We report on a prospective phase II trial of 32 patients who underwent unrelated donor hematopoietic cell transplantation, with a tacrolimus, sirolimus and rabbit anti-thymoctye globulin GVHD prophylactic regimen. The primary study endpoint was incidence of grades II-IV acute GVHD, with 80% power to detect a 30% decrease compared to institutional historical controls. Median age at transplant was 60 (19-71). Twenty-three patients (72%) received reduced-intensity conditioning, while the remainder received full-intensity regimens. Median follow up for surviving patients was 35 months (range: 21 - 49). The cumulative incidence of acute GVHD was 37.3% and the 2-year cumulative incidence of cGVHD was 63%. We observed TMA in seven patients (21.8%), one of whom also developed sinusoidal obstructive syndrome (SOS). Four patients of 32 (12.5%) failed to engraft, and three of these four died. As a result, enrollment to this trial was closed before the targeted accrual of 60 patients. Two-year overall survival was 65.5% and event-free survival was 61.3%. Two-year cumulative incidence of relapse was 12.5% and non-relapse mortality (NRM) was 15.6%. NRM and aGVHD rates were lower than historical rates; however, the unexpectedly high incidence of graft failure requires caution in the design of future studies with this regimen.

BackgroundBecause of improved long-term survival after heart transplantation (HTx), late graft pathologies such as valvular disease or cardiac allograft vasculopathy (CAV) might need surgical intervention to enhance longer survival and ensure quality of life. To this date, there exist no guidelines for indication of cardiac surgery other than retransplantation after HTx.MethodsIn this retrospective, single-center study, we evaluated patients who underwent cardiac surgery after HTx at our institution.ResultsBetween March 1984 and October 2016, 17 (1.16%) of 1466 HTx patients underwent cardiac surgery other than retransplantation after HTx. Indication were valvular disease (n = 7), CAV (n = 6), and other (n = 4). Of these, 29.4% (n = 5) were emergency procedures and 70.6% were elective cases. Median age at time of surgery was 61 years (interquartile range, 52-66 years); 82.4% (n = 14) were male. Median time to surgery after HTx was 9.3 years (2.7-11.1 years). In-hospital, mortality was 11.8% (n = 2); later need of retransplantation was 11.8% (n = 2) due to progressing CAV 3 to 9 months after surgery. One-year survival was 82.35%; overall survival was 47.1% (n = 8) with a median follow-up of 1477 days (416-2135 days). Overall survival after emergency procedures was 209 days (36-1119.5 days) whereas, for elective procedures, it was 1583.5 days (901.5-4319 days).ConclusionsIncidence of cardiac surgery after HTx in our cohort was low (1.16%) compared with that of other studies. In elective cases, long-term survival was good.

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ObjectivesDespite the evident shift toward biological prostheses, the optimal choice of valve remains controversial in composite valve graft (CVG) replacement. We investigated long-term morbidity and mortality after CVG implantation in an all-comer cohort with a subgroup analysis of patients aged 50–70 years stratified after valve type.MethodsA total of 507 patients underwent the Bentall procedure with either a mechanical (MCVG, n = 299) or a biological (BCVG n = 208) CVG replacement between 2000 and 2020. A single-center analysis comprising clinical and telephone follow-up was conducted to investigate late mortality and morbidityResultsThe 30-day mortality in all patients [age 56 ± 14 years, 78.1% male, EuroSCORE II 3.12 (1.7; 7.1)] was 5.9%. Patients who were electively operated on had a 30-day mortality of 1.5% (n = 5) while it remained higher in urgent/emergent procedures (n = 25, 15.4%). Survival at 10 and 15 years was 78.19 ± 2.26% and 72.6 ± 3.2%, respectively. In patients aged 50–70 years (n = 261; MCVG = 151, BCVG = 110), survival did not differ significantly between the valve groups (p = 0.419). Multivariable analysis showed no significant impact of valve type on survival (p = 0.069). A time-varying relation with survival was notable, showing a higher risk in the MCVG group in the early postoperative phase, which declined compared to the BCVG group in the course of follow-up.ConclusionsThe Bentall technique presents with excellent mortality when performed electively. The type of valve prosthesis showed no statistically significant effect on mortality in patients aged 50–70 years. However, a time-varying relation showing an initially higher risk with MCVG which decreased compared to BCVG at long-term follow-up was notable. Further studies with even longer follow-up of BCVGs will clarify the ideal choice of prosthesis in this patient subset.

In severely ill patients undergoing urgent heart transplant (HTX), immunosuppression carries high risks of infection, malignancy, and death. Low-dose immunosuppressive protocols have higher rejection rates. We combined extracorporeal photopheresis (ECP), an established therapy for acute rejection, with reduced-intensity immunosuppression. Twenty-eight high-risk patients (13 with high risk of infection due to infection at the time of transplant, 7 bridging to transplant via extracorporeal membrane oxygenation, 8 with high risk of malignancy) were treated, without induction therapy. Prophylactic ECP for 6 months (24 procedures) was initiated immediately postoperatively. Immunosuppression consisted of low-dose tacrolimus (8–10 ng/ml, months 1–6; 5–8 ng/ml, >6 months) with delayed start; mycophenolate mofetil (MMF); and low maintenance steroid with delayed start (POD 7) and tapering in the first year. One-year survival was 88.5%. Three patients died from infection (POD 12, 51, 351), and one from recurrence of cancer (POD 400). Incidence of severe infection was 17.9% (n = 5, respiratory tract). Within the first year, antibody-mediated rejection was detected in one patient (3.6%) and acute cellular rejection in four (14.3%). ECP with reduced-intensity immunosuppression is safe and effective in avoiding allograft rejection in HTX recipients with risk of severe infection or cancer recurrence.