Reviewer's report 
 Colon biopsies for evaluation of Acute Graft-Versus-Host Disease (A-GVHD) in allogeneic Title: 
bone marrow transplant patients. 
Authors: 
Dr Vinod Shidham ( vshidham@mcw.edu )
Chung-Che Chang ( jcchang@mcw.edu )
Ganesh Shidham ( gshidham@hotmail.com )
Farrukh Ghazala ( meh407@aol.com )
Paul Lindholm ( p-lindholm@northwestern.edu )
Bal Kampalath ( bkampala@mcw.edu )
Varghese George ( vgeorge@uab.edu )
Richard Komorowski ( rkomor@mcw.edu )
 1  11 Feb 2003 Version: Date: 
 Lisbet Sviland Reviewer: 
 A paper of limited interest Level of interest: 
 Unable to decide on acceptance or rejection until the authors have Advice on publication: 
responded to the compulsory revisions 
Discretionary revisions: 
1. In the introduction the authors state that: "The incidence of intestinal A-GVHD after allogeneic 
BMT ranges from 30% to 60% and may be associated with or without clinical signs of skin and liver 
involvement". This is not entirely correct; the incidence of A-GVHD after allogeneic BMT ranges from 30% to 60% with the skin as the most commonly affected organ. 2.Under methods when the authors describe the negative control groups they state that "the 
histopathology was negative for diagnostic pathology..." Were these reported as normal? 
3.I would like a comment on the design of the study. Was this a prospective or a retrospective study using archival biopsies? 
4. Two negative control groups were included in the study and as the authors say it would have been 
desirable to have a control group from post BMT patients without GVHD. They state this was 
impractical due to "obvious ethical limitations". Other similar studies have managed to include autologous BMT recipients as a control group. Was this a possibility? The repopulation of lymphoid cells in the gut will be different in a BMT patient group (see below). 
Compulsory revision: 
1.I would like some more clinical information: - What kind of transplant did group A receive? Was it all bone marrow or did the group include 
patients who received peripheral stem cells or cord blood transplants? 
- There is no mention of what kind of conditioning the patients received. This is important in the differential diagnosis of A-GVHD in the gut. Although as the authors state most of the pathology caused by the conditioning regimen will have disappeared by day 21 it should be included in the 
clinical details. 
- What kind of GVHD prophylaxis did the patients receive? - Were the biopsies taken before any treatment for their GVHD was commenced? 
2. It is important to exclude CMV infection as histological features of CMV can be identical to those 
seen in A-GVHD. There is no mention in the paper how CMV infection was excluded. Serology for 
CMV is unreliable in the post-BMT setting. For that matter CMV may occur together with GVHD. Did 
they do immunohistochemistry for CMV on tissue sections and if not why not? 
3. The authors state that plasme cells were more frequent in the negative control groups. They have 
in this context not discussed the difference in repopulation of lymphoid cells which occurs following a 
transplant. The control groups they have used are therefore not appropriate and the lack of a 
"chronic inflammatory response" would be expected in patients post BMT. They would have to include allogeneic BMT recipients with no GVHD or autologous transplant recipients to comment on this finding. 
Competing interests: 
None declared. 
Reviewer's report 
 Colon biopsies for evaluation of Acute Graft-Versus-Host Disease (A-GVHD) in allogeneic Title: 
bone marrow transplant patients. 
Authors: 
Dr Vinod Shidham ( vshidham@mcw.edu )
Chung-Che Chang ( jcchang@mcw.edu )
Ganesh Shidham ( gshidham@hotmail.com )
Farrukh Ghazala ( meh407@aol.com )
Paul Lindholm ( p-lindholm@northwestern.edu )
Bal Kampalath ( bkampala@mcw.edu )
Varghese George ( vgeorge@uab.edu )
Richard Komorowski ( rkomor@mcw.edu )
 1  11 Feb 2003 Version: Date: 
 Lisbet Sviland Reviewer: 
 A paper of limited interest Level of interest: 
 Unable to decide on acceptance or rejection until the authors have Advice on publication: 
responded to the compulsory revisions 
Discretionary revisions: 
1. In the introduction the authors state that: "The incidence of intestinal A-GVHD after allogeneic 
BMT ranges from 30% to 60% and may be associated with or without clinical signs of skin and liver 
involvement". This is not entirely correct; the incidence of A-GVHD after allogeneic BMT ranges from 30% to 60% with the skin as the most commonly affected organ. 2.Under methods when the authors describe the negative control groups they state that "the 
histopathology was negative for diagnostic pathology..." Were these reported as normal? 
3.I would like a comment on the design of the study. Was this a prospective or a retrospective study using archival biopsies? 
4. Two negative control groups were included in the study and as the authors say it would have been 
desirable to have a control group from post BMT patients without GVHD. They state this was 
impractical due to "obvious ethical limitations". Other similar studies have managed to include autologous BMT recipients as a control group. Was this a possibility? The repopulation of lymphoid cells in the gut will be different in a BMT patient group (see below). 
Compulsory revision: 
1.I would like some more clinical information: - What kind of transplant did group A receive? Was it all bone marrow or did the group include 
patients who received peripheral stem cells or cord blood transplants? 
- There is no mention of what kind of conditioning the patients received. This is important in the differential diagnosis of A-GVHD in the gut. Although as the authors state most of the pathology caused by the conditioning regimen will have disappeared by day 21 it should be included in the 
clinical details. 
- What kind of GVHD prophylaxis did the patients receive? - Were the biopsies taken before any treatment for their GVHD was commenced? 
2. It is important to exclude CMV infection as histological features of CMV can be identical to those 
seen in A-GVHD. There is no mention in the paper how CMV infection was excluded. Serology for 
CMV is unreliable in the post-BMT setting. For that matter CMV may occur together with GVHD. Did 
they do immunohistochemistry for CMV on tissue sections and if not why not? 
3. The authors state that plasme cells were more frequent in the negative control groups. They have 
in this context not discussed the difference in repopulation of lymphoid cells which occurs following a 
transplant. The control groups they have used are therefore not appropriate and the lack of a 
"chronic inflammatory response" would be expected in patients post BMT. They would have to include allogeneic BMT recipients with no GVHD or autologous transplant recipients to comment on this finding. 
Competing interests: 
None declared. 
Please review this paper.
user
Reviewer's report 
 Colon biopsies for evaluation of Acute Graft-Versus-Host Disease (A-GVHD) in allogeneic Title: 
bone marrow transplant patients. 
Authors: 
Dr Vinod Shidham ( vshidham@mcw.edu )
Chung-Che Chang ( jcchang@mcw.edu )
Ganesh Shidham ( gshidham@hotmail.com )
Farrukh Ghazala ( meh407@aol.com )
Paul Lindholm ( p-lindholm@northwestern.edu )
Bal Kampalath ( bkampala@mcw.edu )
Varghese George ( vgeorge@uab.edu )
Richard Komorowski ( rkomor@mcw.edu )
 1  11 Feb 2003 Version: Date: 
 Lisbet Sviland Reviewer: 
 A paper of limited interest Level of interest: 
 Unable to decide on acceptance or rejection until the authors have Advice on publication: 
responded to the compulsory revisions 
Discretionary revisions: 
1. In the introduction the authors state that: "The incidence of intestinal A-GVHD after allogeneic 
BMT ranges from 30% to 60% and may be associated with or without clinical signs of skin and liver 
involvement". This is not entirely correct; the incidence of A-GVHD after allogeneic BMT ranges from 30% to 60% with the skin as the most commonly affected organ. 2.Under methods when the authors describe the negative control groups they state that "the 
histopathology was negative for diagnostic pathology..." Were these reported as normal? 
3.I would like a comment on the design of the study. Was this a prospective or a retrospective study using archival biopsies? 
4. Two negative control groups were included in the study and as the authors say it would have been 
desirable to have a control group from post BMT patients without GVHD. They state this was 
impractical due to "obvious ethical limitations". Other similar studies have managed to include autologous BMT recipients as a control group. Was this a possibility? The repopulation of lymphoid cells in the gut will be different in a BMT patient group (see below). 
Compulsory revision: 
1.I would like some more clinical information: - What kind of transplant did group A receive? Was it all bone marrow or did the group include 
patients who received peripheral stem cells or cord blood transplants? 
- There is no mention of what kind of conditioning the patients received. This is important in the differential diagnosis of A-GVHD in the gut. Although as the authors state most of the pathology caused by the conditioning regimen will have disappeared by day 21 it should be included in the 
clinical details. 
- What kind of GVHD prophylaxis did the patients receive? - Were the biopsies taken before any treatment for their GVHD was commenced? 
2. It is important to exclude CMV infection as histological features of CMV can be identical to those 
seen in A-GVHD. There is no mention in the paper how CMV infection was excluded. Serology for 
CMV is unreliable in the post-BMT setting. For that matter CMV may occur together with GVHD. Did 
they do immunohistochemistry for CMV on tissue sections and if not why not? 
3. The authors state that plasme cells were more frequent in the negative control groups. They have 
in this context not discussed the difference in repopulation of lymphoid cells which occurs following a 
transplant. The control groups they have used are therefore not appropriate and the lack of a 
"chronic inflammatory response" would be expected in patients post BMT. They would have to include allogeneic BMT recipients with no GVHD or autologous transplant recipients to comment on this finding. 
Competing interests: 
None declared. 
assistant