ORIGINAL ARTICLE
Safety and Outcomes of Extracorporeal Photopheresis With the Therakos Cellex System for Graft-Versus-Host Disease in Pediatric Patients Vedat Uygun, MD,*w Hayriye Daloglu, MD,w Gulsun Karasu, MD,*z Volkan Hazar, MD,y and Akif Yes¸ilipek, MD*w
Summary: Extracorporeal photopheresis (ECP) is a difficult procedure to perform in the pediatric population. This is a retrospective review of 12 pediatric patients who underwent photopheresis with the Therakos Cellex system for graft-versus-host disease (GVHD). Acute GVHD (aGVHD) occurred in 6 patients, and overlap syndrome and chronic GVHD (cGVHD) occurred in 4 and 2 patients, respectively. The ECP regimen was the same for all aGVHD and cGVHD patients: initially, every week (2 sessions/wk) for 2 months; next, every 2 weeks for 2 months; and finally, every month for at least 1 year. Improvement was observed in 7 of 10 aGVHD patients (70%) and in 4 of 6 cGVHD patients (66%). Eleven patients had skin involvement before ECP; 9 of them responded to treatment (81%). Gastrointestinal involvement occurred in 8 patients; 5 of them experienced improvement during ECP treatment (62%). All 4 patients with liver involvement failed to respond. No serious adverse reactions occurred. In conclusion, our study demonstrates that ECP with the Therakos Cellex system is a safe treatment option for GVHD in children, allowing the tapering of immunosuppressants by at least half. Key Words: extracorporeal photopheresis, graft-versus-host disease, apheresis
(J Pediatr Hematol Oncol 2015;37:209–214)
G
raft-versus-host disease (GVHD) is a serious complication with a significant negative impact on morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT) in both adults and children.1,2 Corticosteroids are universally accepted as the first-line treatment for GVHD. However, in patients with steroid-refractory GVHD, there is no consensus on second-line treatment options, which mostly consist of an array of immunosuppressants, such as Received for publication June 9, 2014; accepted October 3, 2014. From the *Bahc¸es¸ehir University School of Medicine; wMedical Park Antalya Hospital, Pediatric Hematology and Bone Marrow Transplantation Unit; yDepartment of Pediatric Hematology & Oncology, Akdeniz University School of Medicine, Antalya; and zBahc¸es¸ehir University School of Medicine, Medical Park Goztepe Hospital, Pediatric Hematology and Bone Marrow Transplantation Unit, Istanbul, Turkey. V.U.: data analysis/interpretation, drafting the article, approval of the article, statistics, data collection. H.D.: drafting the article, critical revision of the article, approval of the article, data collection. G.K.: critical revision of the article, approval of the article, data collection. V.H.: concept/design, critical revision of the article, approval of the article. A.Y.: concept/design, data analysis/interpretation, drafting the article, critical revision of the article, approval of the article. The authors declare no conflict of interest. Reprints: Vedat Uygun, MD, Bahc¸es¸ehir University School of Medicine, Medical Park Antalya Hospital, Pediatric Hematology and Bone Marrow Transplantation Unit, Muratpas¸a, Tekeliog˘lu Cd No: 7, Antalya 07070, Turkey (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
Volume 37, Number 3, April 2015
infliximab, rituximab, and alemtuzumab.3,4 GVHD is a multisystem disorder resembling an autoimmune disease that attacks major organs; therefore, immunosuppressants remain the mainstay of treatment. Nevertheless, immunosuppression carries risks of increased frequency of infections, a negative impact on the graft-versus-leukemia effect, and an increased probability of secondary malignancies.5–7 Extracorporeal photopheresis (ECP), proposed by various committees as a second-line treatment, seems to ameliorate GVHD by immunomodulation, rather than immunosuppression, hence carrying minimal risks regarding the aforementioned problems.8,9 The ECP process includes collecting mononuclear cells by leukopheresis; treating the buffy coat with photoactivatable drugs activated by UV light; and reinfusing the product into the patient, which results in apoptosis of the mononuclear cells, and mainly lymphocytes, in 24 to 72 hours. The induction of lymphocyte apoptosis results in reduced stimulation of effector T cells and induction of regulatory T cells. However, how ECP achieves these effects in GVHD is poorly understood and may well be multifactorial.9,10 Special considerations exist in the pediatric population, including limitations of peripheral lines, which are mostly handled by catheters, and for the tolerance to extracorporeal volume during leukopheresis. Therefore, the data on ECP in the pediatric population are scarce and generally based on studies with a small sample size.11–13 Because of the extracorporeal volume concerns, popular photopheresis systems are generally recommended only for patients >40 kg. There are certain modifications that can be made for pediatric patients
Safety and Outcomes of Extracorporeal Photopheresis With the Therakos Cellex System for Graft-Versus-Host Disease in Pediatric Patients Vedat Uygun, MD,*w Hayriye Daloglu, MD,w Gulsun Karasu, MD,*z Volkan Hazar, MD,y and Akif Yes¸ilipek, MD*w
Summary: Extracorporeal photopheresis (ECP) is a difficult procedure to perform in the pediatric population. This is a retrospective review of 12 pediatric patients who underwent photopheresis with the Therakos Cellex system for graft-versus-host disease (GVHD). Acute GVHD (aGVHD) occurred in 6 patients, and overlap syndrome and chronic GVHD (cGVHD) occurred in 4 and 2 patients, respectively. The ECP regimen was the same for all aGVHD and cGVHD patients: initially, every week (2 sessions/wk) for 2 months; next, every 2 weeks for 2 months; and finally, every month for at least 1 year. Improvement was observed in 7 of 10 aGVHD patients (70%) and in 4 of 6 cGVHD patients (66%). Eleven patients had skin involvement before ECP; 9 of them responded to treatment (81%). Gastrointestinal involvement occurred in 8 patients; 5 of them experienced improvement during ECP treatment (62%). All 4 patients with liver involvement failed to respond. No serious adverse reactions occurred. In conclusion, our study demonstrates that ECP with the Therakos Cellex system is a safe treatment option for GVHD in children, allowing the tapering of immunosuppressants by at least half. Key Words: extracorporeal photopheresis, graft-versus-host disease, apheresis
(J Pediatr Hematol Oncol 2015;37:209–214)
G
raft-versus-host disease (GVHD) is a serious complication with a significant negative impact on morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT) in both adults and children.1,2 Corticosteroids are universally accepted as the first-line treatment for GVHD. However, in patients with steroid-refractory GVHD, there is no consensus on second-line treatment options, which mostly consist of an array of immunosuppressants, such as Received for publication June 9, 2014; accepted October 3, 2014. From the *Bahc¸es¸ehir University School of Medicine; wMedical Park Antalya Hospital, Pediatric Hematology and Bone Marrow Transplantation Unit; yDepartment of Pediatric Hematology & Oncology, Akdeniz University School of Medicine, Antalya; and zBahc¸es¸ehir University School of Medicine, Medical Park Goztepe Hospital, Pediatric Hematology and Bone Marrow Transplantation Unit, Istanbul, Turkey. V.U.: data analysis/interpretation, drafting the article, approval of the article, statistics, data collection. H.D.: drafting the article, critical revision of the article, approval of the article, data collection. G.K.: critical revision of the article, approval of the article, data collection. V.H.: concept/design, critical revision of the article, approval of the article. A.Y.: concept/design, data analysis/interpretation, drafting the article, critical revision of the article, approval of the article. The authors declare no conflict of interest. Reprints: Vedat Uygun, MD, Bahc¸es¸ehir University School of Medicine, Medical Park Antalya Hospital, Pediatric Hematology and Bone Marrow Transplantation Unit, Muratpas¸a, Tekeliog˘lu Cd No: 7, Antalya 07070, Turkey (e-mail: [email protected]). Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
Volume 37, Number 3, April 2015
infliximab, rituximab, and alemtuzumab.3,4 GVHD is a multisystem disorder resembling an autoimmune disease that attacks major organs; therefore, immunosuppressants remain the mainstay of treatment. Nevertheless, immunosuppression carries risks of increased frequency of infections, a negative impact on the graft-versus-leukemia effect, and an increased probability of secondary malignancies.5–7 Extracorporeal photopheresis (ECP), proposed by various committees as a second-line treatment, seems to ameliorate GVHD by immunomodulation, rather than immunosuppression, hence carrying minimal risks regarding the aforementioned problems.8,9 The ECP process includes collecting mononuclear cells by leukopheresis; treating the buffy coat with photoactivatable drugs activated by UV light; and reinfusing the product into the patient, which results in apoptosis of the mononuclear cells, and mainly lymphocytes, in 24 to 72 hours. The induction of lymphocyte apoptosis results in reduced stimulation of effector T cells and induction of regulatory T cells. However, how ECP achieves these effects in GVHD is poorly understood and may well be multifactorial.9,10 Special considerations exist in the pediatric population, including limitations of peripheral lines, which are mostly handled by catheters, and for the tolerance to extracorporeal volume during leukopheresis. Therefore, the data on ECP in the pediatric population are scarce and generally based on studies with a small sample size.11–13 Because of the extracorporeal volume concerns, popular photopheresis systems are generally recommended only for patients >40 kg. There are certain modifications that can be made for pediatric patients
