Higher tacrolimus concentrations early after transplant reduce the risk of acute GvHD in reduced-intensity allogeneic stem cell transplantation.

There is significant variability in the serum concentrations of tacrolimus attained early post transplant due to drug interactions and genomic variation. We evaluated whether tacrolimus concentrations early post transplant correlated with incidence of acute GvHD in 120 consecutive patients allografted with a uniform reduced-intensity conditioning regimen. All patients received standard prophylaxis with oral tacrolimus and IV methotrexate. The primary variable of interest was mean weekly tacrolimus concentrations in the initial 4 weeks post transplant. In multivariate analysis, week 1 tacrolimus concentration was an independent predictor of acute grade 2-4 GvHD (hazard ratio (HR), 0.90; 95% confidence interval (CI), 0.84-0.97; P<0.01). This association was driven by a lower risk of acute grade 2-4 GvHD in patients with week 1 tacrolimus concentrations >12 ng/mL (HR, 0.47; 95% CI, 0.25-0.88; P=0.02). Week 1 tacrolimus concentrations were not associated with chronic GvHD, relapse or overall survival. Lower tacrolimus concentrations at weeks 2, 3 and 4 were not associated with a higher incidence of GvHD. In summary, we found that higher tacrolimus concentrations during the first week after allografting with a reduced-intensity conditioning regimen were associated with significantly reduced risk of acute grade 2-4 GvHD without increasing risk of relapse.

Has allogeneic stem cell cryopreservation been given the 'cold shoulder'? An analysis of the pros and cons of using frozen versus fresh stem cell products in allogeneic stem cell transplantation.

Donor stem cells for allogeneic transplant traditionally are collected and transfused 'fresh' into the recipient on the day of transplant; alternatively such cells can be collected in advance and cryopreserved until needed. Most centers favor the former approach based on theoretical concerns that cryopreservation and thawing may worsen clinical outcomes. Limited published data from single institution retrospective studies show no significant impairment of engraftment or reduced day 100 survival for cryopreserved bone marrow recipients. There are no reported outcomes for recipients of cryopreserved peripheral blood allografts. Use of cryopreserved stem cells is associated with a higher incidence of adverse events (transfusion reactions, bacterial graft contamination and collection of grafts which are not utilized). Conversely, use of cryopreserved grafts introduces a greater flexibility into a stressed healthcare system and results in a more streamlined experience for the donor. Some data suggest that transplantation with a cryopreserved product may lower the incidence of acute graft-versus-host disease. We compare the pros and cons of using 'fresh' versus cryopreserved stem cell products for allogeneic transplantation and suggest that the current standard of using 'fresh' products may not be warranted. We also suggest future areas of exploration to better elucidate this issue.