Hemophagocytic Syndrome in a Patient with ALL: Morphology Still Matters

Round 1

Reviewer 1 Report

Dear authors

Your case report is very interesting and may help the clinicians to recognize and treat such a case. Besides, you need a minor revision of your article.

 Point 1.

 Line 82. Your sentence ends with the word while. What do you mean?

Line 90. You rather mean patient instead of patients

Lines 102-104. Indeed, CMV infection, in a study with involvement of 734 plasma samples from 95 patients affected by acute leukemia undergoing chemotherapy, CMV was….

Line 118. In some parameters you refer the normal values, while in others, as in IL, do not.

Line 120. Normally the evaluation of triglycerides. What do you mean?

Line 121, 187. You mean recommendations instead of indications?

Line 128. These…You mean this? It seems that the sentence is not finished.

Line 134 in->of

Line 147. The word that to be removed.

Line 152. Add the word the before minimum

Line 158. Ferritin instead of ferritinemia

Line 162. Instead of medicated for->due to

Line 163, 169. cause->because

Line 174. based on->according to, remove the word work.

Point 2.

You can write the criteria of Histiocyte Society recommendations where you based your diagnosis, ex. Add a table.

Point 3.

In figure place an index determining the cells you describe.

             

Author Response

Point 1:

 Line 82. Your sentence ends with the word while. What do you mean?

Line 90. You rather mean patient instead of patients

Lines 102-104. Indeed, CMV infection, in a study with involvement of 734 plasma samples from 95 patients affected by acute leukemia undergoing chemotherapy, CMV was….

Line 118. In some parameters you refer the normal values, while in others, as in IL, do not.

Line 120. Normally the evaluation of triglycerides. What do you mean?

Line 121, 187. You mean recommendations instead of indications?

Line 128. These…You mean this? It seems that the sentence is not finished.

Line 134 in->of

Line 147. The word that to be removed.

Line 152. Add the word the before minimum

Line 158. Ferritin instead of ferritinemia

Line 162. Instead of medicated for->due to

Line 163, 169. cause->because

Line 174. based on->according to, remove the word work. 

Response 1: I accept your corrections and modify the text as well as advice

 

Point 2: You can write the criteria of Histiocyte Society recommendations where you based your diagnosis, ex. Add a table.

Response 2: Thank you for your advice, I have entered the table in such a way as to make the criteria more identifiable

 

Point 3: In figure place an index determining the cells you describe.

Response 2: I modified the image in such a way as to highlight the elements described more easily

 

Thank you for your very important advice, please see the attachment.

Sincerely, Dr. Duminuco

Author Response File: Author Response.pdf

Reviewer 2 Report

HLH in the context of B-ALL is rare.  The authors present a 23 yo male who meets clinical HLH criteria with morphologic evidence for hemophagocytosis.  My comments/questions are:

1. If the following were evaluated at the time of HLH diagnosis, please include them in the presentation:  sIL-2R (sCD25), CXCL9, liver function tests, EBV viral load. 
2. Please include the normal value for IL-6 (e.g. <1.8 pg/mL)
3. The term Macrophage Activation Syndrome (MAS) is reserved for patients with HLH in the context of Rheumatoid Arthritis.  I therefore suggest that the authors replace MAS with HLH throughout.
4. A prior publication describes HLH in association with B-ALL (PMID 16856156). The authors should cite and discuss the findings in this publication.
5.  Standard HLH therapy per HLH-94 includes dexamethasone and etoposide.  The authors imply that steroids alone (line 133-134) is first line therapy.  They should correct this. Perhaps in this case there was a reason why etoposide was avoided (e.g. elevated bilirubin) - if so, the authors might clarify.  I agree that Anakinra is a viable option.
6. Was there an family history of HLH?  Was any genetic testing for germline mutations that predispose to HLH done?
7. While generally well written, a number of sentences run on too long.

Author Response

Point 1: If the following were evaluated at the time of HLH diagnosis, please include them in the presentation:  sIL-2R (sCD25), CXCL9, liver function tests, EBV viral load.

Response 1: I entered the liver function and EBV viral load exams. sIL-2R (sCD25) and CXCL9 were not tested because not available at that time at our center

 

Points 2 and 3: Please include the normal value for IL-6 (e.g. <1.8 pg/mL); The term Macrophage Activation Syndrome (MAS) is reserved for patients with HLH in the context of Rheumatoid Arthritis.  I therefore suggest that the authors replace MAS with HLH throughout.

Response 2 and 3: I changed the text as well as she advised me

 

Points 4: A prior publication describes HLH in association with B-ALL (PMID 16856156). The authors should cite and discuss the findings in this publication.

Response 4: Thanks for your valuable advice. I proceeded to include this work in text and among the references

 

Points 5: Standard HLH therapy per HLH-94 includes dexamethasone and etoposide.  The authors imply that steroids alone (line 133-134) is first line therapy.  They should correct this. Perhaps in this case there was a reason why etoposide was avoided (e.g. elevated bilirubin) - if so, the authors might clarify.  I agree that Anakinra is a viable option.

Response 5: Right observation. I modified the text in such a way as to better explain and motivate our choice, considering the genesis probably due to CMV infection, rather than strictly related to the neoplastic disease

 

Points 6: Was there an family history of HLH? Was any genetic testing for germline mutations that predispose to HLH done?

Response 6: We did not perform any genetic testing for germline mutations because family history for HLH was completely negative

 

Points 7: While generally well written, a number of sentences run on too long.

Response 7: I have proceeded to shorten some of the sentences that are too long

 

Thank you for your valuable advice, please see the attachment.

Sincerely, Dr. Duminuco

Author Response File: Author Response.pdf