Etanercept as Treatment of Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric Patients

Abstract

A B S T R A C T Corticosteroids are the standard of care for first-line treatment of patients who develop grade II-IV of acute graftversus-host disease (aGVHD), but the optimal second-line treatment has not yet been determinedD 1 5 X X. We prospectively evaluated the use of the anti-TNFa monoclonal antibody etanercept (ET) as second-line treatment in children with steroid-refractory (SR) aGVHD. Twenty-five children with either malignant or nonmalignant diseases experiencing grade II-IV SR aGVHD received ET as second-line treatment. ET was administered after a median of 14 days (range, 5 to 135 days) from the onset of aGVHD. Seventeen out of 25 patients (68%) developed a complete response (CR) or partial response (PR) to ET. The oD 1 6 X Xverall response rate (CR plus PR) was 78% in patients with cutaneous SR aGVHD, 78% in those with gastrointestinal aGVHD, and 57% in those with hepatic aGVHD. On day +100 after the start of ET, 52% of the children were in CR, 16% were in PR, and the remaining 32% failed to respond. Overall survival was 76.5% in responders and 16.7% in nonresponders (P = .004). Transplantation-related mortality at 5 years was 34.1% (95% confidence interval, 18.6% to 57.1%). In our experience, ET has proven to be effective as second-line treatment in children with SR aGVHD.

Basiliximab as Treatment for Steroid-Refractory Acute Graft-versus-Host Disease in Pediatric Patients after Haploidentical Hematopoietic Stem Cell Transplantation

“…The response rate of skin was the highest, followed by that of the gut and then the liver. The survival of responders was significantly higher than that of nonresponders [18][19][20][21][22][23][24][25]. Moreover, the incidence of infection in this study was not higher than that reported in previous studies [16][17][18][19][20][21][22][23][24][25].…”

“…The survival of responders was significantly higher than that of nonresponders [18][19][20][21][22][23][24][25]. Moreover, the incidence of infection in this study was not higher than that reported in previous studies [16][17][18][19][20][21][22][23][24][25]. Thus, basiliximab is an effective second-line agent for pediatric patients with SR aGVHD after haplo-HSCT.…”

“…The overall complete response (CR) rate from the 28 published retrospective studies evaluating agents for second-line therapy of SR aGVHD was 32%, the median survival was only approximately 6 months, and no agent was clearly superior [10]. Therefore, until now the standard second-line agent for the treatment of SR aGVHD has remained unclear, and no consensus has been reached, including for pediatric patients, although previous studies have reported the use of drugs such as ruxolitinib [16,17], antithymocyte globulin (ATG) [15], etanercept [18], infliximab [19], alemtuzumab [20,21], and mycophenolate mofetil (MMF) [22] as second-line agents for SR aGVHD in pediatric patients.…”

Mesenchymal Stromal Cells in Pediatric Hematopoietic Cell Transplantation a Review and a Pilot Study in Children Treated With Decidua Stromal Cells for Acute Graft-versus-Host Disease

“…However, it is unlikely that different sources of stromal cells will be compared in prospective randomized studies for the treatment of acute GVHD. Currently, there are several promising drugs for treating acute GVHD, such as Ruxolitinib, Vedolizumab and Etanercept (110)(111)(112). However, it seems that an advantage of using MSCs is the toxicity profile.…”

Thalidomide as treatment of crohn‐like disease occurred after allogeneic hematopoietic stem cell transplantation in a pediatric patient

“…The choice to treat CD‐like colitis in our patient with Thali was based on its anti‐inflammatory and anti‐angiogenetic properties, playing a potential role in the control of CD, with lower expected immunosuppressive effect than that of anti‐TNF‐α drugs, that are associated with high risk of serious infections, especially in a patient with a delayed immune reconstitution because of the several immunosuppressive therapies received for transplant‐related immunological complication. Furthermore, after an allogeneic HSCT, the use of anti‐TNF‐α drugs is mainly reported during the acute phase of GvHD, 31,32 while, at the time of CD, our patient was in a chronic phase.…”