Aggressive Neuroblastoma in a Pediatric Patient with Severe Hemophilia A

Round 1

Reviewer 1 Report

While it is interesting to see the report of how hemophilia A impacts neuroblastoma treatment, it would be nice if there was a bit more generalization regarding the message of this case.  The details of the initial hemophilia presentation in the NICU do not add significantly to the case.  Additionally, the discuss of the refractory neuroblastoma requiring multiple regimens makes me wonder if there is an association between hemophilia and more severe disease from a neuroblastoma standpoint.  

Author Response

Response to Reviewer 1 comments (in blue)

 

We appreciated the reviewer’s comments to improve the manuscript. Please consider our reply to the specific questions, as displaced below:

Point 1: “While it is interesting to see the report of how hemophilia A impacts neuroblastoma treatment, it would be nice if there was a bit more generalization regarding the message of this case”. 

Response 1: We thank you your considerations. It would be interesting to give a more comprehensive insight on this subject, however, we are limited by the fact this is a case report. Thus, we stuck up to case description of hemophilia A and neuroblastoma.

 

Point 2: “The details of the initial hemophilia presentation in the NICU do not add significantly to the case”. 

Response 2: We agree with your suggestion. We revised the main text and summarized the findings.

 

Point 3: “Additionally, the discuss of the refractory neuroblastoma requiring multiple regimens makes me wonder if there is an association between hemophilia and more severe disease from a neuroblastoma standpoint”.

Response 3: The hypothesis you have raised is very interesting, however with only one case one cannot draw definitive conclusions.

 

Point 4: English language and style – moderate changes required.

Reponse 4: We revised grammar and construction. We tried to improve the original manuscript.

 

Please consider the attached file.

Author Response File: Author Response.docx

Reviewer 2 Report

Dear Authors,

Congratulations for your interesting experience and thank you for sharing it.

I have some comments/suggestions:

Abstract:

Pag. 2: children with haemophilia are, nowadays, well treated and managed in countries where factor replacement is available ... I don't think that it is correct to define haemophilia an aggressive disease. Moreover, I'd suggest to "highlight" the importance of diagnosis process.

Introduction 

Pag. 3: it could be suggested to add more informations about neuroblastoma.

Please check references 3 and 4 reported before reference 1.

Results: 

Pag. 3: why it was decided not to start with prophylaxis after the first bleeding at birth? Please explain.

Discussion:

Pag. 9 line 2: "There are very few reports": it could be suggested to add some references

Pag. 9 line 11: "is not always clear": is it an author's statement? if not, it could be suggested to add a reference.

Pag. 10 line 4: as I previously commented and clearly demonstrated by your experience, I think that "extraordinary" could be removed.

Author Response

Response to Reviewer 2 comments (in blue)

 

We appreciated the reviewer’s comments to improve the manuscript. Please consider our reply to the specific questions, as displaced below:

Point 1: 2: children with haemophilia are, nowadays, well treated and managed in countries where factor replacement is available ... I don't think that it is correct to define haemophilia an aggressive disease. Moreover, I'd suggest to "highlight" the importance of diagnosis process.

Response 1: We agree with your suggestion that hemophilia A is not an aggressive disease. We removed “aggressive” from the main text.

 

Point 2: 3: it could be suggested to add more information about neuroblastoma.

Response 2: We added some information regarding neuroblastoma (page 3, lines 6-7).

 

Point 3: Please check references 3 and 4 reported before reference 1.

Response 3: We agree they are not correct. We have already corrected them at the main text.

 

Point 4: 3: why it was decided not to start with prophylaxis after the first bleeding at birth? Please explain.

Response 4: Patient did not undergo regular prophylaxis after birth because the first hemorrhage was associated with birth trauma. It was properly managed and did not recur. After discussion with the parents, and since the child presented lack of appropriate venous accesses, it was decided to postpone regular prophylaxis. Due to word count limitations, we did not provide this information in the main text since it was not essential for the case report.

 

Point 5: 9 line 2: "There are very few reports": it could be suggested to add some references.

Response 5: We added reference 7 to the main text, which reports a case of lymphoma in a severe hemophilia B patient in pediatric age.

To our knowledge, besides lymphoma, there are no other literature reports.

 

Point 6: 9 line 11: "is not always clear": is it an author's statement? if not, it could be suggested to add a reference.

Response 6: This statement refers to our perception of clinical evaluation of these patients. It is difficult to nominate a reference for this finding.

 

Point 7: 10 line 4: as I previously commented and clearly demonstrated by your experience, I think that "extraordinary" could be removed.

Response 7: We agree with your suggestion. We removed “extraordinary” from the main text.

 

Point 8: English language and style – English language and style are fine/minor spell check required.

Response 8: We revised grammar and construction. We tried to improve the original manuscript.

 

Please consider the attached file.

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

The changes that were made are only some surface rewording.  I'm not sure they changed the paper much.  It is an interesting report of a patient unlucky enough to have two problems, but it doesn't add too much to the literature in terms of ideas that will change clinical practice.

Author Response

Response to Reviewer 1 Comments (in blue)

 

We appreciated the reviewer’s comments to improve the manuscript. Please consider our reply to the specific questions, as displaced below:

 

Point 1: The changes that were made are only some surface rewording.  I'm not sure they changed the paper much.  It is an interesting report of a patient unlucky enough to have two problems, but it doesn't add too much to the literature in terms of ideas that will change clinical practice.

 

Response 1: We agree with Reviewer 1 and we recognize that this case does not have therapeutic-changing implications in hemophilia management. However, this case report enhances how multidisciplinary close approach diminish hemophilia complications and confirms that severe hemophilia was not impeding to intensive cancer treatment, including aplasia phases with severe thrombocytopenia-therapy-related. We highlight teamwork and different institutions cooperation as essential to manage these patients.

This article might open a window towards further investigation on neoplastic diseases and hemophilia in pediatric setting, which does not exist so far.

To our knowledge, this is the first report of a child with aggressive neuroblastoma and severe hemophilia, in the literature, which prompt us to share it with scientific community. 

The manuscript was reviewed under MDPI English editing service. The edited version was attached to this response.

Author Response File: Author Response.docx