hypothesized that infusion of CD8-depleted donor peripheral blood lymphocytes could also reinduce complete remissions with a lesser potential to produce symptomatic GVHD in patients with CML who relapsed after allogeneic BMT. Ten patients with Ph(+) CML who relapsed a median of 353 days after BMT (range, 82 to 1,096 days) received donor lymphocyte infusions depleted of CD8+ cells. Nine patients received a single infusion and 1 received two infusions. Four patients were treated while in chronic phase with clonal evolution, 2 during accelerated phase, 3 during blast crisis, and 1 in a cytogenetic relapse. A mean of 0.9 ± 0.3 x 108 mononuclear cells/kg were infused, containing 0.6 ± 0.4 x 106 CD3+CD8+ cells/kg. Six patients achieved hematologic and cytogenetic remission at 4, 8, 11, 15, 39, and 54 weeks after lymphocyte infusion. Two patients developed ≥grade II acute GVHD, and I patient developed mild chronic GVHD. We conclude that donor lymphocyte infusions depleted of CD8+ cells can induce remissions with a low rate of severe acute GVHD in patients with CML who relapse after allogeneic BMT, supporting the hypothesis that CD8+ lymphocytes are important effectors of GVHD, but may not be essential for the graft-versus-leukemia effect against this disease. Further controlled studies are required to confirm these preliminary observations.",
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AU - Giralt, S.

AU - Hester, J.

AU - Huh, Y.

AU - Hirsch-Ginsberg, C.

AU - Rondon, G.

AU - Seong, D.

AU - Lee, M.

AU - Gajewski, J.

AU - Van Besien, K.

AU - Khouri, I.

AU - Mehra, R.

AU - Przepiorka, D.

AU - Korbling, M.

AU - Talpaz, M.

AU - Kantarjian, H.

AU - Fischer, H.

AU - Deisseroth, A.

AU - Champlin, R.

PY - 1995

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N2 - Donor lymphocyte infusions can reinduce complete remission in the majority of patients with chronic myelogenous leukemia (CML) who relapse into chronic phase after allogeneic bone marrow transplantation (BMT). Such infusions are associated with a high incidence of graft-versus-host disease (GVHD) and marrow aplasia. BMT using selective depletion of CD8+ lymphocytes from donor cells reduces the incidence of GVHD without an increase in leukemia relapse. We hypothesized that infusion of CD8-depleted donor peripheral blood lymphocytes could also reinduce complete remissions with a lesser potential to produce symptomatic GVHD in patients with CML who relapsed after allogeneic BMT. Ten patients with Ph(+) CML who relapsed a median of 353 days after BMT (range, 82 to 1,096 days) received donor lymphocyte infusions depleted of CD8+ cells. Nine patients received a single infusion and 1 received two infusions. Four patients were treated while in chronic phase with clonal evolution, 2 during accelerated phase, 3 during blast crisis, and 1 in a cytogenetic relapse. A mean of 0.9 ± 0.3 x 108 mononuclear cells/kg were infused, containing 0.6 ± 0.4 x 106 CD3+CD8+ cells/kg. Six patients achieved hematologic and cytogenetic remission at 4, 8, 11, 15, 39, and 54 weeks after lymphocyte infusion. Two patients developed ≥grade II acute GVHD, and I patient developed mild chronic GVHD. We conclude that donor lymphocyte infusions depleted of CD8+ cells can induce remissions with a low rate of severe acute GVHD in patients with CML who relapse after allogeneic BMT, supporting the hypothesis that CD8+ lymphocytes are important effectors of GVHD, but may not be essential for the graft-versus-leukemia effect against this disease. Further controlled studies are required to confirm these preliminary observations.

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