Prevention of transfusion-associated graft-versus-host disease: selection of an adequate dose of gamma radiation

Transfusion ◽  
1993 ◽  
Vol 33 (2) ◽  
pp. 125-127 ◽  
Author(s):  
NR Rosen ◽  
JG Weidner ◽  
HD Boldt ◽  
DS Rosen
Keyword(s):  
Gamma Radiation ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Graft Versus Host ◽  
Adequate Dose ◽  
Selection Of

Prevention of Transfusion-Associated Graft-Versus-Host Disease by Photochemical Treatment

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 3140-3147 ◽  
Author(s):  
Joshua A. Grass ◽  
Tamim Wafa ◽  
Aaron Reames ◽  
David Wages ◽  
Laurence Corash ◽  
...  
Keyword(s):  
T Cells ◽  
Gamma Radiation ◽  
Graft Versus Host Disease ◽  
Clinical Signs ◽  
Peripheral Blood Cell ◽  
Control Group ◽  
Host Disease ◽  
Graft Versus Host

Abstract Photochemical treatment (PCT) with the psoralen S-59 and long wavelength ultraviolet light (UVA) inactivates high titers of contaminating viruses, bacteria, and leukocytes in human platelet concentrates. The present study evaluated the efficacy of PCT to prevent transfusion-associated graft-versus-host disease (TA-GVHD) in vivo using a well-characterized parent to F1 murine transfusion model. Recipient mice in four treatment groups were transfused with 108 splenic leukocytes. (1) Control group mice received syngeneic splenic leukocyte transfusions; (2) GVHD group mice received untreated allogeneic splenic leukocytes; (3) gamma radiation group mice received gamma irradiated (2,500 cGy) allogeneic splenic leukocytes; and (4) PCT group mice received allogeneic splenic leukocytes treated with 150 μmol/L S-59 and 2.1 J/cm2UVA. Multiple biological and clinical parameters were used to monitor the development of TA-GVHD in recipient mice over a 10-week posttransfusion observation period: peripheral blood cell levels, spleen size, engraftment by donor T cells, thymic cellularity, clinical signs of TA-GVHD (weight loss, activity, posture, fur texture, skin integrity), and histologic lesions of liver, spleen, bone marrow, and skin. Mice in the control group remained healthy and free of detectable disease. Mice in the GVHD group developed clinical and histological lesions of TA-GVHD, including pancytopenia, marked splenomegaly, wasting, engraftment with donor derived T cells, and thymic hypoplasia. In contrast, mice transfused with splenic leukocytes treated with (2,500 cGy) gamma radiation or 150 μmol/L S-59 and 2.1 J/cm2 UVA remained healthy and did not develop detectable TA-GVHD. Using an in vitro T-cell proliferation assay, greater than 105.1 murine T cells were inactivated by PCT. Therefore, in addition to inactivating high levels of pathogenic viruses and bacteria in PC, these data indicate that PCT is an effective alternative to gamma irradiation for prevention of TA-GVHD.

Genetics of Graft-Versus-Host Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. SCI-49-SCI-49
Author(s):  
Effie W. Petersdorf
Keyword(s):  
Genetic Variation ◽  
Graft Versus Host Disease ◽  
Hla Typing ◽  
Human Populations ◽  
Sequence Information ◽  
Host Disease ◽  
Graft Versus Host ◽  
New Information ◽  
Unrelated Donors ◽  
Selection Of

Abstract Abstract SCI-49 The HLA barrier remains the primary roadblock to hematopoietic cell transplantation from alternative donors for the treatment of blood disorders. Currently over 18 million unrelated donors are represented by registries worldwide and they serve as a critically important resource for patients in need of a transplant. The basis for the selection of unrelated donors has evolved with advances in HLA typing technology. The demonstration that serologically identical HLA phenotypes have DNA-defined allelic variants that can provoke graft-versus-host reactions has served as the basis for the current criteria for the selection of donors. Although donor HLA matching lowers morbidity and mortality from graft-versus-host disease (GVHD), matching does not guarantee that the patient will not experience life-threatening GVHD and require prolonged immunosuppression after transplantation. Furthermore, the risks of acute and chronic GVHD associated with transplantation from HLA mismatched donors has lead to a reluctance to use mismatched donors for some patients. In 2011, the unmet need is two-fold. First, the vast majority of patients in need of a transplant have no HLA matched unrelated donor. To permit these patients the opportunity for a life-saving transplant, more information on the rules that govern permissible donor-recipient HLA mismatches is needed. Second, information is needed on the extent of non-HLA genetic variation that resides within the major histocompatibility complex (MHC) region and the manner in which such variation contributes to the transplantation barrier. Several research strategies have been applied to identify HLA mismatch combinations that can be used safely, including but not limited to analysis of individual amino acid residues that define the peptide binding repertoire of HLA class I and II alleles and antigens, and computational approaches that relate the sequence to structure of HLA molecules. The availability of a dense map of over 36,000 single nucleotide polymorphisms and complete sequence information for common HLA haplotypes has recently provided new information on the extent of human genetic variation and its organization on haplotypes. These data serve as a rich resource for mapping novel MHC resident variation associated with GVHD risk and transplant outcome. New information is emerging on the diversity of the MHC among transplant patient-donor pairs, the organization of simple and complex genetic variation relative to the classical HLA loci, and the putative regions within the MHC that are amenable to fine mapping. Future investigation of the genetic basis of GVHD will be enhanced with more complete information on MHC region variation in diverse human populations, haplotype content, and robust tools for both querying and analyzing complex variation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Negative selection of T cells causing lethal graft-versus-host disease across minor histocompatibility barriers. Role of the H-2 complex.

1980 ◽  
Vol 151 (5) ◽  
pp. 1114-1124 ◽  
Author(s):  
R Korngold ◽  
J Sprent
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Negative Selection ◽  
Histocompatibility Antigen ◽  
Induction Phase ◽  
Minor Histocompatibility Antigen ◽  
Host Disease ◽  
Graft Versus Host ◽  
Selection Of

With a model in which CBA T cells cause lethal graft-versus-host disease (GVHD) in irradiated B10.BR mice (H-2-compatible mice that express multiple minor histocompatibility antigen [HA] differences), information was sought on whether the induction phase of GVHD to minor HA is H-2 restricted. When unprimed CBA (H-2k) T cells were recirculated from blood to lymph for 1 d through irradiated H-2-compatible B10.BR or B10.K mice, the T cells underwent specific negative selection to the minor HA of the host, i.e, the filtered T cells failed to cause GVHD after transfer to B10.BR mice. With filtration through totally H-2-different B10 (H-2b), B10.D2 (H-2d), or B10.S (H-2s) mice, by contrast, no selection occurred, i.e., the filtered cells were unimpaired in their capacity to kill B10.BR mice. Selection was marked after filtration through H-2-semiallogeneic (B10 X CBA)F1 mice. These data, together with the results of filtering T cells through various H-2 recombinant strains, indicated that selection depended upon the donor and filtration host sharing determinants encoded by both the K- and D-ends of the H-2 complex. Compatibility only in the I region failed to cause demonstrable selection.

Prevention of Transfusion-Associated Graft-Versus-Host Disease by Photochemical Treatment

Blood ◽  
1999 ◽  
Vol 93 (9) ◽  
pp. 3140-3147 ◽  
Author(s):  
Joshua A. Grass ◽  
Tamim Wafa ◽  
Aaron Reames ◽  
David Wages ◽  
Laurence Corash ◽  
...  
Keyword(s):  
T Cells ◽  
Gamma Radiation ◽  
Graft Versus Host Disease ◽  
Clinical Signs ◽  
Peripheral Blood Cell ◽  
Control Group ◽  
Host Disease ◽  
Graft Versus Host

Photochemical treatment (PCT) with the psoralen S-59 and long wavelength ultraviolet light (UVA) inactivates high titers of contaminating viruses, bacteria, and leukocytes in human platelet concentrates. The present study evaluated the efficacy of PCT to prevent transfusion-associated graft-versus-host disease (TA-GVHD) in vivo using a well-characterized parent to F1 murine transfusion model. Recipient mice in four treatment groups were transfused with 108 splenic leukocytes. (1) Control group mice received syngeneic splenic leukocyte transfusions; (2) GVHD group mice received untreated allogeneic splenic leukocytes; (3) gamma radiation group mice received gamma irradiated (2,500 cGy) allogeneic splenic leukocytes; and (4) PCT group mice received allogeneic splenic leukocytes treated with 150 μmol/L S-59 and 2.1 J/cm2UVA. Multiple biological and clinical parameters were used to monitor the development of TA-GVHD in recipient mice over a 10-week posttransfusion observation period: peripheral blood cell levels, spleen size, engraftment by donor T cells, thymic cellularity, clinical signs of TA-GVHD (weight loss, activity, posture, fur texture, skin integrity), and histologic lesions of liver, spleen, bone marrow, and skin. Mice in the control group remained healthy and free of detectable disease. Mice in the GVHD group developed clinical and histological lesions of TA-GVHD, including pancytopenia, marked splenomegaly, wasting, engraftment with donor derived T cells, and thymic hypoplasia. In contrast, mice transfused with splenic leukocytes treated with (2,500 cGy) gamma radiation or 150 μmol/L S-59 and 2.1 J/cm2 UVA remained healthy and did not develop detectable TA-GVHD. Using an in vitro T-cell proliferation assay, greater than 105.1 murine T cells were inactivated by PCT. Therefore, in addition to inactivating high levels of pathogenic viruses and bacteria in PC, these data indicate that PCT is an effective alternative to gamma irradiation for prevention of TA-GVHD.

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