Roberta Sebastiani

Successful treatment of a classic Hodgkin lymphoma-type post-transplant lymphoproliferative disorder with tailored chemotherapy and Epstein-Barr virus-specific cytotoxic T lymphocytes in a pediatric heart transplant recipient.

CHL type is the least common major form of EBV‐related PTLD but rarely occurs in pediatric recipients; development of CHL subsequent to other PTLD subtypes in the same transplant recipient is even more unusual. Because of its rarity, indications on the best treatment strategy are limited. Patients have been mostly treated with standard HL chemotherapy/radiotherapy, and prognosis seems more favorable than other monomorphic PTLDs. Herein, we describe a pediatric case of EBV‐associated, stage IV‐B, CHL arising in a heart allograft recipient eight yr after diagnosis of B‐cell polymorphic PTLD. The patient was successfully treated with adjusted‐dose HL chemotherapy and autologous EBV‐specific CTL, without discontinuation of maintenance immunosuppression. At two yr from therapy completion, the patient is in CR with stable organ function. With this strategy, it may be possible to reproduce the good prognostic data reported for CHL‐type PTLD, with decreased risk of organ toxicity or rejection.

Heterotopic heart transplantation for elevated pulmonary vascular resistance in the current era: Long-term clinical and hemodynamic outcomes

biopsies performed, only 42 cases of MPMNs were identified in allograft lungs. Because of their small size and the need to recut paraffin blocks to perform chimerism studies, only 2 of our 6 gender-mismatched recipients were available for study, but they provided convincing evidence that this cellular proliferation arises from the donated graft. This observation confirms earlier studies published in this journal that utilized primarily clinical data to arrive at this conclusion.

Risk-adapted Treatment for Severe B-Lineage Posttransplant Lymphoproliferative Disease After Solid Organ Transplantation in Children.

Background Optimal management of posttransplant lymphoproliferative disease (PTLD) remains to be defined due to heterogeneity of this condition and lack of predictors of the outcome. Here we report our experience with pediatric PTLD nonresponsive to immunosuppression (IS) withdrawal, managed after stratification into high and low risk according to the presenting features. Methods This is a single-center retrospective review of prospectively enrolled patients. From 2001 to 2011, 17 children were diagnosed with severe B-lineage, CD20+, PTLD after a median of 37 months (range, 5–93) from liver (12), heart (4), or multiorgan (1) transplantation. Treatment was tailored on 2 risk groups: (1) standard-risk (SR) patients received IS reduction and rituximab; (2) high-risk (HR) patients received IS discontinuation, rituximab and polychemotherapy. Results The cumulative incidence of rejection at 1 and 5 years after the diagnosis of PTLD was 35% (95% confidence interval [95% CI], 18-69%) and 53% (33-85%), respectively, whereas the disease-free survival at 1 and 5 years was 94% (95% CI, 65-99%) and 75% (45-90%), respectively. Three children died, PTLD-free, from different transplant-related complications: primary nonfunction after retransplantation (liver), cytomegalovirus disease 21 months after PTLD treatment (liver), graft dysfunction 25 months after PTLD (heart). Conclusions Severe B-lineage PTLD after solid organ transplantation may be classified as SR or HR and treated accordingly with a tailored protocol obtaining a satisfactory long-term outcome. This approach accomplishes the control of lymphoproliferation in severe forms as well as the minimization of toxicity in milder PTLDs.

The unnatural history of failing univentricular hearts: outcomes up to 25 years after heart transplantation

OBJECTIVES Heart transplantation (HTx) in children with a univentricular physiology is a challenge. In this study, we aimed to investigate the early and late survival as well as the causes of death of HTx recipients at different stages of univentricular palliation. METHODS Between January 1987 and September 2015, 40 orthotropic cardiac transplants were performed in 38 children with univentricular hearts at our institution. Outcomes were reviewed using medical records and transplant databases. RESULTS For the purposes of this analysis, patients were divided into 3 subgroups according to their stage of palliation: Stage 1 (n = 10, 26%), Stage 2 (n = 5, 13%) and Fontan (n = 23, 61%). The median age at HTx was 15.2 years (range 0-38). The median follow-up time after transplantation was 8.7 years (range 0-25.4). Indications for transplant were ventricular dysfunction in 25 (66%) patients, protein losing enteropathy in 10 patients transplanted in Fontan (26%) and refractory arrhythmias in 3 (8%) patients with an atriopulmonary connection. Total mortality was 42% (4.84/100 patient-years), and total early mortality was 21%. Overall survival at 1, 10 and 20 years was 73% (95% confidence interval 56-84%), 58% (95% confidence interval 40-72%) and 49% (95% confidence interval 30-65%), respectively. CONCLUSIONS HTx is a feasible option for patients with failing univentricular circulation, and although the mortality rate is high, this rate is still comparable to that in patients undergoing HTx for other congenital and non-congenital heart diseases.

Everolimus-Based Immunosuppression Improves Renal Function in Long-Term Heart Transplanted Patients: Five Years Results of a Prospective Randomized Trial

Purpose Renal insufficiency is a leading cause of morbidity and mortality after heart transplantation (Htx). CyA-based immunosuppression may contribute to kidney disease and a reduction of CyA seems reasonable. We aimed to assess whether changing from a CyA- to an Everolimus-based (EVL) immunosuppression can reduce the incidence of renal insufficiency in long-term Htx pts. We compared, in a prospective randomized trial, a reduction of >75% of CyA dose and EVL administration with conventional treatment. Methods and Materials Randomization was stratified by age, creatinine, gender and f-up in 213 pts >18 yrs (1-20 yrs of f-up, median 9). They were assigned to CyA reduction + EVL (n=108) or conventional treatment (n=105). At enrollment, 6 months, 1, 2, 3, 4 and 5 yrs f-up we estimated MDRD, creatinine, albuminuria, dialysis, and clinical outcome. An improvement in renal function was defined as an increase of > than 5 ml/min in MDRD. Results At entry, the two groups were similar. Eleven deaths were observed in each group. Renal function worsened in the conventional treatment pts. Mean creatinine (1,6±0,6) increased to 1,7±0,8 after 5 yrs in the control group and decreased to 1,5±0,86 in the EVL group (p = 0,01). MDRD improved from 55±24 to 64±34 ml/min (p Conclusions Conversion of a CyA- to EVL-based immunosuppression improves 5 yrs renal function in patients without proteinuria. Survival is not affected. This practice may be harmful for kidney function in the presence of heavy proteinuria.