IL-2 does not enhance the conversion to complete donor chimerism following nonmyeloablative hematopoietic cell transplantation in dogs

G. E. Georges; R. Storb; J. Maciej Zaucha; A. G. Taranova; T. Gooley; R. A. Nash

doi:10.1038/sj.bmt.1704046

IL-2 does not enhance the conversion to complete donor chimerism following nonmyeloablative hematopoietic cell transplantation in dogs

G. E. Georges^*, R. Storb, J. Maciej Zaucha, A. G. Taranova, T. Gooley, R. A. Nash

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

A dog model of stable mixed hematopoietic chimerism was established in which leukocyte-antigen-identical littermates receive nonmyeloablative total body irradiation before hematopoietic cell transplantation and postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. Unmodified donor lymphocyte infusion (DLI) into stable mixed chimeras failed to increase donor chimerism, while DLI from donors sensitized to recipient minor-histocompatibility antigens promptly converted all recipients to complete donor chimerism. This established a model for studying approaches to enhance the graft-versus-host (GVH)-effect, a potential surrogate for graft-versus-leukemia activity. We asked if interleukin-2 (IL-2) given after unmodified DLI could result in reliable conversion to complete donor chimerism. IL-2, 4 × 10⁵ IU/kg/day, was administered to six mixed chimeric dogs for 14 days. Four dogs received unmodified DLI with IL-2. At 20-40 weeks after DLI, all dogs remained mixed chimeras. For the two recipients of IL-2 only, mixed chimerism also remained unchanged. These results show that IL-2 given with DLI after nonmyeloablative transplantation in dogs is not effective in reliably converting mixed to complete donor chimerism.

Original language	English (US)
Pages (from-to)	1027-1031
Number of pages	5
Journal	Bone Marrow Transplantation
Volume	31
Issue number	11
DOIs	https://doi.org/10.1038/sj.bmt.1704046
State	Published - Jun 2003

Funding

We are grateful to the technicians of the Shared Canine Resource and the Hematology and Transplantation Biology Laboratories for their technical assistance. We gratefully acknowledge Dr John L Wagner, MD and James Works for DLA typing, and thank Benjamin Weigler, DVM, PhD, and Michelle Spector, DVM, who provided veterinary support. We are very grateful to Bonnie Larson, Helen Crawford, Lori Ausburn, Sue Carbonneau and Karen Carbonneau for their outstanding administrative support. We thank Dr Raymond Tesi and Leila Nawbatt, SangStat, Freemont, CA, for providing Cyclosporine (SangCyas, Cyclosporine Oral solution), Dr Sabine Hadulco, Roche Bioscience, Nutley, NJ, for providing mycophenolate mofetil, and Amgen Inc., Thousand Oaks, CA, for recombinant canine G-CSF. This work was supported in part by Grants DK02753, DK42716, HL63457, CA78902 awarded by the National Institutes of Health, DHHS, Bethesda, MD, USA. RS also received support from the Laura Landro Salomon Endowment Fund and a prize from the Josef Steiner Krebsstiftung, Bern, Switzerland. JMZ is a postdoctoral fellow from the Department of Hematology, University Medical School, Gdańsk, Poland, and is also a recipient of the International Fellowship for Young PhDs, awarded by the Foundation for Polish Science, Warsaw, Poland.

Keywords

Donor lymphocyte infusion
Graft-versus-host effect
Interleukin-2
Nonmyeloablative hematopoietic stem cell transplantation

ASJC Scopus subject areas

Transplantation
Hematology

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10.1038/sj.bmt.1704046

Cite this

@article{66fb83f349ee4886b85bc362b5501073,

title = "IL-2 does not enhance the conversion to complete donor chimerism following nonmyeloablative hematopoietic cell transplantation in dogs",

abstract = "A dog model of stable mixed hematopoietic chimerism was established in which leukocyte-antigen-identical littermates receive nonmyeloablative total body irradiation before hematopoietic cell transplantation and postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. Unmodified donor lymphocyte infusion (DLI) into stable mixed chimeras failed to increase donor chimerism, while DLI from donors sensitized to recipient minor-histocompatibility antigens promptly converted all recipients to complete donor chimerism. This established a model for studying approaches to enhance the graft-versus-host (GVH)-effect, a potential surrogate for graft-versus-leukemia activity. We asked if interleukin-2 (IL-2) given after unmodified DLI could result in reliable conversion to complete donor chimerism. IL-2, 4 × 105 IU/kg/day, was administered to six mixed chimeric dogs for 14 days. Four dogs received unmodified DLI with IL-2. At 20-40 weeks after DLI, all dogs remained mixed chimeras. For the two recipients of IL-2 only, mixed chimerism also remained unchanged. These results show that IL-2 given with DLI after nonmyeloablative transplantation in dogs is not effective in reliably converting mixed to complete donor chimerism.",

keywords = "Donor lymphocyte infusion, Graft-versus-host effect, Interleukin-2, Nonmyeloablative hematopoietic stem cell transplantation",

author = "Georges, {G. E.} and R. Storb and Zaucha, {J. Maciej} and Taranova, {A. G.} and T. Gooley and Nash, {R. A.}",

note = "Funding Information: We are grateful to the technicians of the Shared Canine Resource and the Hematology and Transplantation Biology Laboratories for their technical assistance. We gratefully acknowledge Dr John L Wagner, MD and James Works for DLA typing, and thank Benjamin Weigler, DVM, PhD, and Michelle Spector, DVM, who provided veterinary support. We are very grateful to Bonnie Larson, Helen Crawford, Lori Ausburn, Sue Carbonneau and Karen Carbonneau for their outstanding administrative support. We thank Dr Raymond Tesi and Leila Nawbatt, SangStat, Freemont, CA, for providing Cyclosporine (SangCyas, Cyclosporine Oral solution), Dr Sabine Hadulco, Roche Bioscience, Nutley, NJ, for providing mycophenolate mofetil, and Amgen Inc., Thousand Oaks, CA, for recombinant canine G-CSF. This work was supported in part by Grants DK02753, DK42716, HL63457, CA78902 awarded by the National Institutes of Health, DHHS, Bethesda, MD, USA. RS also received support from the Laura Landro Salomon Endowment Fund and a prize from the Josef Steiner Krebsstiftung, Bern, Switzerland. JMZ is a postdoctoral fellow from the Department of Hematology, University Medical School, Gda{\'n}sk, Poland, and is also a recipient of the International Fellowship for Young PhDs, awarded by the Foundation for Polish Science, Warsaw, Poland.",

year = "2003",

month = jun,

doi = "10.1038/sj.bmt.1704046",

language = "English (US)",

volume = "31",

pages = "1027--1031",

journal = "Bone Marrow Transplantation",

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publisher = "Nature Publishing Group",

number = "11",

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T1 - IL-2 does not enhance the conversion to complete donor chimerism following nonmyeloablative hematopoietic cell transplantation in dogs

AU - Georges, G. E.

AU - Storb, R.

AU - Zaucha, J. Maciej

AU - Taranova, A. G.

AU - Gooley, T.

AU - Nash, R. A.

N1 - Funding Information: We are grateful to the technicians of the Shared Canine Resource and the Hematology and Transplantation Biology Laboratories for their technical assistance. We gratefully acknowledge Dr John L Wagner, MD and James Works for DLA typing, and thank Benjamin Weigler, DVM, PhD, and Michelle Spector, DVM, who provided veterinary support. We are very grateful to Bonnie Larson, Helen Crawford, Lori Ausburn, Sue Carbonneau and Karen Carbonneau for their outstanding administrative support. We thank Dr Raymond Tesi and Leila Nawbatt, SangStat, Freemont, CA, for providing Cyclosporine (SangCyas, Cyclosporine Oral solution), Dr Sabine Hadulco, Roche Bioscience, Nutley, NJ, for providing mycophenolate mofetil, and Amgen Inc., Thousand Oaks, CA, for recombinant canine G-CSF. This work was supported in part by Grants DK02753, DK42716, HL63457, CA78902 awarded by the National Institutes of Health, DHHS, Bethesda, MD, USA. RS also received support from the Laura Landro Salomon Endowment Fund and a prize from the Josef Steiner Krebsstiftung, Bern, Switzerland. JMZ is a postdoctoral fellow from the Department of Hematology, University Medical School, Gdańsk, Poland, and is also a recipient of the International Fellowship for Young PhDs, awarded by the Foundation for Polish Science, Warsaw, Poland.

PY - 2003/6

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N2 - A dog model of stable mixed hematopoietic chimerism was established in which leukocyte-antigen-identical littermates receive nonmyeloablative total body irradiation before hematopoietic cell transplantation and postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. Unmodified donor lymphocyte infusion (DLI) into stable mixed chimeras failed to increase donor chimerism, while DLI from donors sensitized to recipient minor-histocompatibility antigens promptly converted all recipients to complete donor chimerism. This established a model for studying approaches to enhance the graft-versus-host (GVH)-effect, a potential surrogate for graft-versus-leukemia activity. We asked if interleukin-2 (IL-2) given after unmodified DLI could result in reliable conversion to complete donor chimerism. IL-2, 4 × 105 IU/kg/day, was administered to six mixed chimeric dogs for 14 days. Four dogs received unmodified DLI with IL-2. At 20-40 weeks after DLI, all dogs remained mixed chimeras. For the two recipients of IL-2 only, mixed chimerism also remained unchanged. These results show that IL-2 given with DLI after nonmyeloablative transplantation in dogs is not effective in reliably converting mixed to complete donor chimerism.

AB - A dog model of stable mixed hematopoietic chimerism was established in which leukocyte-antigen-identical littermates receive nonmyeloablative total body irradiation before hematopoietic cell transplantation and postgrafting immunosuppression with mycophenolate mofetil and cyclosporine. Unmodified donor lymphocyte infusion (DLI) into stable mixed chimeras failed to increase donor chimerism, while DLI from donors sensitized to recipient minor-histocompatibility antigens promptly converted all recipients to complete donor chimerism. This established a model for studying approaches to enhance the graft-versus-host (GVH)-effect, a potential surrogate for graft-versus-leukemia activity. We asked if interleukin-2 (IL-2) given after unmodified DLI could result in reliable conversion to complete donor chimerism. IL-2, 4 × 105 IU/kg/day, was administered to six mixed chimeric dogs for 14 days. Four dogs received unmodified DLI with IL-2. At 20-40 weeks after DLI, all dogs remained mixed chimeras. For the two recipients of IL-2 only, mixed chimerism also remained unchanged. These results show that IL-2 given with DLI after nonmyeloablative transplantation in dogs is not effective in reliably converting mixed to complete donor chimerism.

KW - Donor lymphocyte infusion

KW - Graft-versus-host effect

KW - Interleukin-2

KW - Nonmyeloablative hematopoietic stem cell transplantation

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ER -

IL-2 does not enhance the conversion to complete donor chimerism following nonmyeloablative hematopoietic cell transplantation in dogs

Abstract

Funding

Keywords

ASJC Scopus subject areas

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