Refractory/Relapsed Classic Hodgkin Lymphoma Mimicking Disseminated Tuberculosis

1^st reviewer comments:

Reply:

Abstract: the authors should use MeSH terms as keyword and cHL as the keyword is repeated three times.

Thank you. We replaced repeated “cHL” with appropriate MeSH terms and revised the keywords accordingly.

Introduction: Symptomatology of HL should be omitted due to the fact that it is common knowledge. Section on TB should be expanded by providing epidemiological data in developing countries.

Thank you. We removed the general symptomatology of HL and expanded the TB section with relevant epidemiological data from developing countries.

(IPS missing) and given ABVD as initial therapy. Rationale for this choice must be explained in the Case or Discussion section.

Thank you very much for this important remark. We have now added the IPS score and provided a clear rationale for initiating ABVD in the Case section.

Furthermore, interim PET showed Deauville 5 and the statement that the patient partly responded to this regimen is untrue due to the fact that Deauville 5 is progressive disease. Due to drug shortage, the patient was irradiated. The data on modality and doses are missing

Thank you for this valuable correction. We have revised the statement to reflect that Deauville 5 indicates progressive disease. Details on the radiotherapy modality and doses have also been added.

The part on BEACOPP is adequate. I would like to see a brief lab work-up in January 2024.Part on TB work-up does not need to be changed

Thank you. We’re glad the BEACOPP section is adequate. A brief summary of the January 2024 lab work-up has been added as requested. The TB work-up section remains unchanged.

I would like to see a rationale of BV, checkpoint inhibitor combination with standard salvage therapy (why not the use of bendamustine). The authors should also provide AEs if they were noted.The section on ASCT should be expanded (harvesting, conditioning regimen).

Thank you for your comment. As the patient had already received two cycles of DEHAP as recommended by the ESMO guidelines, we opted to add brentuximab vedotin and nivolumab instead of switching to BvB to enhance remission depth. This approach is in line with ESMO guidelines, which recommend achieving PET negativity prior to ASCT. We have also expanded the ASCT section to include details on mobilization, collection, and conditioning and the adverse effect were outlined in the manuscript.

Was PET done after the transplant to confirm CMR due to the fact that this is a high risk patient?DiscussionThe nivolumab maintenance should be included in the case report.

Thank you. We clarified that a post-transplant PET was performed to confirm CMR. Nivolumab maintenance has also been added to the Case and Discussion sections.

Since this is a case report, not a review I suggest that the authors focus on the case and the rationale of the treatment with adequate references. The part on the evolving paradigm in R/R cHL management should be omitted.

Thank you for the suggestion. We have removed the section on the evolving paradigm in R/R cHL.

The list of references is confusing and the authors must  rewrite this part.

Thank you. We have revised and reorganized the reference list to improve clarity and consistency.

Furthermore, I can not find the figures.Concerning ethical issue, Ihas the patiunet given the consent to publish this data?Major revision is needed.

Thank you. The missing figures were due to a technical issue and have now been properly included. Patient consent for publication was obtained and is now clearly stated in the manuscript. We appreciate your guidance and have made the necessary major revisions.

2^nd reviewer comments:

Replies:

It is not indicated in the "Case Presentation" whether ethical principles for biomedical research involving human subjects were followed and whether the patient signed an informed consent. I suggest including the medical history of the case (e.g., if the patient has lately been vaccinated for Bacillus Calmette–Guérin (BCG) and clinical data, including blood count (WBC, CRP, etc.), to complete the clinical picture.

Thank you for the valuable feedback. We have now stated adherence to ethical principles and confirmed that informed consent was obtained. The patient's medical history, including BCG vaccination status, and relevant clinical data (WBC, CRP, etc.) have been added to complete the clinical picture.

I would suggest specifying when the patient mobilized and collected stem cells.

Thank you. We have specified the timing of stem cell mobilization and collection in the Case section.

Furthermore, to have a visual overview of the patient's clinical-therapeutic evolution, a figure with the timeline of the case report would be immediate.

Thank you for the excellent suggestion. We have added a timeline figure to visually summarize the patient’s clinical and therapeutic course.

In the “Discussion”, I would add the references related to the Keynote-204 and Pembro-GVD trials.

Thank you. We had originally included this part but omitted it following Reviewer 1’s suggestion to focus strictly on the case.

All abbreviations must be defined at their first occurrence in the text, without necessarily repeating them subsequently (i.e., tuberculosis, Brentuximab vedotin, complete remission, classic Hodgkin lymphoma).

Thank you. All abbreviations have now been defined at their first occurrence and used consistently throughout the text.

Pay more attention to the "consecutio temporum."

The figures are missing, and there is a discrepancy in the references (which are listed twice).

Thank you. The issue with the missing figures and duplicate references was technical and has been resolved in coordination with the editor.