Severe Fatal Mucormycosis in a Patient with Chronic Lymphocytic Leukaemia Treated with Zanubrutinib: A Case Report and Review of the Literature

Round 1

Reviewer 1 Report

The authors present a very interesting case of disseminated mucormycosis in a patient with heavily-treated CLL. The manuscript contains very nice images of the lesions and the pathology.

The manuscript contains innumerable grammatical and spelling errors throughout, making it difficult to read.

The introduction is too long and needs to be completely rewritten. Most of what is there now has nothing to do with the paper. The introduction should be more focused: a few sentences about [1] how patients with CLL are immunocompromised (B-cell function, hypogammaglobulinemia), [2] how most CLL patients are currently treated with BTK inhibitors at some point during their course, and [3] how invasive fungal infections have been reported with BTK inhibitors. The rest of the introduction is not relevant to the case.

The manuscript contains innumerable grammatical and spelling errors throughout, making it difficult to read.

Author Response

 Dear Editorial Board
Please see the attachment regarding Review #1. 

Regards

Author Response File: Author Response.docx

Reviewer 2 Report

The authors present the course of a female patient with CLL and mucormycosis. The manuscript is mainly well written. However, there are more larger and informative case series on this fungal infection.

I have some comments:

Table 1: which of the risk factors mentioned here are novel?

Please check Ref. N. 6. In the abstract I cannot find data on antifungals as risk factor for mycomycosis

Table 2: why were rituximab and bendamustine given sequentially? this approach is rare in CLL

Table 2: not all agents are chemotherapy, I suggest rather to write anti-tumor agents

please check spelling of anti-infective drugs

Figure 2 and 3, fungi should be shown more clearly

Some parts of the discussion are quite diffuse

There are some spelling mistakes

As far as I can see autopsy was not performed. Why were detailed genetic analyses performed only after death and not before?

Why was the fungal infection resistant to L-Amb?

I suggest to shorten with case report significantly and to present it more clearly

 

 

 

 

 

might be improved

Author Response

Dear Editorial Board,
Please see the attachment regarding Reviewer #2. 

Regards

Author Response File: Author Response.docx

Reviewer 3 Report

The authors have described an intricate case detailing the clinical progression and histopathological findings in a patient with CLL who suffered from mucormycosis. This work emphasizes the limitations of serological findings and the role of combination therapy.

 

Major Comments:

1.The presented case does not seem unusual given the patient's neutropenia and skin lesions. One would typically consider invasive mold infections like mucormycosis or fusariosis as top of differentials. Classically, the factors such as prior azole use, the presence of sinusitis, lung nodules, and pleural effusions that differentiate from aspergillosis.

2. Despite the title emphasizing an "unusual histopathological presentation," there's inadequate discussion on the histopathological findings. Comparing these findings with previously reported cases would interest the readers.

3. The low sensitivity of culture and serological tests for mold infections is well-documented. Hence, in terms of presenting novel insights, this manuscript appears to be lacking.

Minor Comments:

Line 108: Typo “Daptomycin"

Line 110: Elaborate on the degree and duration of neutropenia. Was it prolonged or profound? This is essential information, considering the potential for invasive mold infection.

Line 110: "Weak positive" is ambiguous. The authors should provide objective data, especially considering previous studies/guidelines emphasizes.

Line 112: Clinical findings must include more information on sinus and lung findings (both physical and imaging), as these sites are common infection sites for mucormycosis patients.

Line 151: The dosage of L-Amb is crucial and should be detailed.

Line 188: The cited literature regarding the blood culture positivity rate appears outdated. The authors might benefit from referencing more recent studies.

Author Response

Dear Editorial Board
Please see the attachment regarding Review #3.

Regards

Author Response File: Author Response.docx

Round 2

Reviewer 2 Report

The manuscript has been approved by the modifications made by the authors

largely fine

Author Response

#2 Reviewer 

Dear Editorial Board,
Thank you for reviewing our manuscript.

We appreciate that our revised paper addresses Reviewer’s suggestions and is now worthy of being published

Reviewer 3 Report

Thank you for adding the updated reference and clinically relevant information. I think this paper is now useful for readers. 

Minor comments:

Line 50 typo ‘such as’

Line 74 ‘Mucorales’

Line 141 Most of studies set cut of BDG<80. Mucormycocis is well-known to have negative BDG.

Line 188 L-Amb 10 mg/kg is beyond the recommendation 5mg/kg daily, please double check but if it was truly given, you can keep this statement.

Author Response

#3 Reviewer Comments

Dear Editorial Board,
Thank you for reviewing our case report manuscript.

We appreciate that our revised paper addresses Reviewer’s suggestions and is now worthy of being published

The minor issues are here listed.

C.1: Line 50 typo ‘such as’
A.1: Corrected as suggested.

C.2: Line 74 ‘Mucorales’.
A.2: Corrected as suggested

C.3: Line 141 Most of studies set cut of BDG<80. Mucormycocis is well-known to have negative BDG.
A.3: According to the comment we deleted the part of the text mentioning the weak positivity for BDG.

C.4:Line 188 L-Amb 10 mg/kg is beyond the recommendation 5mg/kg daily, please double check but if it was truly given, you can keep this statement.
A.4: We double checked and we confirm the L-Amb dosage is correctly reported.

 

Hopefully these reviews will meet Reviewer’s observations.