Impacto de la variabilidad intrapaciente en la concentración sanguínea de anticalcineurínicos en los resultados del trasplante cardiaco / Impact of intrapatient blood level variability of calcineurin inhibitors on heart transplant outcomes

Introducción y objetivos: El objetivo es estudiar el impacto clínico de la variabilidad intrapaciente (VIP) de la concentración sanguínea de los anticalcineurínicos en el trasplante cardiaco, pues la información actual es escasa. Métodos: Se analizó retrospectivamente a pacientes de edad≥18 años con un trasplante cardiaco realizado entre 2000 y 2014 y con supervivencia≥1 año. La VIP se valoró mediante el coeficiente de variación de concentraciones entre los meses 4 a 12 postrasplante. El compuesto de rechazo, mortalidad o pérdida del injerto y la mortalidad o pérdida del injerto 1-5 años tras el trasplante se analizaron mediante regresión de Cox. Resultados: Se estudió a 1.581 receptores (edad, 56 años; mujeres, 21%), tratados con ciclosporina (790 pacientes) o tacrolimus (791 pacientes). En el análisis multivariable, un coeficiente de variación> 27,8% tendió a asociarse con el compuesto de rechazo/mortalidad (HR=1,298; IC95%, 0,993-1,695; p=0,056) y con la mortalidad (HR=1,387; IC95%, 0,979-1,963; p=0,065) a los 5 años. La asociación con el rechazo fue significativa al analizar a la población sin rechazos durante el primer año del trasplante (HR=1,609; IC95%, 1,129-2,295; p=0,011). El tacrolimus tuvo menos VIP que la ciclosporina, junto con unos mejores resultados por la menor influencia de la VIP. Conclusiones: La VIP de los anticalcineurínicos, especialmente con la inmunosupresión basada en el tacrolimus, se asocia solo marginalmente con los resultados a medio plazo del trasplante cardiaco, aunque puede tener influencia en los pacientes más estables durante el primer año tras el trasplante (AU)

Introduction and objectives: Intrapatient blood level variability (IPV) of calcineurin inhibitors has been associated with poor outcomes in solid-organ transplant, but data for heart transplant are scarce. Our purpose was to ascertain the clinical impact of IPV in a multi-institutional cohort of heart transplant recipients. Methods: We retrospectively studied patients aged ≥18 years, with a first heart transplant performed between 2000 and 2014 and surviving≥ 1 year. IPV was assessed by the coefficient of variation of trough levels from posttransplant months 4 to 12. A composite of rejection or mortality/graft loss or rejection and all-cause mortality/graft loss between years 1 to 5 posttransplant were analyzed by Cox regression analysis. Results: The study group consisted of 1581 recipients (median age, 56 years; women, 21%). Cyclosporine immediate-release tacrolimus and prolonged-release tacrolimus were used in 790, 527 and 264 patients, respectively. On multivariable analysis, coefficient of variation> 27.8% showed a nonsignificant trend to association with 5-year rejection-free survival (HR, 1.298; 95%CI, 0.993-1.695; P=.056) and with 5-year mortality (HR, 1.387; 95%CI, 0.979-1.963; P=.065). Association with rejection became significant on analysis of only those patients without rejection episodes during the first year posttransplant (HR, 1.609; 95%CI, 1.129-2.295; P=.011). The tacrolimus-based formulation had less IPV than cyclosporine and better results with less influence of IPV. Conclusions: IPV of calcineurin inhibitors is only marginally associated with mid-term outcomes after heart transplant, particularly with the tacrolimus-based immunosuppression, although it could play a role in the most stable recipients (AU)

The falling incidence of hematologic cancer after heart transplantation.

BACKGROUND: A number of changes in the management of heart transplantation (HT) patients have each tended to reduce the risk of post-HT hematologic cancer, but little information is available concerning the overall effect on incidence in the HT population. METHODS: Comparison of data from the Spanish Post-Heart-Transplantation Tumour Registry for the periods 1991-2000 and 2001-2010. RESULTS: The incidence among patients who underwent HT in the latter period was about half that observed in the former, with a particularly marked improvement in regard to incidence more than five yr post-HT. CONCLUSIONS: Changes in HT patient management have jointly reduced the risk of hematologic cancer in the Spanish HT population. Long-term risk appears to have benefited more than short-term risk.

Influence of steroid dosage, withdrawal, and reinstatement on survival after heart transplantation: results from the RESTCO study.

BACKGROUND: Little information is available regarding the consequences of steroid withdrawal following heart transplantation (HT) in Spain. METHODS: We analyzed the records of 1068 patients (81.6% men) who underwent HT between 2000 and 2005 in 13 Spanish centers who were aged ≥ 18 years and who survived at least 1 year. Death rates and Kaplan-Meier survival curves for 1 to 5 years post-HT were compared among four groups: groups A and B, patients on steroids throughout the first 5 years post-HT at dosages of ≤ 5 mg/d between 1-year and 5-year follow-up (group A; n = 148), or >5 mg/d for some part of this period (group B; n = 578). Groups C and D were patients from whom steroids were at some point withdrawn including group D (n = 73) with and group C (n = 269) without subsequent reintroduction into the maintenance regimen. RESULTS: Steroids were withdrawn at 1.6 ± 0.9 years post-HT in group C, and 1.7 ± 1.2 years post-HT in group D. The death rate between 1- and 5-year follow-up (deaths per 1000 person-years) was 44.3% (95% confidence interval 26.2-62.5) in group A, 42.6% (33.7-51.4) in group B, 30.5% (19.6-41.4) in group C, and 47.8% (21.8-73.7) in group D. There was no significant difference among them or among Kaplan-Meier survival curves of the four groups (P = .34 in both cases). Comparison of combined groups C + D with groups A + B showed no evidence of a greater mortality among combined groups C + D. CONCLUSIONS: The late withdrawal of steroids following HT was not associated with increased mortality.

Lung cancer after heart transplantation: results from a large multicenter registry.

In this study we analyzed Spanish Post-Heart-Transplant Tumour Registry data for adult heart transplantation (HT) patients since 1984. Median post-HT follow-up of 4357 patients was 6.7 years. Lung cancer (mainly squamous cell or adenocarcinoma) was diagnosed in 102 (14.0% of patients developing cancers) a mean 6.4 years post-HT. Incidence increased with age at HT from 149 per 100 000 person-years among under-45s to 542 among over-64s; was 4.6 times greater among men than women; and was four times greater among pre-HT smokers (2169 patients) than nonsmokers (2188). The incidence rates in age-at-diagnosis groups with more than one case were significantly greater than GLOBOCAN 2002 estimates for the general Spanish population, and comparison with published data on smoking and lung cancer in the general population suggests that this increase was not due to a greater prevalence of smokers or former smokers among HT patients. Curative surgery, performed in 21 of the 28 operable cases, increased Kaplan-Meier 2-year survival to 70% versus 16% among inoperable patients.

The prognosis of noncutaneous, nonlymphomatous malignancy after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.

INTRODUCTION: Malignancy is a major complication in the management of solid organ transplant patients. Skin cancers show a better prognosis than other neoplasms, but not all others are equal: Ideally, patient management must take into account the natural history of each type of cancer in relation to the transplanted organs. We sought to determine the prognosis of various groups of noncutaneous nonlymphomatous (NCNL) cancers after heart transplantation (HT). METHODS: We retrospectively analyzed the records of the Spanish Post-Heart-Transplant Tumour Registry, which collects data on posttransplant tumors in all patients who have undergone HT in Spain since 1984. Data were included in the study up to December 2008. We considered only the first NCNL post-HT tumors. RESULTS: Of 4359 patients, 375 developed an NCNL cancer. The most frequent were cancers of the lung (n=97; 25.9%); gastrointestinal tract (n=52; 13.9%); prostate gland (n=47; 12.5%; 14.0% of men), bladder (n=32; 8.5%), liver (n=14; 3.7%), and pharynx (n=14; 3.7%), as well as Kaposi's sarcoma (n=11; 2.9%). The corresponding Kaplan-Meier survival curves differed significantly (P<.0001; log-rank test), with respective survival rates of 47%, 72%, 91%, 73%, 36%, 64%, and 73% at 1 year versus 26%, 62%, 89%, 56%, 21%, 64%, and 73% at 2 years; and 15%, 51%, 77%, 42%, 21%, 64%, and 52% at 5 years post-diagnosis, respectively. CONCLUSION: Mortality among HT patients with post-HT NCNL solid organ cancers was highest for cancers of the liver or lung (79%-85% at 5 years), and lowest for prostate cancer (23%).