Adoptive immunotherapy in canine mixed chimeras after nonmyeloablative hematopoietic cell transplantation by George E. Georges, Rainer Storb, Jennifer.

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Adoptive immunotherapy in canine mixed chimeras after nonmyeloablative hematopoietic cell transplantation by George E. Georges, Rainer Storb, Jennifer D. Thompson, Cong Yu, Ted Gooley, Benedetto Bruno, and Richard A. Nash Blood Volume 95(10):3262-3269 May 15, 2000 ©2000 by American Society of Hematology

Summary of results from the first unmodified donor lymphocyte infusion (DLI) in 8 stable mixed chimeric recipients.The percentage of donor chimerism in the peripheral blood mononuclear cell (PBMC) fraction is shown from 4 weeks before to 20 weeks after unmo... Summary of results from the first unmodified donor lymphocyte infusion (DLI) in 8 stable mixed chimeric recipients.The percentage of donor chimerism in the peripheral blood mononuclear cell (PBMC) fraction is shown from 4 weeks before to 20 weeks after unmodified DLI. Week 0 is the time of unmodified DLI. George E. Georges et al. Blood 2000;95:3262-3269 ©2000 by American Society of Hematology

Summary of results from minor histocompatibility antigen (mHA)–sensitized DLI in 8 mixed chimeric recipients.The donors were sensitized to recipient mHA after the rejection of recipient skin grafts placed into the donor dog. Summary of results from minor histocompatibility antigen (mHA)–sensitized DLI in 8 mixed chimeric recipients.The donors were sensitized to recipient mHA after the rejection of recipient skin grafts placed into the donor dog. The percentage of donor chimerism in the PBMC fraction is shown over time. Week 0 is the time of mHA-sensitized DLI. The interval between the most recent unmodified DLI and mHA-sensitized DLI was at least 20 weeks, except for dog E367, for which it was 10 weeks. George E. Georges et al. Blood 2000;95:3262-3269 ©2000 by American Society of Hematology

: Representative microsatellite marker studies in recipient dogs at selected times.(A) Dog E390 received 2-Gy total body irradiation (TBI) and dog leukocyte antigen (DLA)–identical marrow from a litter mate and was treated after grafting with mycophenolate ... : Representative microsatellite marker studies in recipient dogs at selected times.(A) Dog E390 received 2-Gy total body irradiation (TBI) and dog leukocyte antigen (DLA)–identical marrow from a litter mate and was treated after grafting with mycophenolate mofetil and cyclosporine for 4 and 5 weeks, respectively. The first unmodified DLI (8.0 × 107 CD3+ cells/kg of body weight) was given 14 weeks after transplantation and the second (10.8 × 107 CD3+ cells/kg) was given 30 weeks after transplantation, without producing a significant change in mixed-chimerism status. In contrast, mHA-sensitized DLI (7.1 × 107 CD3+ cells/kg) given 59 weeks after grafting resulted in rapid conversion to complete donor chimerism, which was sustained beyond 87 weeks after transplantation. (B) Dog E433 received the same transplant regimen, including DLA-identical litter-mate marrow, as dog E390 (above). Unmodified DLI was given twice without producing a change in mixed-chimerism status (data not shown here). Sixty weeks after allografting, mHA-sensitized DLI (8.5 × 107 CD3+/kg) was given, resulting in a rapid increase in donor chimerism to 98%. Host chimerism persisted, and by 105 weeks after allografting, had increased to 15% in both the PBMC and granulocyte fractions. George E. Georges et al. Blood 2000;95:3262-3269 ©2000 by American Society of Hematology

Summary of hematologic data from dog E399, which developed marrow aplasia after mHA-sensitized DLI.(A) Peripheral blood counts recorded from the time of mHA-sensitized DLI. Total white blood cell count (μL), absolute neutrophil count (μL), and platelet coun... Summary of hematologic data from dog E399, which developed marrow aplasia after mHA-sensitized DLI.(A) Peripheral blood counts recorded from the time of mHA-sensitized DLI. Total white blood cell count (μL), absolute neutrophil count (μL), and platelet count (μL) are plotted on the left y axis (log scale). Hematocrit is plotted on the right y axis. Arrows indicate infusion of donor marrow in an attempt to restore hematopoiesis. There was no marked recovery of absolute neutrophil count after marrow infusions. Recombinant granulocyte colony-stimulating factor was administered for the period shown. Dog E399 was humanely killed because of pneumonia 67 days after mHA-sensitized DLI. (B) Representative microsatellite marker studies at selected times. Dog E399 received 4.5-Gy lymph node irradiation, DLA-identical littermate marrow, and postgrafting therapy with mycophenolate mofetil and cyclosporine for 4 weeks and 5 weeks, respectively. Low-level donor chimerism (4%-5%) was unchanged after DLI given 25 weeks after grafting (data not shown). Skin-graft–sensitized mHA-sensitized DLI was given in week 56. After the onset of pancytopenia in week 59, complete donor chimerism was observed in PBMC, granulocyte, and bone marrow fractions. (C) Photomicrograph of biopsy specimen obtained at necropsy from anterior rib marrow of dog E399 showing hypocellular (5%) marrow. Also shown is a rare focus of primarily lymphoid hematopoiesis observed in 2 of 10 fields (arrows). The remaining marrow space contains predominantly red blood cells and few fibroblasts. Biopsy specimens (not shown) from the posterior iliac crest showed complete absence of hematopoiesis. Bar indicates 1 mm. (Stain, hematoxylin & eosin; magnification × 25.)‏ George E. Georges et al. Blood 2000;95:3262-3269 ©2000 by American Society of Hematology