Transcript A single-centre experience of the efficacy of ECP in the

A single centre study of the
efficacy of extracorporeal
photopheresis in Acute Graft
Versus Host Disease
Lynne Watson
Nottingham University
Hospital NHS Trust
Acute Graft-Versus-Host Disease
Major complication
of allogeneic HSCT.
Developent of Acute GVHD
1.0
.9
.8
% Acute GVHD
Triggered by
immunocompetent
donor cells.
.7
.6
PBSC
.5
.4
.3
BM
.2
Incidence 30-50% in
sibling and up to 80%
in MUD transplants
.1
0.0
0
50
100
Time (days)
150
200
GVHD Syndrome After
Allotransplant
Acute GVHD: rash, GI, liver
Chronic GVHD: skin, eyes, mouth, GI
liver, musculoskeletal, lungs, GU
Alloreactivity
Autoimmunity
Immunodeficiency
- Classic acute
- Late acute
- Chronic overlap
Day
0
50
Activity
(inflammation)
100
injury
- Classic chronic
180
repair
1y
2y
3y
Damage
(fibrosis)
5y
Treatment of severe acute GvHD
High dose steroids (2mg/kg/day) is standard approach for
the treatment of grade II-IV acute GvHD treatment
~ 40-50% of patients with grade II-IV disease are steroid
responsive
Higher response rates in grade II compared to grade III/IV
disease and in patients with one organ involved compared
to 2 or 3.
Responses are worse in patients receiving MUD
transplants.
Overall CR is only seen in 25-40% of patients
Options for second line therapy for
GVHD
ATG
Extracorporeal
photopheresis
Rituximab
Second Line
Therapy
For AGVHD
CD5
Immunotoxins
Sirolimus
Mycophenolate
Mofetil
Etanercept
Anti-TNF
Extracorporeal Photopheresis (ECP)
ECP is based upon the re-infusion of apoptotic autologous
blood mononuclear cells which have been treated
extracorporeally with the DNA intercalating agent 8 –
methoxypsoralen and then irradiated with PUVA
ECP has demonstrated efficacy in selected T cell diseases
including chronic GvHD and cutaneous T cell lymphoma
The experience of ECP in Acute GVHD is much less than
that with chronic. Greinix et al (2006) reported a phase
II study of 59 patients treated with ECP for steroid
refractory acute GvHD using an intensive schedule of
a cycle of therapy ( 2 consecutive daily treatments)
weekly for 8 weeks
ECP Schedule for acute GVHD
We established an ECP programme for acute
and chronic GVHD in Nottingham in 2006 using
the Therakos XTS system
Previously we had used ATG in this setting but
with a poor response and a high incidence of
infectious complications
18 consecutive patients with steroid-refractory
acute GVHD have been treated with twice
weekly ECP at weekly intervals for a planned 8
week course (Greinix schedule)
In 2009 we started using the new Cellex system
for suitable patients
ECP for Acute GVHD
18 consecutive patients with steroid-refractory acute
GVHD post BMT (n=11) or DLI therapy (n=7)
GVHD was grade II in 2, grade III in 6 and grade IV in 10
patients.
66% of patients had 2 or 3 organ involvement
Patients had been on steroids (2mg/kg) for a median of
14 days (7-88 days) before starting ECP.
The aim was to achieve a rapid steroid taper in
responding patients
Results – Response at 8 weeks
Primary end point of the analysis was the
response after 8 weeks of ECP therapy.
CR was arbitrarily defined as resolution of
features of acute GvHD with a reduction of
prednisolone dose to 10mg/day or less
12/18 patients have completed 8 weeks of ECP
6 died of progressive GvHD prior to completing
their 8 weeks of allocated ECP therapy.
Overall Response to ECP
All of the 12 /18 (66%) patients who completed 8
weeks of therapy have responded.
In the 12 patients who have completed the 8 weeks
of therapy CR was achieved in 8.
4 patients achieved a partial response but remained
on higher dose of steroids than 10mg/day at 8
weeks.
Response was dependent upon severity and extent
of GvHD.
Example of Bilirubin Response
Rates to ECP
Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Wk 6 Wk 7 Wk 8
494
396
313
283
426
252
187
142
Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Wk 6 Wk 7 Wk 8
235
103
88
69
44
24
21
15
Updated Outcome on Responding Patients
Median follow-up is now 2 years.
8 patients have developed chronic GvHD and
remain on some immunosuppression. This
includes 2 patients with major relapse of liver
GVHD 4-6 months after stopping ECP. Both
patients responded to re-starting ECP therapy.
3 patients have no GvHD and are off all
immunosuppression.
1 patient who had a PR to ECP died of HHV 6
encephalitis.
Only 1 patient has had relapsed of their disease.
Summary
12/18 patients with grade II - IV steroid-refractory acute
GvHD completed their scheduled 8 weeks course of
intensive ECP
All patients responded with 8 achieving CR and 4 PR
Excellent and rapid responses were seen in patients
with isolated skin or liver GvHD . The response rate was
lower in patients with 3 organ involvement
5/7 patients who developed GVHD post DLI responded
8 patients survive >12 months post completion of ECP
and 3 patients are off all immunosuppression
2 patients have had significant relapse of liver GVHD
and both responded again to re-introduction of ECP
8 patients survive >12 months post completion of ECP