Oncology and transplant ID: July 2018

Autologous adoptive T-cell therapy for drug-resistant CMV infection was safe and effective in solid organ transplant patients in this small trial. T-cell therapy is quickly gaining traction for CMV and other viral infections in the immunocompromised ID world. Here the authors used autologous T cell therapy, meaning they extracted the patient’s own lymphocytes, expanded the CMV-specific T cells in vitro, then infused them back into the patient. Twenty-two transplant patients were included in this trial, all of whom had CMV infections that were either recurrent or resistant to gangciclovir. Autologous T cells manufacture was attempted in 21 cases and successful in all but one case; ultimately, 13 patients received the T cell therapy and the remainder received standard care. Of the patients receiving autologous T cells, 11/13 (84%) had clinical success, defined as improvement or resolution of symptoms of infection and/or CMV viremia, and cessation or reduced use of antivirals. Clinical success was associated with persistent elevation of CMV-specific T cells in peripheral blood after T-cell therapy. 29982441

A pre-emptive antifungal treatment strategy is as effective as empirical antifungal therapy for persistent febrile neutropenia in children with cancer and significantly reduces antifungal use. This was an RTC of 149 children with persistent high-risk febrile neutropenia conducted at five hospitals in Chile. In the in the empiric arm of the study, all patients received antifungal therapy starting on day four of febrile neutropenia; in the pre-emptive arm, antifungal therapy was given based on pre-defined criteria for clinical, laboratory, and radiographic evidence of fungal infection. Antifungal use was less frequent with the pre-emptive strategy (42% vs 100%) and given for a shorter duration (6 vs 11 days). Mortality was not significantly different between groups (8% for the pre-emptive arm vs 5% for the empirical arm), and mortality related to invasive fungal infection was identical (3% in both arms); duration of fever, duration of hospitalization, and rates of ICU admission were also similar. Importantly, this study excluded patients with hematopoietic stem cell transplants and those receiving voriconazole or posaconazole prophylaxis. 30010931

For children with acute leukemia undergoing hematopoietic stem cell transplantation, antibiotic use varies wildly between institutions and is not associated with mortality. This was a retrospective cohort study of 770 HSCT recipients at 27 children’s hospitals. The variable of interest was antibiotic use between day 0 of transplant and engraftment. Antibiotic use was expressed as days of therapy (DOT) per 1000 neutropenic patient-days, engraftment was defined as ANC >500 for 3 consecutive checks, and the primary outcome was mortality at 30 days. Antipseudomonal antibiotic usage ranged from 424 to 1012 DOT per 1000 neutropenic patient-days (median 713 DOT) and anti-MRSA antibiotic usage ranged from 148 to 824 DOT (median 399 DOT). Put another way, there was a 2.2 fold variation in gram-negative antibiotic use and a 5.7 fold variation in gram-positive antibiotic use. In multivariate analysis, patient demographics, disease severity, and hospital-level factors accounted for little of the interhospital variability in prescribing. Thirty-day mortality ranged from 0% to 10% (median 2%) and did not vary by level of antibiotic usage.

The striking differences in antibiotic use between hospitals even after adjustment for patient factors such as severity of illness, and the lack of improved mortality among the high-prescribing centers, suggests that antibiotic overprescribing for leukemia patients status-post HSCT is institutional and widespread. How do we change that? A pervasive problem in the immunocompromised ID world is that our patient population is seen as falling outside most of the guidelines. We say, “Our patients are sicker than the patients in the studies the recommendations are based on,” and then rely on eminence-based medicine. The solution, in my mind, is more research like this and eventually cancer and transplant center stewardship guidelines based on research in immunocompromised patients. 29734957

C. difficile infection is associated with solid organ graft loss. While we’re on the subject of antibiotic stewardship in immunocompromised patients, this is an important study from the American Journal of Transplantation. The authors reviewed the charts of 87 solid organ transplant recipients who developed C. difficile infection and 174 age/sex/organ-matched controls within a total cohort of 2158 solid organ recipients. CDI was most common in lung transplant (HR 1.48), least common in kidney transplant (HR 0.3), and associated with both infection (HR 2.8) and antibiotic use (HR 4.5) in the preceding 3 months. When CDI occurred posttransplant this was associated with graft loss (HR 2.2).

Could CDI merely be a surrogate marker for morbidity rather than a direct cause of graft loss? Certainly, and the authors mention that even mild CDI cases with good response to therapy were associated with graft loss. However, we know that the intestinal microbiome is an essential partner in maintaining gut barrier integrity. It’s biologically plausible that intestinal dysbiosis could lead to increased gut translocation of bacteria and their antigens into systemic circulation, increased systemic inflammation, and recruitment/stimulation of immune cells that could go on to cause graft rejection. 29349869

Now that Hepatitis C treatment is so easy to treat, why not let people with HCV infection donate their non-liver organs? That was the question asked in this cost-effectiveness analysis. The authors generated a decision model comparing the cost-effectiveness of transplanting a HCV-infected kidney into a HCV-infected recipient, then treating the HCV infection, versus treating the organ recipient’s HCV infection and then giving them a kidney from an uninfected donor. They predict that the transplant-and-treat approach would be more effective and less costly than the treatment first approach, mostly on account of longer wait times for an uninfected kidney. Seems to me that the cost-effectiveness calculation should also account for the decreased wait time for whoever ends up getting the HCV-uninfected kidney in the transplant-then-treat scenario, seeing as the main bottleneck in kidney transplantation is organ supply. That would shift the results even more in favor of using HCV-infected donor organs. 29987322