Interference of Monoclonal Antibody Therapy in Transfusion: An Update
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe paper presented for review concerns and analyzed interference of monoclonal antibody therapy in pretransfusion testing. The subject matter of the article is very important because it emphasizes problems in providing safe transfusion with minimal risk as possible for patients who are on monoclonal antibody therapy. The analysis of the topics raised by the Authors has been presented in a clear and coherent manner. All items of scientific literature are up to date. The language of the work is understandable and easy to read. The manuscript is generally well written and clear.
Specific points:
11. Line 139: “and use of Darasorb for pre-analytic depletion of anti-CD38 from patient plasma”
What about DaraEx or DaraEx-plus – treated RBC? Maybe you can add your opinion about it too.
22. Line 229-230: “Phenotyping (if no transfusion/pregnancy/transplantation 3 months before) or genotyping for Rh (CcDEe), K, JKa. JKb, Fya, Fyb, M, N, S and s”
The reference you refer to (51) does not require phenotyping and genotyping to be done for M and N.
Genotype should also be performed if there were recent transfusions or DAT is positive.
33. Although monoclonal antibody therapy makes difficult pre-transfusion examination in transfused patients treated with MoAb, do you have information on whether it has ever been reported a case of hemolytic transfusion reaction?
I rate this paper very well in terms of content and recommend it for publication after minor additions indicated in the review.
Author Response
Specific points:
- Line 139: “and use of Darasorb for pre-analytic depletion of anti-CD38 from patient plasma”
What about DaraEx or DaraEx-plus – treated RBC? Maybe you can add your opinion about it too.
Authors have no knowledge enough to add an opinion
- Line 229-230: “Phenotyping (if no transfusion/pregnancy/transplantation 3 months before) or genotyping for Rh (CcDEe), K, JKa. JKb, Fya, Fyb, M, N, S and s”
The reference you refer to (51) does not require phenotyping and genotyping to be done for M and N.
We have deleted M and N
Genotype should also be performed if there were recent transfusions or DAT is positive.
We have added it
- Although monoclonal antibody therapy makes difficult pre-transfusion examination in transfused patients treated with MoAb, do you have information on whether it has ever been reported a case of hemolytic transfusion reaction?
No, we have not any relevant information about hemolysis related to monoclonal antibody therapy
Reviewer 2 Report
Comments and Suggestions for AuthorsThis review touches an area which is of growing importance for many types of blood banks and laboratories performing compatibility testing for blood products including red cells. The two main types of pharmaceuticals, CD38 binding and CD47 binding antibodies are the most relevant for the time being. Most of the references are timely but some recent articles are missing. On a general level the manuscript displays expertise in the subject area. However, it is obvious that the practical and scientific expertise of the authors is restricted to some methods and a large part of the review is based on literature.
The main intention of the manuscript remains slightly obscure since the authors have included guideline-type recommendations in their text in addition to reviewing the literature, which I think is not entirely justified. It would have been more logical to describe the main alternatives more thoroughly and discuss their pros and cons. I suggest that the flowchart would be deleted from the manuscript.
There are some other minor defects in the text. The Kell blood group has only been discussed in terms of K but in some populations the number of k negatives may be significant and should be taken into accouunt if the DTT denatures the Kell epitopes on a general level. Some of the references about antibody drug products under development are slightly outdated.
I have included my suggestions for alterations to the document enclosed. The suggestions include both English language and scientific content.
Comments for author File: 
Comments.pdf
The spelling and grammar of English are understandable but there are numerous small mistakes and deviations from scientific style. I am not a native English speaker so I do not assume that my review in this respect would be comprehensive. In addition to the language there are minor flaws in the format of the writing; e.g. blood Banks vs Blood Banks vs blood banks/ CD38 vs CD 38 etc. A thorough proofreading preferably by a native English speaker would make the article better.
Author Response
Thanks a lot for the comments. We have decided to maintain the workflow because in our opinion, it summarises all the knowledge about transfusion management of patients receiving monoclonal antibody therapy
Reviewer 3 Report
Comments and Suggestions for AuthorsThe review by Alcaina and Cantó provides a comprehensive summary of evidence on challenges for transfusion specialists derived from administering monoclonal antibody (MoAb) therapy for hematologic malignancies. Some of these new therapies have been found to interfere with pre-transfusion testing and sometimes have the potential to cause hemolytic anaemia. The authors outline various methods to overcome these interferences, such as treating reagent RBCs with enzymes or reducing agents, allogeneic RBC adsorptions, and drug-specific neutralization assays. The review offers an overview of the currently available MoAb, highlighting its new challenges for blood banks and emphasizing the importance of effective communication between laboratory and clinical settings. Only a few suggestions are made.
· Pag. 1 line 43: please use the acronym IAT
· Pag. 3 line 99: RBC instead of RBS
· Pag. 7 Figure 1. Workflow to address the interferences of MoAbs in pre-transfusion testing: I suggest explicitly stating the competence involved, i.e., transfusion service or clinicians.
Comments on the Quality of English Languageminor revision required
Author Response
Pag. 1 line 43: please use the acronym IAT
Changed
- Pag. 3 line 99: RBC instead of RBS
Changed
