Use of letermovir for cytomegalovirus primary prophylaxis in lung transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a driver of negative outcomes after lung transplant (LTX) and primary prophylaxis (PPX) with valganciclovir (VGC) is standard-of-care. VGC is associated with myelosuppression, prompting interest in letermovir (LTV). METHODS: Adults receiving LTX between April 1, 2015, and July 30, 2022, at our institution were evaluated. Patients were excluded if low CMV risk (D-/R-), survived <90 days post-LTX, or transferred care before PPX withdrawal. Primary outcomes were leukopenia (white blood cell count [WBC] ≤ 3.0 × 109/L), severe leukopenia (WBC ≤ 2.0 × 109/L), and neutropenia (absolute neutrophil count ≤ 1500 cells/µL) requiring granulocyte-colony stimulating factor (GCSF) on PPX. Secondary outcomes included breakthrough CMV infection and post-PPX CMV infection. RESULTS: 204 patients met inclusion criteria: 175 patients on VGC and 29 patients on LTV (after VGC conversion). Most patients received bilateral LTX (62.7%) with non-lymphocyte-depleting induction (96.6%) and moderate-risk serostatus (D+/R+, 48.5%). Patients transitioned from VGC to LTV after a mean of 178 days (SD 80.8 days) post-transplant. Patients on VGC experienced significantly more leukopenia (82.3% vs. 58.6%, p = 0.008), severe leukopenia (57.1% vs. 31.0%, p = 0.016), and neutropenia requiring GCSF (70.9% vs. 51.7%, p = 0.048). Breakthrough (5.7% vs. 3.4%, p = 0.955) and post-PPX (24.6% vs. 37.9%, p = 0.199) infections were similar. A subgroup analysis of patients with high-risk serostatus showed similar trends, though did not reach statistical significance. CONCLUSIONS: In this single-center study, the incidence of leukopenia and neutropenia requiring GCSF were reduced with LTV compared to VGC. Breakthrough and post-PPX infections were not significantly different. This evidence suggests that LTV has comparable efficacy with reduced myelosuppression compared to VGC in LTX recipients, and may be an appropriate alternative for PPX.

Diagnosis and treatment of antibody mediated rejection in lung transplantation: a retrospective case series.

INTRODUCTION: Antibody mediated rejection (AMR) has been identified as an entity that may lead to graft dysfunction. Optimal means for diagnosis and treatment of AMR have not been established. MATERIAL AND METHODS: We reviewed the medical records of all patients receiving lung transplantation at Henry Ford Hospital from March 2006 to December 2011. For each patient, we identified potential markers of AMR (immunopathology, histopathology, and serology). Immunopathology was defined as linear c4d immunostaining, histopathology was defined as capillaritis, and serology was defined as identification of donor specific antibody (DSA). We identified all treatment regimens, and we identified clinical and serological outcomes. RESULTS: Of 62 patients, 14 were identified with at least one marker of AMR. Only two patients had all three potential markers; immunopathology, histopathology, and serology. Both patients received plasmapheresis (PP) and intravenous immunoglobulin followed by clinical improvement and ultimate elimination of DSA. 4 patients had positive DSA without clinical symptoms, and did not receive treatment with PP, IVIG, or rituximab. DSA has not persisted in these patients, and they remain clinically asymptomatic at up to 803days after identification. DISCUSSION: Diagnosis of AMR is difficult due to poorly defined diagnostic markers and confounding factors such as infection. Outcomes are highly variable following treatment that may include therapeutic plasma exchange, intravenous immunoglobulin, and/or rituximab. It is not clear when any or all of these therapies are beneficial. In some cases, symptomatic patients with isolated positive DSA (latent humoral response) can remain asymptomatic and convert to negative DSA without antibody targeted therapy. CONCLUSIONS: Firm conclusions are difficult due to the small number of patients and the retrospective nature of the study. Further study is warranted.

Timing of basiliximab induction and development of acute rejection in lung transplant patients.

BACKGROUND: Acute rejection affects more than 36% of recipients within the first year post-transplantation. The interleukin-2 (IL-2) receptor antagonist basiliximab has been associated with decreased frequency and severity of acute rejection. We investigated whether the timing of induction administration would impact the frequency and severity of acute rejection in the first year after transplantation. METHODS: In this study we reviewed 119 patients who underwent lung transplantation at Henry Ford Hospital from October 1994 to January 2009. Prior to January 2000 no patients received induction. From January 2000 to March 2006 the initial dose was given after implantation, and from March 2006 to 2009 basiliximab was given prior to implantation. The primary outcome was cumulative acute rejection score (CAR) in the first post-operative year comparing post- vs pre-implant induction. RESULTS: The CAR score for pre-implant basiliximab was 2.5 ± 2.3. This was significantly lower than CAR score of 4.6 ± 3.9 in the post-implant group (p = 0.025). The no-induction group had the highest CAR score at 6.3 ± 3.8 (p = 0.077 compared with the post group). The mean follow-up times in the post and pre group were 5.9 ± 2.3 and 2.3 ± 0.7 years, respectively (p < 0.001). There was no difference in freedom from bronchiolitis obliterans syndrome (BOS), survival or invasive infections between pre- and post-implant induction groups. CONCLUSIONS: Basiliximab prior to implant is associated with a lower cumulative acute rejection score over 1 year compared with induction post-implantation. Despite a lower cumulative acute rejection score, there was no significant difference in freedom from BOS or survival.

Transfer of peanut allergy from the donor to a lung transplant recipient.

Among solid organs, transfer of peanut allergy from donor to recipient has been implicated after liver transplantation. We report the first case in which such transfer occurred after a lung transplant. A 42-year-old woman with history of sarcoidosis underwent a successful bilateral lung transplant from a donor who died from anaphylactic shock after eating peanut-related food. Seven months later, she ate a peanut butter cookie at a transplant support group meeting. Immediately thereafter, she developed an anaphylactic reaction, but survived with prompt treatment. During subsequent follow-up, she could recall three prior episodes of wheezing and difficulty breathing after eating peanut-related foods. The first episode occurred 4 days after the transplant. Prior to her transplant, she never had problems eating peanuts. Skin-prick testing confirmed peanut sensitization. She avoided peanuts and, although her skin-prick test became negative, she still manifested peanut allergy when formally challenged orally with the food. She was advised to continue abstaining from all peanut-related foods. This case emphasizes the importance of considering donor allergy transfer when caring for all solid-organ transplant recipients in order to avoid a life-threatening event.

Patient comfort during pressure support and volume controlled-continuous mandatory ventilation.

BACKGROUND: Pressure-support ventilation (PSV) is more comfortable than volume controlled-continuous mandatory ventilation (VC-CMV) in acute hypercapnic respiratory failure, in patients undergoing noninvasive ventilation. Physiologic measurements of patient status have been compared in PSV and VC-CMV in endotracheally intubated patients, but patient perception of comfort has not been measured in this population. OBJECTIVE: To determine if PSV is more comfortable than VC-CMV (volume-cycled, flow-limited) in intubated mechanically ventilated patients. METHODS: In a randomized prospective trial, patients underwent PSV and VC-CMV for 30 min each, separated by a 30 min washout with the baseline ventilation mode (pressure-regulated volume-control ventilation [PRVC]). The level of pressure support was set as the plateau pressure on VC-CMV with a tidal volume of 8 mL/kg minus the end-expiratory pressure. After each mode the patient was asked to mark his or her comfort level on a visual analog scale. RESULTS: Eleven of the 14 patients were more comfortable during PSV. The baseline mean comfort score (during PRVC) was 62 +/- 18 (95% confidence interval 51.7-72.5). The mean comfort score for PSV was 83 +/- 11 (95% confidence interval 76.9-89.6). The mean comfort score for VC-CMV was 70 +/- 18 (95% confidence interval 59.4-79.9). PSV was significantly more comfortable than VC-CMV (p = 0.02) or PRVC (p = 0.009), whereas the comfort scores for VC-CMV and PRVC were not significantly different (p = 0.278). Respiratory rate, blood pressure, heart rate, minute ventilation, and blood oxygen saturation showed no difference between PRVC, VC-CMV, and PSV. CONCLUSIONS: On average the patients felt more comfortable during PSV than during VC-CMV or PRVC, so PSV may be the preferred mode for awake intubated patients.