Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation

Karl S. Peggs, Ann Hunter, Rajesh Chopra, Anne Parker, Premini Mahendra, Donald Milligan, Charles Craddock, Ruth Pettengell, Ahmet Dogan, Kirsty J. Thomson, Emma C. Morris, Geoff Hale, Herman Waldmann, Anthony H. Goldstone, David C. Linch, Stephen MacKinnon

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Abstract

Background: In patients with multiply relapsed Hodgkin's lymphoma allogeneic stem-cell transplantation has been limited by prohibitive non-relapse-related mortality rates and by a lack of definitive evidence for a therapeutic graft-versus-tumour effect. Therefore, we aimed to assess the graft-versus-tumour effect of reduced-intensity allogeneic transplantation. Methods: We undertook reduced-intensity transplantation in 49 patients with multiply relapsed Hodgkin's lymphoma, 44 (90%) of whom had progression of disease after previous autologous transplantation (median age 32 years [range 18-51], number of previous treatment courses was five [range 3-8], and time from diagnosis 4.8 years [range 0.6-4.8]). 31 patients had HLA matched donors who were related and 18 had donors who were unrelated. Median follow-up was 967 days (range 102-2232). The primary endpoints were engraftment, toxic effects, non-relapse-related mortality, incidence of graft-versus-host disease (GVHD), and the toxic effects of adjuvant donor-lymphocyte infusion. Findings: All patients engrafted. Eight of 49 (16%) had grade II-IV acute GVHD and seven (14%) had chronic GVHD before donor-lymphocyte infusion. 16 (33%) patients received donor-lymphocyte infusion from 3 months after transplantation for residual disease or progression. Six (38%) of the 16 developed grade II-IV acute GVHD and five developed chronic GVHD. Nine (56%) showed disease responses after infusion (eight complete, one partial). Non-relapse-related mortality was 16.3% at 730 days (7.2% for patients who had related donors vs 34.1% for those with unrelated donors, p=0.0206). Projected 4 year overall and progression-free survival were 55.7% and 39.0%, respectively (62.0% and 41.5% for related donors). Interpretation: These data show the potential for durable responses in patients who have previously had substantial treatment for Hodgkin's lymphoma. The low non-relapse-related mortality suggests the procedure could be undertaken earlier in the course of the disease.

Original languageEnglish (US)
Pages (from-to)1934-1941
Number of pages8
JournalLancet
Volume365
Issue number9475
DOIs
StatePublished - Jun 4 2005
Externally publishedYes

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Homologous Transplantation
Hodgkin Disease
Graft vs Host Disease
Tissue Donors
Transplants
Mortality
Poisons
Lymphocytes
Disease Progression
Transplantation
Unrelated Donors
Autologous Transplantation
Stem Cell Transplantation
Disease-Free Survival
Neoplasms
Therapeutics
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Peggs, K. S., Hunter, A., Chopra, R., Parker, A., Mahendra, P., Milligan, D., ... MacKinnon, S. (2005). Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation. Lancet, 365(9475), 1934-1941. https://doi.org/10.1016/S0140-6736(05)66659-7

Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation. / Peggs, Karl S.; Hunter, Ann; Chopra, Rajesh; Parker, Anne; Mahendra, Premini; Milligan, Donald; Craddock, Charles; Pettengell, Ruth; Dogan, Ahmet; Thomson, Kirsty J.; Morris, Emma C.; Hale, Geoff; Waldmann, Herman; Goldstone, Anthony H.; Linch, David C.; MacKinnon, Stephen.

In: Lancet, Vol. 365, No. 9475, 04.06.2005, p. 1934-1941.

Research output: Contribution to journalArticle

Peggs, KS, Hunter, A, Chopra, R, Parker, A, Mahendra, P, Milligan, D, Craddock, C, Pettengell, R, Dogan, A, Thomson, KJ, Morris, EC, Hale, G, Waldmann, H, Goldstone, AH, Linch, DC & MacKinnon, S 2005, 'Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation', Lancet, vol. 365, no. 9475, pp. 1934-1941. https://doi.org/10.1016/S0140-6736(05)66659-7
Peggs, Karl S. ; Hunter, Ann ; Chopra, Rajesh ; Parker, Anne ; Mahendra, Premini ; Milligan, Donald ; Craddock, Charles ; Pettengell, Ruth ; Dogan, Ahmet ; Thomson, Kirsty J. ; Morris, Emma C. ; Hale, Geoff ; Waldmann, Herman ; Goldstone, Anthony H. ; Linch, David C. ; MacKinnon, Stephen. / Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation. In: Lancet. 2005 ; Vol. 365, No. 9475. pp. 1934-1941.
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abstract = "Background: In patients with multiply relapsed Hodgkin's lymphoma allogeneic stem-cell transplantation has been limited by prohibitive non-relapse-related mortality rates and by a lack of definitive evidence for a therapeutic graft-versus-tumour effect. Therefore, we aimed to assess the graft-versus-tumour effect of reduced-intensity allogeneic transplantation. Methods: We undertook reduced-intensity transplantation in 49 patients with multiply relapsed Hodgkin's lymphoma, 44 (90{\%}) of whom had progression of disease after previous autologous transplantation (median age 32 years [range 18-51], number of previous treatment courses was five [range 3-8], and time from diagnosis 4.8 years [range 0.6-4.8]). 31 patients had HLA matched donors who were related and 18 had donors who were unrelated. Median follow-up was 967 days (range 102-2232). The primary endpoints were engraftment, toxic effects, non-relapse-related mortality, incidence of graft-versus-host disease (GVHD), and the toxic effects of adjuvant donor-lymphocyte infusion. Findings: All patients engrafted. Eight of 49 (16{\%}) had grade II-IV acute GVHD and seven (14{\%}) had chronic GVHD before donor-lymphocyte infusion. 16 (33{\%}) patients received donor-lymphocyte infusion from 3 months after transplantation for residual disease or progression. Six (38{\%}) of the 16 developed grade II-IV acute GVHD and five developed chronic GVHD. Nine (56{\%}) showed disease responses after infusion (eight complete, one partial). Non-relapse-related mortality was 16.3{\%} at 730 days (7.2{\%} for patients who had related donors vs 34.1{\%} for those with unrelated donors, p=0.0206). Projected 4 year overall and progression-free survival were 55.7{\%} and 39.0{\%}, respectively (62.0{\%} and 41.5{\%} for related donors). Interpretation: These data show the potential for durable responses in patients who have previously had substantial treatment for Hodgkin's lymphoma. The low non-relapse-related mortality suggests the procedure could be undertaken earlier in the course of the disease.",
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T1 - Clinical evidence of a graft-versus-Hodgkin's-lymphoma effect after reduced-intensity allogeneic transplantation

AU - Peggs, Karl S.

AU - Hunter, Ann

AU - Chopra, Rajesh

AU - Parker, Anne

AU - Mahendra, Premini

AU - Milligan, Donald

AU - Craddock, Charles

AU - Pettengell, Ruth

AU - Dogan, Ahmet

AU - Thomson, Kirsty J.

AU - Morris, Emma C.

AU - Hale, Geoff

AU - Waldmann, Herman

AU - Goldstone, Anthony H.

AU - Linch, David C.

AU - MacKinnon, Stephen

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Y1 - 2005/6/4

N2 - Background: In patients with multiply relapsed Hodgkin's lymphoma allogeneic stem-cell transplantation has been limited by prohibitive non-relapse-related mortality rates and by a lack of definitive evidence for a therapeutic graft-versus-tumour effect. Therefore, we aimed to assess the graft-versus-tumour effect of reduced-intensity allogeneic transplantation. Methods: We undertook reduced-intensity transplantation in 49 patients with multiply relapsed Hodgkin's lymphoma, 44 (90%) of whom had progression of disease after previous autologous transplantation (median age 32 years [range 18-51], number of previous treatment courses was five [range 3-8], and time from diagnosis 4.8 years [range 0.6-4.8]). 31 patients had HLA matched donors who were related and 18 had donors who were unrelated. Median follow-up was 967 days (range 102-2232). The primary endpoints were engraftment, toxic effects, non-relapse-related mortality, incidence of graft-versus-host disease (GVHD), and the toxic effects of adjuvant donor-lymphocyte infusion. Findings: All patients engrafted. Eight of 49 (16%) had grade II-IV acute GVHD and seven (14%) had chronic GVHD before donor-lymphocyte infusion. 16 (33%) patients received donor-lymphocyte infusion from 3 months after transplantation for residual disease or progression. Six (38%) of the 16 developed grade II-IV acute GVHD and five developed chronic GVHD. Nine (56%) showed disease responses after infusion (eight complete, one partial). Non-relapse-related mortality was 16.3% at 730 days (7.2% for patients who had related donors vs 34.1% for those with unrelated donors, p=0.0206). Projected 4 year overall and progression-free survival were 55.7% and 39.0%, respectively (62.0% and 41.5% for related donors). Interpretation: These data show the potential for durable responses in patients who have previously had substantial treatment for Hodgkin's lymphoma. The low non-relapse-related mortality suggests the procedure could be undertaken earlier in the course of the disease.

AB - Background: In patients with multiply relapsed Hodgkin's lymphoma allogeneic stem-cell transplantation has been limited by prohibitive non-relapse-related mortality rates and by a lack of definitive evidence for a therapeutic graft-versus-tumour effect. Therefore, we aimed to assess the graft-versus-tumour effect of reduced-intensity allogeneic transplantation. Methods: We undertook reduced-intensity transplantation in 49 patients with multiply relapsed Hodgkin's lymphoma, 44 (90%) of whom had progression of disease after previous autologous transplantation (median age 32 years [range 18-51], number of previous treatment courses was five [range 3-8], and time from diagnosis 4.8 years [range 0.6-4.8]). 31 patients had HLA matched donors who were related and 18 had donors who were unrelated. Median follow-up was 967 days (range 102-2232). The primary endpoints were engraftment, toxic effects, non-relapse-related mortality, incidence of graft-versus-host disease (GVHD), and the toxic effects of adjuvant donor-lymphocyte infusion. Findings: All patients engrafted. Eight of 49 (16%) had grade II-IV acute GVHD and seven (14%) had chronic GVHD before donor-lymphocyte infusion. 16 (33%) patients received donor-lymphocyte infusion from 3 months after transplantation for residual disease or progression. Six (38%) of the 16 developed grade II-IV acute GVHD and five developed chronic GVHD. Nine (56%) showed disease responses after infusion (eight complete, one partial). Non-relapse-related mortality was 16.3% at 730 days (7.2% for patients who had related donors vs 34.1% for those with unrelated donors, p=0.0206). Projected 4 year overall and progression-free survival were 55.7% and 39.0%, respectively (62.0% and 41.5% for related donors). Interpretation: These data show the potential for durable responses in patients who have previously had substantial treatment for Hodgkin's lymphoma. The low non-relapse-related mortality suggests the procedure could be undertaken earlier in the course of the disease.

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