Allogeneic hematopoietic stem cell transplantation (HSCT) is the only widely available cure for sickle cell disease (SCD), yet its use in adults has historically been limited by transplant-related toxicity. Non-myeloablative (NMA) and reduced-intensity conditioning (RIC) regimens have addressed this by maintaining durable engraftment at considerably lower risk. The NIH NMA protocol, alemtuzumab plus 300 cGy total body irradiation, achieves overall survival (OS) above 90% in matched sibling transplants, with no chronic graft-versus-host disease (GVHD) and preserved fertility. Haploidentical transplantation has likewise matured; a thiotepa-based regimen with post-transplant cyclophosphamide (PTCy) yielded 2-year OS of 95% and graft failure of just 7% in a phase 2 multicenter trial, with mixed donor chimerism of at least 20% myeloid cells sufficient for phenotypic cure. Chronic GVHD incidence differs across platforms, from 0% with NMA conditioning, 13-22% with RIC, to 22% in the haploidentical plus PTCy setting, and non-relapse mortality follows a similar pattern at 0-5% and 5-10% across these groups. Survivors report meaningful improvements in quality of life, though infectious complications and secondary malignancies continue to warrant close follow-up. Taken together, the data support NMA and RIC transplantation as genuinely curative options carrying an acceptable risk profile for adults living with SCD, and advances in haploidentical conditioning have largely put to rest the graft failure rates that once made unrelated or mismatched transplantation prohibitive. How to best target chimerism levels, reduce late toxicity, and weigh transplant against the rapidly advancing field of gene therapy are questions the field has yet to fully resolve.

Infection-related complications, including urinary tract infections (UTIs) and urosepsis, account for a significant proportion of morbidity and mortality in patients with advanced multiple sclerosis (MS). However, the role of specific disease-modifying therapies (DMTs) in UTI and urosepsis risks remains underexplored. We identified 12,997 UTI and 651 urosepsis reports associated with various MS in the FDA Adverse Event Reporting System. Ocrelizumab exhibited the greatest safety signal for UTI, while natalizumab, alemtuzumab, and interferon beta-1a were also associated with disproportionately high reporting across sex and age subgroups. Thus, clinicians should maintain UTI vigilance and integrate proactive bladder management in routine MS care.

Optimizing immunosuppressive therapy remains central to improving long-term outcomes after kidney transplantation. Both induction and maintenance therapies are widely used, yet their comparative effectiveness across diverse recipient populations requires further evaluation. This national retrospective cohort study analyzed 228,855 deceased-donor kidney transplant recipients using data from 2000-2024. Multivariable Cox proportional hazards (PH) models were used for clinical inference, and four machine learning (ML) survival models: random survival forest (RSF), support vector machine (SVM), penalized Cox regression (CoxNet), and extreme gradient boosting optimized with the Cox partial likelihood (XGBoost-Cox), were developed to assess predictive performance for death-censored graft failure and all-cause patient mortality. Model performance was evaluated using the concordance index (C-index) and time-dependent area under the curve (tdAUC). Maintenance regimens incorporating calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF) were associated with lower hazards for both graft failure (CNI + MMF: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.70-0.74; CNI + MMF+steroids: HR 0.84, 95% CI 0.82-0.87) and patient mortality (CNI + MMF: HR 0.78, 95% CI 0.76-0.81; CNI + MMF+steroids: HR 0.90, 95% CI 0.88-0.93). Among induction therapies, antithymocyte globulin (ATG) was associated with lower hazards for both outcomes, whereas interleukin-2 receptor (IL-2R) antagonists and Alemtuzumab demonstrated neutral associations. Combined ATG + IL-2R therapy was associated with higher hazard of graft failure (HR 1.09). Recipient diabetes, dialysis dependence, older age, and higher Kidney Donor Profile Index were strong adverse predictors. Traditional Cox regression achieved robust discrimination (graft failure C-index: 0.685; patient mortality C-index: 0.704), comparable to ML survival models. These findings support the continued association of CNI and MMF maintenance regimens with favorable long-term transplant outcomes while demonstrating variation across induction strategies. The dual analytical framework integrating classical Cox modeling with ML survival methods, suggests that Cox models remain highly competitive for clinical inference, whereas ML approaches provide complementary predictive value to support individualized post-transplant risk stratification.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal disorder characterized by immune hyper-activation and subsequent tissue and organ infiltration by proinflammatory cytokines. Primary HLH is caused by underlying genetic mutations in key genes responsible for cellular cytotoxicity, whereas secondary HLH is driven by infection, malignancy, and autoimmune disease as the underlying trigger for immune activation. Chemotherapy-based treatments for pediatric HLH have improved survival and outcomes for patients, however, there is a significant unmet need in the development of targeted therapies to limit drug toxicity and further improve overall survival.

The therapeutic arsenal of immunosuppressive drugs in kidney transplantation has recently expanded with the introduction of biologics, approved or used off-label, that specifically target the immune system. Although therapeutic drug monitoring is well established for calcineurin inhibitors, its utility for biological immunosuppressants remains unclear. The objective of this narrative review was to evaluate whether biologics used to prevent or treat renal allograft rejection could be suitable candidates for therapeutic drug monitoring. This review provides (1) a comprehensive and up-to-date synthesis on the pharmacological targets of biologics used in kidney transplantation, (2) assesses the interindividual variability of the pharmacokinetics and pharmacokinetic/pharmacodynamic relationships of key biologics, including belatacept, tocilizumab, rituximab, basiliximab, alemtuzumab, eculizumab, ravulizumab, daratumumab, and imlifidase and (3) describes the analytical methods available for their quantification. This review underscores that, although none of these biologics currently meet all criteria for routine therapeutic drug monitoring, emerging clinical evidence indicates that individualized dosing could enhance both therapeutic outcomes and cost effectiveness. It also discusses future directions for improving pharmacokinetic/pharmacodynamic knowledge on biological therapies in kidney transplant recipients and places in perspective the potential of therapeutic drug monitoring to improve the benefit-risk ratio and cost effectiveness of these biologics.