scholarly journals Limited Benefit of Pentostatin Salvage Therapy for Steroid Refractory Acute Graft Versus Host Disease

2012 ◽  
Vol 18 (2) ◽  
pp. S372
Author(s):  
N. Alam ◽  
A. Viswabandya ◽  
J. How ◽  
V. Gupta ◽  
D. Kim ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Salvage Therapy ◽  
Host Disease ◽  
Graft Versus Host ◽  
Steroid Refractory ◽  
Acute Graft

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

2013 ◽  
Vol 27 (6) ◽  
pp. 930-937 ◽  
Author(s):  
Naheed Alam ◽  
Eshetu G. Atenafu ◽  
Garwin Tse ◽  
Auro Viswabandya ◽  
Vikas Gupta ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Salvage Therapy ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Iii ◽  
Steroid Refractory ◽  
Acute Graft

Pentostatin for First-Line Salvage Therapy of Steroid-Refractory Intestinal Acute Graft-Versus-Host Disease; a Dual Center Retrospective Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1274-1274
Author(s):  
Stefan A. Klein ◽  
Thomas Schmitt ◽  
Gesine Bug ◽  
Thomas Luft ◽  
Sabine Mousset ◽  
...  
Keyword(s):  
Stem Cells ◽  
Graft Versus Host Disease ◽  
Salvage Therapy ◽  
Conditioning Regimen ◽  
Gi Tract ◽  
First Line ◽  
Host Disease ◽  
Graft Versus Host ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Abstract 1274 Acute graft-versus-host disease (aGvHD) of the gastrointestinal (GI) tract remains a major complication after allogeneic stem cell transplantation. The outcome of patients who fail first-line therapy with steroids is poor. There is no standard therapy for steroid-refractory aGvHD. A promising strategy is the use of pentostatin, an inhibitor of adenosine deaminase. The capacity of this purine analogue to inhibit proliferation and to induce apoptosis of T-cells in combination with its mild toxicity resulted in the approach to use pentostatin in steroid-refractory aGvHD. Here we report on our experience with pentostatin in steroid-refractory aGvHD at the universities of Frankfurt (F) and Heidelberg (H). Patients: From 2000 to 2009 (F) and from 2005 to 2009 (H) a total number of 72 (F: n=39; H: n=33) consecutive patients who had undergone first-line salvage treatment of histologically proven severe steroid-refractory aGvHD of the GI-tract with pentostatin were retrospectively analyzed. Steroid-refractory aGvHD was defined as progression or no improvement of diarrhea despite a treatment with prednisolone (≥2mg/kg/d) for ≥ 3 days. In steroid-refractory aGvHD pentostatin was infused at a dose of 1mg/m2 for 3 consecutive days. Patients received 1–4 cycles. Response after therapy with pentostatin was classified as complete (CR, no ongoing symptoms of GvHD), very good partial (VGPR, residual symptoms only) or no response (NR). 31 females and 41 males with a median age of 48 (range: 20–68) years were included. The underlying diseases were AML (n=43), ALL (n=10), CML (n=1), lymphoma (n=7), MDS (n=6), and multiple myeloma (n=5). The conditioning regimen was myeloablative in 25 patients and reduced intensity in 47 patients. Patients were transplanted with peripheral blood stem cells (except one bone marrow transplantation) from matched siblings (n=26), matched unrelated (n=27) or mismatched donors (n=19). All patients suffered from severe steroid-refractory intestinal aGvHD overall grade III (n=39) or IV (n=33). Results: 39 patients (54%) responded to pentostatin. 30 patients (42%) achieved CR, 9 patients (12%) VGPR. Clinical improvement occurred within a median of 13 (range: 5–58) days after the first infusion of pentostatin. 33 patients (46%) did not respond. After a median follow up of 27 (range 10 to 108) months 23 patients (32%) are alive. 49 patients (68%) died (53% therapy related, 15% due to relapse of the malignant disease). 59% of the 39 responding patients versus 0% of the non-responders survived. 10 patients without response to pentostatin received further salvage therapies including alemtuzumab, infliximab, rituximab, tacrolimus, etanercept or mesenchymal stem cells (MSC). All these patients died without response. 26 patients (36%) achieved CR or VGPR after one cycle of pentostatin. 24 patients without CR or VGPR after one cycle were treated with 1–3 further cycles. The probability of survival was significantly higher for patients who responded after one cycle in comparison with patients without response and further pentostatin treatment (73% versus 13%, p<0.01). Thus, further immunosuppressive therapy beyond one cycle of pentostatin has almost no positive impact on survival. Except one patient who died 4 years after pentostatin due to relapse of lymphoma all one-year-survivors stayed alive. Conclusions: In the critical clinical situation of severe steroid-refractory intestinal aGvHD pentostatin conferred encouraging rates of response and overall survival. In comparison with other treatment options such as MSC or immunosuppressive monoclonal antibodies pentostatin has some favorable characteristics: Its effect is sustainable; the majority of responding patients survived. Costs for pentostatin are relatively low and toxicity is moderate. However, despite therapy with pentostatin mortality in steroid-refractory aGvHD is still unacceptably high. Since response rates and survival after other therapies are even less convincing we suggest using pentostatin as salvage therapy in severe steroid-refractory intestinal aGvHD. Disclosures: Klein: Hospira: Honoraria.

Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1224-1226 ◽  
Author(s):  
Vincent T. Ho ◽  
David Zahrieh ◽  
Ephraim Hochberg ◽  
Eileen Micale ◽  
Jesse Levin ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Phase 1 ◽  
Interleukin 2 ◽  
Maximum Tolerated Dose ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Denileukin Diftitox ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Denileukin diftitox (Ontak), a recombinant protein composed of human interleukin 2 (IL-2) fused to diphtheria toxin, has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor. We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease (GVHD). Seven patients received 9 μg/kg intravenously on days 1 and 15; 18 received 9 μg/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 μg/kg intravenously on days 1 to 5 and 15 to 19. Hepatic transaminase elevation was the dose-limiting toxicity (DLT), and dose level 2 was the maximum tolerated dose (MTD). Overall, 71% of patients responded with complete resolution (12 of 24; 50%) or partial resolution (5 of 24; 21%) of GVHD. Eight of 24 patients (33%) are alive at 6.3 to 24.6 months (median, 7.2 months). Denileukin diftitox is tolerable and has promising activity in steroid-refractory acute GVHD. (Blood. 2004;104:1224-1226)

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