PERIPHERAL BLOOD AND BONE MARROW CELLS AFFECTED BY CAMPATH-1H TREATMENT IN KIDNEY ALLOGRAFT RECIPIENTS.

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PERIPHERAL BLOOD AND BONE MARROW CELLS AFFECTED BY CAMPATH-1H TREATMENT IN KIDNEY ALLOGRAFT RECIPIENTS.
Manuel R. Carreno, MD , James Mathew PhD , Carmen Gomez MT-S , Frank Salman MT-S , Rolando GarciaMorales MD , Joshua Miller MD and Violet Esquenazi PhD . Miami FL, USA, University of Miami, 33136, Surgery-Transplantation ; Miami FL, USA, Miami VA Medical Center, 33136, Research and Miami FL, USA, University of Miami, 33136, Microbiology-Immunology .

In an attempt to induce unresponsiveness to human renal allografts, we have infused donor bone marrow cells (DBMC) perioperatively. This provided a small but significant improvement over conventional treatment and seven years post transplantation microchimerism is still detected. We are evaluating the lymphoablative effects of Campath1-H on peripheral blood (PB) and iliac crest marrow (BM) of 30 kidney recipients (in the absence of DBMC infusions) in whom actuarial graft (and patient) survival thus far is 100% at 1 year. We compared the depletion of discrete mononuclear cell phenotypes sequentially post-transplantation (14, 52, and 222 days). The absolute number of mononuclear cells from PB or BM aspirates per mm³ and the percent remaining post-treatment of the CD3, 19, 56/16, 14, 34 phenotypes and dendritic cells (DC) type I and type II were analyzed by flow cytometry.
Peripherally, (compared to normal values) Campath-1H treatment depleted virtually all lymphocytes, NK cells, DC I and II, and some stem cells in the first few days. A recovery started earlier with stem cells, B cells, monocytes, and NK cells, and later (at 6 months) in T cells. In BM aspirates, Campath-1H strongly reduced the total lymphocyte, CD3⁺, CD19⁺, CD56/16⁺, and CD14⁺ counts. However, virtually normal numbers of stem cells and DC II were found even early post-therapy. At 200 days post-transplant, an increased number of stem cells (double the normal values), B cells and DCs were present in iliac crest marrow.
We speculate that Campath-1H may be a more potent lymphoablative induction agent that may allow more space for engraftment of DBMC tolerogenic lineages.