Bone Marrow Transplantation (2018) 53:315–325
Pentostatin therapy for steroid-refractory acute graft versus host
disease: identifying those who may beneﬁt
Brittany Knick Ragon
Rohtesh S. Mehta
Alison M. Gulbis
Rima M. Saliba
Uday R. Popat
Amanda L. Olson
Chitra M. Hosing
Muzaffar H. Qazilbash
Elizabeth J. Shpall
Richard E. Champlin
Amin M. Alousi
Received: 11 July 2017 / Revised: 20 September 2017 / Accepted: 12 October 2017 / Published online: 21 December 2017
© Macmillan Publishers Limited, part of Springer Nature 2018
We report outcomes of 60 patients with steroid-refractory (SR)-aGVHD treated with pentostatin. Almost half (47%) of patients
had grade 4 GVHD—22% had stage 3–4 liver GVHD and 51% had stage 3–4 lower gastrointestinal tract (LGI) GVHD. Patients
received a median of 3 courses (range, 1–9) of pentostatin. Day 28 overall response rate (ORR) was 33% (n = 20) (complete
response 18% (n = 11), partial response 15% (n = 9)). Non-relapse mortality was 72% (95% conﬁdence interval (CI) 61–84%)
and overall survival (OS) was 21% (95% CI 12–32%) at 18 months. On univariate analysis, age >60 years (HR 1.9, 95% CI
1.01–3.7, p = 0.045) and presence of liver GVHD (HR 1.9, 95% CI 1.9, 95% CI 1.5–3.3, p = 0.03) were signiﬁcant predictors of
poor OS while patients with LGI GVHD had superior OS than those without (HR 0.4, 95% CI 0.2–0.8, p = 0.01). On stratiﬁed
analysis, patients <60 years with isolated LGI GVHD had the best outcomes with an ORR of 48% and OS of 42% at 18 months.
Among older patients, OS was 14% in those with isolated LGI aGVHD and 0% in others. Pentostatin remains a viable treatment
option for SR-aGVHD, especially in patients 60 years or younger with isolated LGI involvement.
The most common and serious complication of allogeneic
hematopoietic stem cell transplant (HSCT) is acute graft vs.
host disease (aGVHD). Typically manifesting within the
ﬁrst 100 days following HSCT, multiple organs can be
affected including the skin, gastrointestinal tract, and/or
liver. Systemic steroids such as prednisone or methyl-
prednisolone at a dose of 1–2 mg/kg ideal body weight are
offered as initial therapy for patients with grades II-IV
aGVHD . However, only approximately one-third to half
of these patients will respond to initial steroid therapy
depending on the grade and organs involved [2–6]. Roughly
half of the patients who do not respond to initial steroid
therapy respond to second-line therapy but their mortality
rates approximate 70% .
For patients with steroid-refractory (SR) aGVHD, var-
ious additional immunosuppressive medications have been
tried with no therapy of proven superiority over others .
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 [7–11]. However, previous reports on the role of
pentostatin in SR-aGVHD have been limited by short term
follow-up and small sample sizes [10, 12–15].
Although patients with SR-aGVHD generally have dis-
mal outcomes, long-term survival does occur in select cases.
In this study, we sought to determine the factors associated
with improved responses, early mortality and long-term
survival after pentostatin use in patients with SR-aGVHD.
All patients who received pentostatin for the treatment of
SR-aGVHD from January 2006 to December 2014 at M.D.
Brittany Knick Ragon and Rohtesh S. Mehta contributed equally to
* Rohtesh S. Mehta
The University of Texas MD Anderson Cancer Center,
Houston, TX, USA
Electronic supplementary material The online version of this article
(https://doi.org/10.1038/s41409-017-0034-z) contains supplementary
material, which is available to authorized users.