ABSTRACT
New strategies that modify the coagulation/inflammatory cascades may be applicable to solid organ transplant (SOT) recipients in the treatment of complications. However, data on kinetics of post-SOT cascades are needed before considering these strategies. Prospectively collected pre-transplant serum measurements of inflammatory (high-sensitive C-reactive protein, HS-CRP) and coagulation (d-Dimer, DD; protein C, PC) markers were compared to post-operative (day 1-90) values in deceased-donor liver (DDLT) and renal (DDRT) transplant recipients, living-related renal recipients (LRT) and donors (LRD). A total of 85 SOT were enrolled: 25 DDLT, 32 DDRT/LRT, 28 LRD. HS-CRP increased in all groups, mainly immediate post-SOT and in LRDs. DD had a similar pattern mainly in LRT and LRD. PC increased significantly over time in the DDLT group ( p < 0.01). Compared to those with no complications (infection, rejection or thrombosis), day 30 HS-CRP (p = 0.04) and DD (p = 0.06) were elevated in the DDRT/LRT group with complications; PC was decreased at day 7 (p = 0.04) and day 30 (p = 0.009) in DDLT and DDRT/LRT groups with complications, respectively. In conclusion, activation of the inflammatory/coagulation cascades occurs after SOT and is least pronounced in DDLT. This activation diminishes over time unless transplant complications occur. Our results support further research in approaches to altering these cascades in SOT recipients.
Subject(s)
Biomarkers/blood , Blood Coagulation/physiology , Inflammation/blood , Kidney Transplantation , Liver Transplantation , Postoperative Complications/blood , Adult , C-Reactive Protein/metabolism , Female , Fibrin Fibrinogen Degradation Products/metabolism , Follow-Up Studies , Graft Rejection/blood , Humans , Male , Middle Aged , Pilot Projects , Postoperative Period , Prognosis , Prospective Studies , Protein C/metabolismABSTRACT
Consistent data for using CMV quantitative PCR (QnPCR) on initial presentation to predict outcomes after solid organ transplantation (SOT) are lacking. Recipients with measurable CMV QnPCR and either CMV-V (asymptomatic viremia) or CMV-D (symptomatic CMV infection) were analyzed over 24 months. Risk factors and outcomes were evaluated in relation to initial QnPCR by regression analysis and time-to-event curves. Twenty-eight recipients were identified: five CMV-V, 23 CMV-D. Patients with CMV-D had a higher median initial QnPCR (230 000 copies/mL) compared with CMV-V (2500 copies/mL; p < 0.05). No patients with CMV-V had an initial QnPCR > 10 000 copies/mL compared with 83% of the CMV-D (p = 0.004). The initial QnPCR was higher (250 000 copies/mL) in patients who did not clear CMV PCR than those who cleared (8000 copies/mL) after 14 d of treatment (p = 0.03). Risk factors and indirect CMV effects were not associated with initial QnPCR. Our results highlight the importance of the initial CMV QnPCR in relation to the development of symptomatic CMV and a slower response to therapy. Alternatively, late asymptomatic viremia and recurrent CMV are associated with lower PCR levels and a low likelihood to progress and result in clinical disease.
Subject(s)
Cytomegalovirus Infections/complications , Cytomegalovirus/pathogenicity , Transplants/virology , Viral Load , Adolescent , Adult , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Middle Aged , Polymerase Chain Reaction , Risk Factors , Transplants/adverse effects , Treatment Outcome , ViremiaABSTRACT
Nonmyeloablative allogeneic stem-cell transplantation (alloNST) is the focus of investigations searching for less-toxic transplantation regimens. We report studies on the kinetics of lymphodepletion and safety of pentostatin (PT) conditioning in alloNST. Patients with hematologic malignancy received mobilized blood from human leukocyte antigen-matched related (n=4) or unrelated (n=8) donors. PT 4 mg/m2 was administered on days -21, -20, and -19 and 200 cGy of total-body irradiation was administered on day -1, followed by cyclosporine A and mycophenolate mofetil. Mononuclear cell adenosine deaminase after PT was inhibited 84%. The absolute CD3+ cells decreased significantly by day -7 (49%) and CD19+ cells declined 92% by day -1. CD4+ cells were depressed more than CD8+ cells. Neutrophils and monocytes were minimally affected by PT. Median posttransplant peripheral blood chimerism on day 70 showed 95% donor leukocytes and 82.5% donor CD3 lymphocytes. PT demonstrated lymphodepleting effects and promising safety, supporting alloNST as early as 7 days after initiation of PT.