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Anti-T cell globulin reduces incidence of acute and chronic GVHD in transplant patients

Lancet

Giving patients undergoing blood stem cell transplantation from an unrelated donor, standard graft-versus-host-disease (GVHD) prophylaxis in combination with anti-T-cell globulin (ATG), prevents both acute and chronic GVHD compared with standard treatment alone, without compromising survival or increasing relapse, notes an Article published Online First and in the September edition of The Lancet Oncology.

GVHD is a common complication after haematopoietic cell transplantation (HCT)--transplantation of blood stem cells from the bone marrow or peripheral blood--from unrelated donors. In this disease, the immune system or T-cells from the donor attack the body of the recipient. Up to 60% of recipients develop GVHD. Previous studies have suggested that ATGs--antibodies that eliminate T-cells in vivo--might prevent GVHD.

To investigate further, Jürgen Finke from Universitätsklinikum Freiburg in Germany and colleagues did a phase 3 trial in patients undergoing HCT from an unrelated donor to compare standard GVHD prophylaxis (cyclosporine and methotrexate) with anti-Jurkat ATG-Fresenius (ATG-F).

In total, 201 adult patients with haematological cancers undergoing HCT from an unrelated donor were recruited from 31 treatment centres in Europe and Israel between May 2003 and February 2007. Patients were randomly assigned to prophylaxis with cyclosporine and methotrexate with or without additional ATG-F. The researchers assessed them for early treatment failure, defined as acute GVHD (aGVHD)* grade III-IV or death within 100 days of transplantation, and incidence of chronic GVHD (cGVHD) **.

Within 100 days of transplantation, 22 patients (21·4%) in the ATG-F group had aGVHD grade III-IV or had died, compared with 33 patients (33·7%) in the standard treatment group--no significant benefit with ATG-F was shown within 100 days.

However, overall, findings showed that the incidence of aGVHD grade III-IV was reduced in the ATG-F treatment group--11·7% vs 24·5% in the standard treatment group. Nine patients died of aGVHD in the standard treatment group compared with only one patient in the ATG-F group.

Importantly, ATG-F had a significant effect in reducing cGVHD--the 2-year cumulative incidence of cGVHD and extensive cGVHD in the ATG-F group was 30·8% and 12.2%, respectively, compared with 58·8% and 42·6%, respectively, in the standard treatment group.

The authors point out that despite the advanced disease status of many patients, there were no increases in relapse, non-relapse mortality, overall survival, or deaths from infection in patients treated with ATG-F compared with controls.

They comment***: "This is the first randomised clinical trial to show that ATG-F can reduce severe acute and clinically-relevant chronic GVHD without compromising disease-free survival or overall survival...The use of ATG-F is safe for patients who are going to receive transplantation from matched unrelated donors."

In an accompanying Reflection and Reaction, Francesco Frassoni from Ospedale San Martino in Italy comments***: "ATG looks like remaining an essential ingredient of HCT. For tomorrow's patient knowing that they can receive a transplant with a lower probability of developing both acute and chronic GVHD, without increasing the risk of recurrence of their disease, is reassuring."

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Professor Jürgen Finke, Universitätsklinikum Freiburg, Germany.

T) +49 761 270 3408 E) juergen.finke@uniklinik-freiburg.de

Dr Francesco Frassoni, Centro Cellule Staminali e Terapia Cellulare, Ospedale San Martino, Genova, Italy. E) Francesco.frassoni@hsanmartino.it

Notes to Editors:

*Acute graft-versus-host-disease (aGVHD) occurs within 100 days of transplantation and involves the donor immune cells attacking the host's skin, intestines and liver, and is deadly in up to 40% of cases.

**Chronic-graft-versus-host-disease (cGVHD) is the most common disease and cause of death in long-term survivors and includes problems such as dryness of the eyes and mouth, skin rashes, stiff joints, and infections due to a weakened immune system.

***Independent quote from authors.

http://www.eurekalert.org/jrnls/lance/ONC_SEP_A_Finke+Frassoni.pdf

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