LOW INCIDENCE OF ACUTE GRAFT-VERSUS-HOST DISEASE, USING UNRELATED HLA-A-, HLA-B-, AND HLA-DR-COMPATIBLE DONORS AND CONDITIONING, INCLUDING ANTI-T-CELL ANTIBODIES1

In a series of patients transplanted with HLA-matched allogeneic bone marrow grafts (alloBMT), we previously showed that a few T-cell receptor (TCR) V alpha and V beta gene segment transcripts were overexpressed in skin compared with blood at the time of acute graft- versus-host disease (aGVHD). Here, in one selected patient with overexpressed V beta 16 and V alpha 11 transcripts in skin, we analyzed the junctional variability of these transcripts in donor blood, patient blood, and skin collected at aGVHD onset. A unique junctional region sequence accounted for 81% of in frame V beta 16 transcripts (13 of 16) in skin and 59% (13 of 22) in patient blood. Similarly, two recurrent junctional region sequences were found in skin V alpha 11 transcripts, one accounting for 66% (21 of 32) and the other for 16% (5 of 32). These recurrences were also found in patient blood (36% and 15% of V alpha 11 transcripts, respectively). To extend our analysis, a polymerase chain reaction (PCR)-based method was used to precisely determine TCR beta transcript length in run-off reactions using uncloned bulk cDNA samples. All V beta-C beta PCR products analyzed in donor blood, as well as the majority of those analyzed in patient blood, included transcripts with highly diverse junctional region sizes. As expected from the sequence data, most V beta 16-C beta PCR products in skin and patient blood were of the same size (ie, same junctional region). In addition, V beta 3, V beta 5, and V beta 17 transcripts in skin were shown to display highly restricted size variability. The clonality of the V beta 16-C beta and V beta 17-C beta transcripts was further supported by the results of run-off reactions using 13 J beta specific primers. We have identified several recurrent TCR transcripts in skin, some of them also present in patient blood. These data support the view that several T-cell subpopulations are clonally expanded in vivo at the time of aGVHD onset in this case of related HLA-matched alloBMT.

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Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft- versus -host disease: low incidence of lower gastrointestinal tract disease

Haematologica ◽

10.3324/haematol.2017.183434 ◽

2018 ◽

Vol 103 (4) ◽

pp. 717-727 ◽

Cited By ~ 11

Author(s):

William R. Drobyski ◽

Aniko Szabo ◽

Fenlu Zhu ◽

Carolyn Keever-Taylor ◽

Kyle M. Hebert ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Graft Versus Host Disease ◽

Lower Gastrointestinal Tract ◽

Host Disease ◽

Graft Versus Host ◽

Low Incidence ◽

Tract Disease ◽

Acute Graft

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Tryptophan metabolite analog, N-(3,4-dimethoxycinnamonyl) anthranilic acid, ameliorates acute graft-versus-host disease through regulating T cell proliferation and polarization

International Immunopharmacology ◽

10.1016/j.intimp.2013.08.004 ◽

2013 ◽

Vol 17 (3) ◽

pp. 601-607 ◽

Cited By ~ 5

Author(s):

Jinhuan Xu ◽

Jia Wei ◽

Min Huang ◽

Xianmin Zhu ◽

Jun Guan ◽

...

Keyword(s):

Cell Proliferation ◽

T Cell ◽

Graft Versus Host Disease ◽

Anthranilic Acid ◽

T Cell Proliferation ◽

Host Disease ◽

Graft Versus Host ◽

Tryptophan Metabolite ◽

Metabolite Analog ◽

Acute Graft

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In vivo T-cell clonal amplification at time of acute graft-versus-host disease

Blood ◽

10.1182/blood.v84.8.2815.2815 ◽

1994 ◽

Vol 84 (8) ◽

pp. 2815-2820 ◽

Cited By ~ 57

Author(s):

PY Dietrich ◽

A Caignard ◽

A Lim ◽

V Chung ◽

JL Pico ◽

...

Keyword(s):

T Cell ◽

Graft Versus Host Disease ◽

Donor Blood ◽

Host Disease ◽

Graft Versus Host ◽

Junctional Region ◽

Run Off ◽

Pcr Products ◽

Acute Graft

Abstract In a series of patients transplanted with HLA-matched allogeneic bone marrow grafts (alloBMT), we previously showed that a few T-cell receptor (TCR) V alpha and V beta gene segment transcripts were overexpressed in skin compared with blood at the time of acute graft- versus-host disease (aGVHD). Here, in one selected patient with overexpressed V beta 16 and V alpha 11 transcripts in skin, we analyzed the junctional variability of these transcripts in donor blood, patient blood, and skin collected at aGVHD onset. A unique junctional region sequence accounted for 81% of in frame V beta 16 transcripts (13 of 16) in skin and 59% (13 of 22) in patient blood. Similarly, two recurrent junctional region sequences were found in skin V alpha 11 transcripts, one accounting for 66% (21 of 32) and the other for 16% (5 of 32). These recurrences were also found in patient blood (36% and 15% of V alpha 11 transcripts, respectively). To extend our analysis, a polymerase chain reaction (PCR)-based method was used to precisely determine TCR beta transcript length in run-off reactions using uncloned bulk cDNA samples. All V beta-C beta PCR products analyzed in donor blood, as well as the majority of those analyzed in patient blood, included transcripts with highly diverse junctional region sizes. As expected from the sequence data, most V beta 16-C beta PCR products in skin and patient blood were of the same size (ie, same junctional region). In addition, V beta 3, V beta 5, and V beta 17 transcripts in skin were shown to display highly restricted size variability. The clonality of the V beta 16-C beta and V beta 17-C beta transcripts was further supported by the results of run-off reactions using 13 J beta specific primers. We have identified several recurrent TCR transcripts in skin, some of them also present in patient blood. These data support the view that several T-cell subpopulations are clonally expanded in vivo at the time of aGVHD onset in this case of related HLA-matched alloBMT.

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Skin-Selective CD8 T-Cell Depletion by Photoimmunotherapy Inhibits Human Cutaneous Acute Graft-Versus-Host Disease

Journal of Investigative Dermatology ◽

10.1016/j.jid.2019.12.009 ◽

2020 ◽

Vol 140 (7) ◽

pp. 1455-1459.e6

Author(s):

Lukas Freund ◽

Stephanie Oehrl ◽

Galina Gräbe ◽

Patrick Gholam ◽

Thomas Plum ◽

...

Keyword(s):

T Cell ◽

Graft Versus Host Disease ◽

Cd8 T Cell ◽

Cell Depletion ◽

T Cell Depletion ◽

Host Disease ◽

Graft Versus Host ◽

Acute Graft

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Interleukin-1 blockade does not prevent acute graft-versus-host disease: results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation

Blood ◽

10.1182/blood-2002-03-0985 ◽

2002 ◽

Vol 100 (10) ◽

pp. 3479-3482 ◽

Cited By ~ 117

Author(s):

Joseph H. Antin ◽

Daniel Weisdorf ◽

Donna Neuberg ◽

Roberta Nicklow ◽

Shawn Clouthier ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Receptor Antagonist ◽

Graft Versus Host Disease ◽

Interleukin 1 ◽

Double Blind ◽

Host Disease ◽

Double Blind Placebo ◽

Graft Versus Host ◽

Acute Graft

Acute graft-versus-host disease (GVHD) is thought to derive from direct T-cell injury of target tissues through perforin/granzyme, Fas/FasL interactions, and the effects of inflammatory cytokines. Animal models and some clinical trials support the notion that inhibition of inflammatory mediators such as interleukin-1 (IL-1), tumor necrosis factor α, and interferon γ may ameliorate or prevent GVHD. We hypothesized that blockade of IL-1 during the period of initial T-cell activation would reduce the risk of severe GVHD. We tested this hypothesis in a double-blind, placebo-controlled randomized trial of recombinant human IL-1 receptor antagonist (IL-1Ra) in 186 patients undergoing allogeneic stem cell transplantation. Randomization was stratified by degree of histocompatibility and stem cell source. All patients were conditioned with cyclophosphamide and total body irradiation. GVHD prevention consisted of cyclosporine and methotrexate in all patients. Recombinant human IL-1Ra or saline placebo was given from day −4 to day +10. Randomization was stratified according to GVHD risk. The 2 groups were well-matched for pretreatment characteristics. Moderate to severe GVHD (grades B-D) developed in 57 (61%) of 94 patients receiving IL-1Ra and in 51 (59%) of 86 patients on placebo (P = .88). There was no difference in hematologic recovery, transplantation-related toxicity, event-free survival, or overall survival. We conclude that blockade of IL-1 using IL-1Ra during conditioning and 10 days immediately after transplantation is not sufficient to reduce GVHD or toxicity or to improve survival.

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