Limited benefit of pentostatin salvage therapy for steroid‐refractory grade III‐IV acute graft‐versus‐host disease

Abstract

Corticosteroid-refractory (SR) acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Multiple agents have been evaluated in this setting, but the benefit of pentostatin has not been described well. We report a single-center experience of pentostatin salvage therapy for SR aGVHD. Fifteen patients received pentostatin for SR aGVHD from March 2005 till March 2010 after failure to respond to methylprednisolone ≥ 2 mg/kg/d for at least seven d. All patients had grade III-IV aGVHD prior to pentostatin therapy. Thirteen (87%), 10 (67%), and six (40%) patients had gastrointestinal (GI), skin, and liver involvement of aGVHD, respectively. Pentostatin was given at a median of 33 d after steroid therapy initiation. The dose of pentostatin was 1.4 mg/m(2) daily for three d, repeated every two wk. Eight (53%) patients also received additional therapies. Complete responses were noted in two patients (both in skin). However, one patient relapsed and did not respond to additional salvage treatment. Partial responses were seen in three patients. Fourteen died of GVHD-related causes. This study suggested that pentostatin is of limited benefit in the treatment for SR grade III-IV aGVHD.

Acute graft-versus-host disease: a bench-to-bedside update

“…Although used clinically, agents such as ATG and pentostatin have a very low durable complete response rate (20% or less). 121,122 Other immunosuppressants available include anti-IL-2 receptor-, anti-IL6 receptor-, anti-CD20-, and anti-CD52-targeted therapies. There is some data in support of extracorporeal photopheresis 123 and infusion of mesenchymal stromal cells (MSCs) 124 in refractory aGVHD.…”

Third party, umbilical cord blood derived regulatory T-cells for prevention of graft versus host disease in allogeneic hematopoietic stem cell transplantation: feasibility, safety and immune reconstitution

“…4 who developed steroid refractory grade 4 skin only GVHD at Day +60 requiring photopheresis and oral Ruxolitnib then underwent complete resolution and at 20 months post-transplant, demonstrates no evidence of GVHD with no need for continued immune suppression and remains free of his high risk leukemia. This is notable considering that patients with steroid refractory grade 4 skin GVHD have been reported to have high treatment related mortality [ 12 ] Again, larger cohort of patients will allow for valuable insights into the immune reconstitution and may unravel novel mechanisms of GVHD pathogenesis and resolution.…”

Pentostatin therapy for steroid-refractory acute graft versus host disease: identifying those who may benefit

“…These studies vary remarkably not only in the patient population, but also in terms of the dose and the number of pentostatin cycles used, additional therapies for GVHD, continuation of steroids, definition of SR-aGVHD and the assessment of response. For instance, two studies that reported a CR rate of 64-70% assessed "best response" [10,12], while other studies that assessed either day 28 response or durable response lasting 4 weeks reported CR of 13-33% and PR of 13-17% [13][14][15]. Nevertheless, one common denominator across all studies was an extremely poor prognosis of these patients with a median survival of less than 3 months.…”

“…Pentostatin, a potent adenosine deaminase (ADA) inhibitor has also been studied for GVHD prevention, therapy of newly diagnosed aGVHD, and SR-acute, and chronic GVHD [7][8][9][10][11]. However, previous reports on the role of pentostatin in SR-aGVHD have been limited by short term follow-up and small sample sizes [10,[12][13][14][15].…”