Analysis of Clinical Outcome and Survival in Pediatric Patients Undergoing Extracorporeal Photopheresis for the Treatment of Steroid-refractory GVHD

Abstract

Extracorporeal photopheresis (ECP) has been used for treatment of steroid-refractory graft-versus-host disease (GVHD) with encouraging results. However, only a few pediatric centers have experienced with ECP, mainly by technical difficulties of leukapheresis in children. We retrospectively analyzed 27 patients treated during 5 years with ECP for steroid-refractory acute and chronic GVHD. We performed an "off-line" approach using a continuous flow cell separator (Cobe Spectra) and a Ultraviolet A irradiator (UVAMATIC). Among acute GVHD patients, 11 of 21 obtained a complete remission (CR) and another 8 reached partial remission. In the chronic GVHD group, 3 patients obtained CR and another 2 were in partial remission. Disease-free survival probability was 43±9% in the whole group. The only variable that impacts on disease-free survival on multivariate analysis was achieving CR with ECP. We also found a better CD4/CD8 ratio after ECP. In detail, among CD4 lymphocyte population, an increase in the effector memory and T-regulatory population was found. We may conclude that ECP is a safe and effective steroid-refractory GVHD treatment using the ex-vivo collection method, even in small children. Clinical response favorably impacts on long-term survival and seems to be associated with peripheral blood lymphocyte subset changes generating peripheral tolerance.

Treatment of Pediatric Acute Graft-versus-Host Disease—Lessons from Primary Immunodeficiency?

“…The clinical efficacy, safety, and tolerability of ECP in the treatment of aGvHD in patients have been demonstrated in several studies, which also show the steroid-sparing effect (82–85). A systematic analysis of prospective studies examining ECP treatment outcomes in corticosteroids refractory/dependent/intolerant aGvHD in adults and children found an overall response rate of almost 70% in all organs, an encouraging result compared to other second-line treatments used (86).…”

Extracorporeal photopheresis in pediatric patients: Practical and technical considerations

“…ASFA also acknowledges ECP as a second‐line therapy, either as a standalone treatment or in conjunction with other therapies, for cellular/recurrent rejection and rejection prophylaxis in cardiac transplants, as well as acute and chronic graft‐versus‐host disease (GVHD) . Published retrospective experience utilizing ECP in pediatric patients has focused on the management of acute and chronic GVHD, most often when refractory to first‐line therapies . No randomized controlled trials investigating ECP in pediatric patients have been published to‐date.…”

“…In the United States, this off‐line method has largely fallen out of favor following the development of automated systems . Of note, many ECP case series in pediatric patients utilized the COBE Spectra/UV‐MATIC technology (Tables and ) …”

“…Published pediatric case series vary widely in their recommendations for pre‐procedural transfusions (Table ). For the UVAR XTS and CELLEX systems, the patient's hematocrit (Hct) must be >27% in order to program the machines for effective buffy coat collection.…”

“…The most commonly reported adverse effects include hypotensive episodes, mild fever during reinfusion, and lethargy following the procedure for 1–2 days . In the reviewed pediatric literature, the most commonly reported adverse events include hypotension (range 0–27%), catheter‐related infections (range 0–42%), and abdominal pain (range 0–20%) (Table ). In addition, smaller patients (<20 kg) seemed to be at a greater risk of developing adverse events, most commonly hypotension, likely related to their extracorporeal volume constituting a greater fraction of total blood volume.…”