Cohort and nested case-control study of cutaneous squamous cell carcinoma in solid organ transplant recipients, by medication.

BACKGROUND: Knowledge is needed about the risk of cutaneous squamous cell carcinoma (cSCC) in solid organ transplant recipients (SOTRs) using contemporary immunosuppressive regimens. OBJECTIVE: Evaluate the risk of cSCC in relation to medications used by SOTRs. METHODS: The cohort and nest case-control study included 3308 SOTRs and 65,883 persons without transplantation during 2009-2019. Incident cSCC was identified from pathology data, and medications were identified from pharmacy data. Adjusted hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards analysis, with voriconazole examined as a time-dependent variable. RESULTS: The annual incidence of cSCC was 1.69% in SOTRs and 0.30% in persons without transplantation. The adjusted hazard ratio of cSCC associated with lung transplant was 14.83 (95% CI, 9.85-22.33) for lung and 6.53-10.69 for other organs. Risk in Latinx persons was higher than in other non-White groups. Among lung recipients, the hazard ratio was 1.14 for each month of voriconazole use (95% CI, 1.04-1.26). Azathioprine use for ≥7 months, relating to mycophenolate mofetil intolerance, was associated with a 4.22-fold increased risk of cSCC (95% CI, 1.90-9.40). Belatacept and other immunsuppressive medications were not associated with risk. LIMITATION: The number of events was somewhat small. CONCLUSIONS: The knowledge of risks and benefits in diverse patients can translate to improvements in care.

Kidney disease associated with plasma cell dyscrasias.

Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Paraproteins can cause a remarkably diverse set of pathologic patterns in the kidney and recent progress has been made in explaining the molecular mechanisms of paraprotein-mediated kidney injury. Other recent advances in the field include the introduction of an assay for free light chains and the use of novel antiplasma cell agents that can reverse renal failure in some cases. The role of stem cell transplantation, plasma exchange, and kidney transplantation in the management of patients with paraprotein-related kidney disease continues to evolve.

Light chains: heavy burden in kidney transplantation.

Plasma cell dyscrasias are frequently encountered malignancies which are often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Recent advances in the field include the availability of an assay for free light chains, the introduction of new agents which more effectively target malignant plasma cells, and refinements in the application of stem-cell transplantation. Well-selected patients with plasma cell dyscrasias whose monoclonal Ig is well controlled may be candidates for kidney transplantation. Kidney transplant patients with allograft dysfunction from recurrent or de novo monoclonal Ig deposition can be successfully identified and treated with these new approaches.

HLA-mismatched renal transplantation without maintenance immunosuppression.

Five patients with end-stage renal disease received combined bone marrow and kidney transplants from HLA single-haplotype mismatched living related donors, with the use of a nonmyeloablative preparative regimen. Transient chimerism and reversible capillary leak syndrome developed in all recipients. Irreversible humoral rejection occurred in one patient. In the other four recipients, it was possible to discontinue all immunosuppressive therapy 9 to 14 months after the transplantation, and renal function has remained stable for 2.0 to 5.3 years since transplantation. The T cells from these four recipients, tested in vitro, showed donor-specific unresponsiveness and in specimens from allograft biopsies, obtained after withdrawal of immunosuppressive therapy, there were high levels of P3 (FOXP3) messenger RNA (mRNA) but not granzyme B mRNA.