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

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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.

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

GVHD Syndrome After

Allotransplant

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

Options for second line therapy for

GVHD

ATG

Extracorporeal photopheresis

Rituximab

Second Line

Therapy

For AGVHD

Sirolimus

CD5

Immunotoxins

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

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