Donor pretreatment with progenipoietin-1 is superior to granulocyte colony-stimulating factor in preventing graft-versus-host disease after allogeneic stem cell transplantation

The granulocyte colony-stimulating factor (G-CSF) and Fit-3 receptor agonist progenipoietin-1 (ProGP-1) has potent effects on dendritic cell (DC) expansion and may be an alternative to G-CSF for the mobilization of stem cells for allogeneic stem cell transplantation (SCT). We studied the ability of stem cell grafts mobilized with this agent to induce graft-versus-host disease (GVHD) to minor and major histocompatibility antigens in the well-described B6 --> B6D2F1 SCT model. ProGP-1, G-CSIF, or control diluent was administered to donor B6 mice. ProGP-1 expanded all cell lineages in the spleen, and unseparated splenocytes from these animals produced large amounts of interleukin 10 (IL-10) and transforming growth factor beta (TGFbeta) whereas the expression of T-cell adhesion molecules was diminished. Transplantation survival was 0%, 50%, and 90% in recipients of control-, G-CSF-, and ProGP-1-treated allogeneic donor splenocytes, respectively (P < .0001). Donor pretreatment with ProGP-1 allowed a 4-fold escalation in T-cell dose over that possible with G-CSF. Donor CD4 T cells from allogeneic SCT recipients of ProGP-1 splenocytes demonstrated an anergic response to host antigen, and cytokine production (interferon gamma [IFNγ], IL-4, and IL-10) was also reduced while CD8 T-cell cytotoxicity to host antigens remained intact. Neither CD11c(hi) DCs nor CD11c(dim)/B220(hi) DCs from ProGP-1-treated animals conferred protection from GVHD when added to control spleen. Conversely, when equal numbers of purified T cells from control-, G-CSF-, or ProGP-1-treated allogeneic donors were added to allogeneic T-cell-depleted control spleen, survival at day 60 was 0%, 15%, and 90%, respectively (P < .0001). The improved survival in recipients of ProGP-1 T cells was associated with reductions in systemic tumor necrosis factor alpha generation and GVHD of the gastrointestinal tract. We conclude that donor pretreatment with ProGP-1 is superior to G-CSIF for the prevention of GVHD after allogeneic SCT, primarily due to incremental affects on T-cell phenotype and function

Characterisation of the signalment, clinical and survival characteristics of 41 cats with mast cell neoplasia

Mast cell tumours (MCTs) are relatively common tumours of cats, and are the second most common cutaneous tumours in cats in the USA. While the primary splenic form of the disease is far less common, it is usually associated with more severe clinical signs. Signalment, clinical and survival characteristics of mast cell neoplasia were characterised in 41 cats. The most common tumour location was cutaneous/ subcutaneous head and trunk. Stage la was the most common tumour stage at first diagnosis (n = 20), followed by stage 4 (both stage 4a and stage 4b; n = 10). Of 22 cats that underwent excisional biopsy, mast cell neoplasia recurred in four cats during the study period. Three of the 41 cats presented with simultaneous cutaneous and either splenic or lymph node tumours. A comparison between cats with only cutaneous tumours (n = 30) and those with tumours involving the spleen or lymph nodes (n = 11) showed longer survival times for the cutaneous-only group (P = 0.031). Twelve of the 41 cats died of mast cell neoplasia during the study period. When a subgroup of cats with only cutaneous tumours (no lymph node or visceral involvement) were divided according to whether there were multiple (five or more) tumours (n = 6) or a single tumour (n = 19), cats with single tumours survived longer than those with multiple tumours (P = 0.001). Solitary cutaneous feline MCTs without spread to the lymph nodes usually manifest as benign disease with a relatively protracted course. However, multiple cutaneous tumours, recurrent tumours and primary splenic disease should receive a guarded prognosis due to the relatively short median survival times associated with these forms of the disease. (C) 2006 ESFM and AAFR Published by Elsevier Ltd. All rights reserved.