Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD

Abstract

Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n ¼ 10), III (n ¼ 7) or IV (n ¼ 6)). The median duration of ECP was 7 months (1-33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day þ 90 from ECP) (P ¼ 0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P ¼ 0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P ¼ 0.1). A trend for improved survival was seen in grade III-IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease.

Pentostatin for treatment of steroid-refractory acute GVHD: a retrospective single-center analysis

“…28 Extracorporal photochemotherapy has been reported to induce CRs in up to 61 and 40% of patients with GI aGVHD, respectively, depending on GVHD grade. 29,30 The use of MSCs has been of emerging interest in the treatment of aGVHD because of their immunoregulatory potential. Le Blanc et al 31 achieved CR rates of 55% (30/55) in a phase II study.…”

State-of-the-art acute and chronic GVHD treatment

“…Transplant-related mortality was only 14 % in patients treated with ECP while 73 % in patients who were not [104]. Other retrospective studies have also shown benefit of ECP in treatment of aGVHD [105]. ECP is safe, without any increase in rate of infections, secondary malignancies or mortality [106].…”

Extracorporeal photochemotherapy as second- or first-line therapy of acute GVHD?

“…A clinical benefit has first been suggested in patients with chronic GVHD, and several prospective or retrospective studies reported promising results in patients with steroid refractory acute GVHD (aGVHD). 1,2 The theoretical advantages of ECP are no increased risk of infection, no adverse events such as metabolic or organic impairment and potential preservation of the GVL effect. 2 Moreover, as its immunomodulatory effects do not rely on the destruction or inactivation of cells but rather on the generation of active immune cells, these effects can be sustained and no severe flare-up of GVHD has been reported.…”

“…1,2 The theoretical advantages of ECP are no increased risk of infection, no adverse events such as metabolic or organic impairment and potential preservation of the GVL effect. 2 Moreover, as its immunomodulatory effects do not rely on the destruction or inactivation of cells but rather on the generation of active immune cells, these effects can be sustained and no severe flare-up of GVHD has been reported. 1 In a recent retrospective study, Calore et al 3 have compared the outcome of children with aGVHD depending on whether they had been treated with ECP or not.…”

“…However, this and other studies suggest that the use of ECP could lead to the strange situation in which patients who do not respond to the consensual first-line therapy with steroids have a better outcome compared with those who do. 2,3 The ideal treatment of aGVHD must combine a potent anti-GVH effect with no impairment of anti-infectious and anti-leukemic immunity. The apparent insolvability of this challenging equation explains why, until now, no first-line combination therapy (especially including anti-CD25 monoclonal antibodies, a recognized useful second-line therapy) has done better than steroids alone to improve the OS of patients who developed acute GVH after allogeneic BMT for malignant disease.…”