Major complication of allogeneic HSCT.
Triggered by immunocompetent donor cells.
Incidence 30-50% in sibling and up to 80% in MUD transplants
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
0.0
0
Developent of Acute GVHD
50 100
Time (days)
150
PBSC
BM
200

Acute GVHD: rash, GI, liver Chronic GVHD: skin, eyes, mouth, GI liver, musculoskeletal, lungs, GU
Alloreactivity
Immunodeficiency
Autoimmunity
- Classic acute - Late acute
- Chronic overlap
- Classic chronic
Day 0 50 100 180 1 y
Activity
(inflammation) i n j u r y r e p a i r
2 y 3 y 5 y
Damage
(fibrosis)

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

ATG
Extracorporeal photopheresis
Rituximab
Second Line
Therapy
For AGVHD
Sirolimus
CD5
Immunotoxins
Mycophenolate
Mofetil
Etanercept
Anti-TNF

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

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

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.

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.

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