Acute Graft-Versus-Host Disease After Orthotopic Liver Transplantation: Predicting This Rare Complication Using Machine Learning.

Acute graft-versus-host disease (GVHD) is a rare complication after orthotopic liver transplantation (OLT) that carries high mortality. We hypothesized that machine-learning algorithms to predict rare events would identify patients at high risk for developing GVHD. To develop a predictive model, we retrospectively evaluated the clinical features of 1938 donor-recipient pairs at the time they underwent OLT at our center; 19 (1.0%) of these recipients developed GVHD. This population was divided into training (70%) and test (30%) sets. A total of 7 machine-learning classification algorithms were built based on the training data set to identify patients at high risk for GVHD. The C5.0, heterogeneous ensemble, and generalized gradient boosting machine (GGBM) algorithms predicted that 21% to 28% of the recipients in the test data set were at high risk for developing GVHD, with an area under the receiver operating characteristic curve (AUROC) of 0.83 to 0.86. The 7 algorithms were then evaluated in a validation data set of 75 more recent donor-recipient pairs who underwent OLT at our center; 2 of these recipients developed GVHD. The logistic regression, heterogeneous ensemble, and GGBM algorithms predicted that 9% to 11% of the validation recipients were at high risk for developing GVHD, with an AUROC of 0.93 to 0.96 that included the 2 recipients who developed GVHD. In conclusion, we present a practical model that can identify patients at high risk for GVHD who may warrant additional monitoring with peripheral blood chimerism testing.

Impaired graft survival in pediatric renal transplant recipients with donor-specific antibodies detected by solid-phase assays.

SAB assays have increased the sensitivity and specificity to detect HLA alloantibodies, but there is uncertainty about the clinical relevance of SAB-positive alloantibodies when the FCXM is negative. We performed a retrospective study to evaluate the clinical significance of SAB-detected DSA in 82 pediatric recipients of a first kidney transplant between January 2000 and December 2005 who had a negative pretransplant FCXM. Pretransplant sera were evaluated by SAB for DSA. Graft loss and rejection between patients with (DSA+) and without DSA (DSA-) were compared. DSA were detected in 13.9%. Eighty percent of DSA+ subjects were DD transplant recipients vs. 56.9% in the DSA- cohort. The RR of graft loss in DSA+ vs. DSA- was 3.3 (95% CI, 1.4-7.9) and in DD was 4.3 (95% CI 1.4-13.1). By Cox regression, the HR of graft loss in DSA+ vs. DSA- was 2.8 (95% CI 0.7-10.9; p = 0.14) and in DD was 5.1 (95% CI 1-25.6; p = 0.05). Acute rejection occurred in 60% in the DSA+ vs. 44.4% in DSA- (p = 0.5). SAB-detected DSA was associated with impaired renal allograft survival in pediatric renal transplant recipients. Impaired graft survival in pediatric renal transplant recipients with DSA detected by solid-phase assays.

ABO-incompatible solid-organ transplantation.

To increase transplantation access, particularly in living-donor renal transplantation, efforts have been made to overcome the barrier of ABO incompatibility. In adults, the most successful cases have involved renal transplantation. Although the overall goal of reducing antibodies against donor ABO before and after transplantation is a general principle, the protocols used to accomplish this goal vary. More well-designed, controlled clinical trials are needed to establish optimal peritransplantation management protocols. Incompatible liver transplantation still is viewed as a temporary measure until ABO-compatible transplantation can be performed. ABO-incompatible heart and lung transplantation in adults still is not performed intentionally. In children, particularly those with relatively immature immune systems, ABO-incompatible transplantation generally has more success. The immunologic mechanisms leading to successful transplantation are being elucidated. Accommodation is a process whereby the donor organ may participate in its own survival through a series of protective gene responses, possibly in response to low-level incompatible antibody (HLA and ABO). In infants, spontaneous, acquired B-cell tolerance seems to be a primary mechanism. Peritransplantation therapy might be tailored to invoke specific immune graft-sparing mechanisms. The stage is set to eliminate ABO as a barrier to solid-organ transplantation.