Donor screening for human T-cell lymphotrophic virus 1/2: changing paradigms for changing testing capacity.

Organ Procurement and Transplant Network (OPTN) policy currently requires the testing of all potential organ donors for human T-cell lymphotrophic virus (HTLV)-1/2. Most Organ Procurement Organizations (OPO) use the Abbott HTLV-I/HTLV-II Enzyme Immunoassay (EIA). This assay will no longer be manufactured after December 31, 2009; the only commercially available FDA-licensed assay will be the Abbott PRISM HTLV-I/II assay which poses many challenges to OPO use for organ donor screening. As a result, screening donors for HTLV-1/2 in a timely manner pretransplant after December 31, 2009 will be challenging. The true incidence of HTLV-1 in United States (U.S.) organ donors is not well described but appears to be low ( approximately 0.03-0.5%). HTLV-1 is associated with malignancy and neurological disease; HTLV-2 has not been convincingly associated with disease in humans. Donors that are HTLV-1/2 seropositive are infrequently used despite most results being either false positive or resulting from HTLV-2 infection. There is urgent need to encourage the development of assays, instruments and platforms optimized for organ donors that can be used to screen for transmissible disease in donors; these must have appropriate sensitivity and specificity to identify all infections while minimizing organ loss through false positive testing.

Fatal graft-versus-host disease presenting as fever of unknown origin in a pancreas-after-kidney transplant recipient.

Acute graft-versus-host disease (GVHD) is a rare complication of pancreas transplantation. We describe a 54-year-old male with type 1 diabetes who received a zero-antigen mismatched pancreas-after-kidney transplant from a pancreas donor who was homozygous at the HLA-B, -Cw, -DR, and -DQ alleles. Starting on postoperative day (POD) #22, the patient developed persistent fevers. Workup was notable only for low-grade cytomegalovirus viremia, which was treated. The fevers eventually disappeared. On POD #106, the patient was noted to have a diffuse erythematous rash. A skin biopsy was consistent with GVHD. Short tandem repeat DNA analysis of both peripheral blood lymphocytes and skin demonstrated mixed chimerism, confirming the diagnosis of GHVD. Soon after diagnosis, the patient developed pancytopenia and fevers and died of multiorgan failure on POD #145. Transplant clinicians should consider GVHD as a possible, although admittedly rare, cause of fevers of unknown origin in recipients of pancreas transplants.

Renal transplantation in patients with pre-transplant donor-specific antibodies and negative flow cytometry crossmatches.

The clinical significance of pre-transplant donor-specific antibodies (DSA), despite negative cytotoxicity and flow cytometry crossmatches (FCXMs), is unknown. We performed a retrospective cohort study of 60 living donor renal transplant recipients, all with pre-transplant cytotoxicity and T-cell and B-cell FCXMs that were negative. Twenty recipients had pre-transplant DSA detected by enzyme-linked immunosorbent assays (ELISA) and/or microbead methods. Forty contemporaneous DSA-negative controls were selected. In the DSA-positive group, after a median follow-up of 8.2 months (25-75% range, 5.4-22.8 months), patient survival was 100% and allograft survival was 95.0%. Acute humoral rejection (AHR) developed in four patients (20.0%). Three of the AHR episodes occurred within the first month post-transplant. Median serum creatinine at last follow-up was 1.3 mg/dL (25-75% range, 1.0-1.6 mg/dL), versus 1.1 mg/dL (25-75% range, 0.9-1.4 mg/dL) in the DSA-negative controls (p = 0.29). Only one of the 40 controls developed AHR (2.5%). Pre-transplant DSA was associated with a significantly increased incidence of AHR (p = 0.02 by log-rank test). In conclusion, despite negative pre-transplant cytotoxicity and FCXMs, renal transplant recipients with pre-transplant DSA detected by solid-phase methods may have an increased incidence of AHR and require close monitoring post-transplant.