What role is there for antithymocyte globulin in allogeneic nonmyeloablative canine hematopoietic cell transplantation?

Razvan Diaconescu, Marie Térèse Little, Wendy Leisenring, Murad Yunusov, William J. Hogan, Mohamed L. Sorror, Frédéric Baron, Rainer Storb

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

We investigated whether pretransplantation immunosuppression with canine-specific rabbit antithymocyte globulin (ATG), combined with a suboptimal dose of 1 Gy of total body irradiation (TBI), would permit engraftment of canine dog leukocyte antigen-identical marrow. Cumulative ATG doses of 2 to 5 mg/kg produced a T-cell depletion of 1 log in the peripheral blood and 50% in the lymph nodes. Serum levels of ATG peaked on days 4 to 6 after initiation of therapy and became undetectable by day 13 as a result of canine antibody responses to ATG. ATG prolonged allogeneic skin graft survival to 14 days (n = 5), compared with 8 days in control dogs (P = .0003). Five dogs were given marrow transplants after ATG (3.5-5 mg/kg) and 1 Gy of TBI. Posttransplantation immunosuppression consisted of mycophenolate mofetil and cyclosporine. All dogs showed initial engraftment, with maximum donor chimerism levels of 25%. However, only 1 dog achieved sustained engraftment, and 4 rejected their grafts. The duration of engraftment ranged from 8 to ≥36 weeks (median, 11 weeks), and this is comparable to that in 6 historical controls not given ATG (range, 3-12 weeks; median, 10 weeks; P = .20). The total nucleated cell doses in the marrow grafts had the highest correlation coefficient with the duration of engraftment: 0.82 (P = .09). We concluded that administering ATG before an otherwise suboptimal conditioning dose of 1 Gy of TBI failed to secure uniform stable hematopoietic engraftment.

Original languageEnglish (US)
Pages (from-to)335-344
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume11
Issue number5
DOIs
StatePublished - May 1 2005

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Keywords

  • Antithymocyte globulin
  • Dog
  • Hematopoietic cell transplantation
  • Total body irradiation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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