Regional intra-arterial steroid treatment in 120 patients with steroid-resistant or -dependent GvHD

Abstract

GvHD results in death in the majority of steroid-resistant patients. This report assesses the safety and efficacy of two regional intra-arterial steroid (IAS) treatment protocols in the largest published cohort of patients with resistant/dependent hepatic and/or gastrointestinal GvHD, as well as identification of predictors of response to IAS and survival. One hundred and twenty patients with hepatic, gastrointestinal GvHD or both were given IAS. Gastrointestinal initial response (IR) and complete response (CR) were documented in 67.9% and 47.6%, respectively, whereas hepatic IR/CR in 54.9% and 33.3%, respectively. The predictors of gastrointestinal CR were lower peak GvHD and steroid-dependent (SD) GvHD. The predictors for hepatic CR were male patient, reduced intensity conditioning and SD GvHD. Twenty-six of the 120 patients (21.6%) are currently alive (median follow-up for the survivors 91.5 months). The 12 months' overall survival is 30% with no treatment-associated deaths. Predictors of 12 months' survival were as follows: first transplant, age<20 years, non-TBI regimen and GvHD CR. Shorter time to gastrointestinal IR but not time to hepatic IR was associated with improved 12 months' survival. IAS appears to be safe and effective. Gastrointestinal treatment is more effective than hepatic treatment. In our study, we conclude our current recommendations for IAS treatment.

Ruxolitinib as a Novel Therapeutic Option for Poor Prognosis T-LBL Pediatric Patients

“…To date, aberrant regulation of the JAK1/2-STAT6 pathway has been identified in different pathological conditions [9] and activated STAT6 has been found in patient samples isolated from Hodgkin lymphomas [10,11], cutaneous T cell lymphomas [12], adult T cell leukemia and B-lymphomas [13,14]. In this article we functionally validated JAK2 Y1007-1008 as a new therapeutic target to reverse therapy resistance by in vitro treatment with ruxolitinib, an already FDA approved JAK1/2 inhibitor [15,16] that is currently also being evaluated for the treatment of B-ALL (NCT02723994) [17], alone or in combination with dexamethasone, in cell lines and in one T-LBL pediatric primary sample. Moreover, our findings also revealed that in these cells STAT6 controls the transcriptional activity of the glucocorticoid receptor (GR) through the binding of GR itself and the inhibition of its activity, which contributes to increasing glucocorticoid (GC) resistance.…”

Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graft-versus-host disease as a second-line therapy: a multicentre, randomized, controlled trial

“…The OR/CR of GI GVHD was 67.9% and 47.6%, whereas the hepatic OR/CR was 54.9% and 33.3%, respectively. However, its routine use may be limited by the complications associated with arterial catheterization, such as arterial rupture, dissection or thrombosis, temporary arterial spasm, groin haematoma or cellulitis and, rarely, renal failure [ 44 ].…”

Precision Delivery of Steroids as a Rescue Therapy for Gastrointestinal Graft-versus-Host Disease in Pediatric Stem Cell Transplant Recipients

“…Intraarterial methylprednisolone administration has shown promise as a potential salvage therapy in steroid-resistant acute GVHD in adults [ 9 , 10 , 11 ]. While one study included an unknown number of pediatric patients [ 19 ], this technique has not been reported in a pediatric cohort of patients outside selective case reports. Understanding the feasibility and efficacy of intraarterial steroid treatment for acute GVHD in children is important because this population suffers from a higher incidence of severe GVHD following SCT and is more likely to experience complications from systemic steroid administration [ 20 , 21 , 22 ].…”