Abstract

Dexamethasone and other steroids are potent inhibitor of allo reactive T cells and are widely used as therapy for GVHD and other immune mediated clinical syndromes and we hypothesized use of a short course of steroids given to sibling donors could potentially decrease the number of allo reactive T cells in the graft, and thereby decrease incidence of graft versus host disease. Here we report the out come of a total of 118 patients who underwent allogeneic matched sibling transplantation between 09/1998 to 05/2006 at the UAB BMT program. Patient characteristics are given in table. Most common conditioning regimen was IV Busulfan (AUC targeted to 1000) and Fludarabine. GVHD prophylaxis was cyclosporine and long course methotrexate in the majority of patients. 74 patients had received ATG. Median patient age is 47.8 (ranges 18–68.2) and median donor age is 44.8 (range 13.3–70.3). Donors were mobilized with rhg-CSF for 4 days and dexamethasone 10mg/m2/day for 3 days followed by stem cell collection. 31 out of the 118 patients developed grade 2–4 aGVHD (26.5%) and 42 patients (35.6%) developed extensive cGVHD. The over all TRM was 29.6%. aGVHD caused an increase in TRM as well as overall mortality; median survival of those with aGVHD was 115 days compared to 481 days among those who did not (PWilcoxon =0.0003). On the other hand, cGVHD was associated with an increased median survival; median survival of those with extensive cGVHD was 589 days compared to 115 days in those without (PWilcoxon <0.0001) The relapse free time is also significantly associated with cGVHD, with less relapses in patients who developed extensive cGVHD. (P Wilcoxon = 0.0328) Development of extensive chronic GVHD was not dependent up on graft content in this population. With the use of dexamethasone during mobilization, the mean number of CD34+ yield was significantly higher (mean 8.9×106; median 7.8× 106 range = 1.8×106–3.97 107) compared to mean 4.9×106 cells/kg, median 3.0× 106 (range = 2.3×105–7.6×107) from a historic cohort of 46 patients at UAB whose donors did not receive dexamethasone (P< 0.0001). On the other hand, the mean number of CD3+ content in the dexamethasone arm was less (mean 3.3× 10 7 cells/kg, range: 8.2×10 6–8.9×10 9) than that in the non-dexamethasone arm (mean of 4.4 × 10 8 cells/kg, range: 6.210 7–4.610 9; P= <0.0001). No adverse event other than that is expected from high dose rhg-CSF was reported by the donors who received the short duration of dexamethasone. We have shown here that dexamethasone can be safely used in donors with a resultant depletion in the number of CD3+ cells without compromising engraftment or increase in relapse. The overall incidence of grade 2–4 acute GVHD (26.5%) among our patients who received dexamethasone + rhg-CSF mobilized PBSC is less than that are reported in literature.

Patient Characteristics

SEXM=60%F=40%
RACE W=84% B=14% O=2%   
ASBMT RISK HR=41% IR=22% LR=28% OTHER=9%  
DISEASE AML+ALL=34% NHL=23% Myeloma=7% MDS=6% OTHER=30% 
CMV POSITIVE=70% NEGATIVE=30%    
SEXM=60%F=40%
RACE W=84% B=14% O=2%   
ASBMT RISK HR=41% IR=22% LR=28% OTHER=9%  
DISEASE AML+ALL=34% NHL=23% Myeloma=7% MDS=6% OTHER=30% 
CMV POSITIVE=70% NEGATIVE=30%    

Author notes

Disclosure:Membership Information: Speakers Bureau, MGI Pharma, Advisory Committee, Pharmion.