Rare Clinical Symptoms in Hairy Cell Leukemia: An Overview

The authors reviewed what had been published over approximately 50 years,  from 27 January 1980 to August 2024,  to capture the incidence of rare clinical conditions associated with HCL. Response: The authors thank the reviewer for their feedback.

 TYPOS

1

The authors report 'et al'  which I suggest always change to 'et al.' Response: Corrected as indicated

2

Line 62:

newly-diagnosed

Please, change with newly diagnosed Response: Corrected as indicated

3

Line 90

moderately-abundant

Please, change with moderately abundant Response: Corrected as indicated

4

Line 103 and line 339:

extra nodal

Please, change with extra-nodal Response: Corrected as indicated

5

Line 121

Skin Symptoms

differentiated with other cancers,

 Please,change with:  differentiated from other cancers, Response: Corrected as indicated

6

line 138

sometimes in  form of plaques

 Please change with: sometimes in the form of plaques Response: Corrected as indicated

7

Line 141

tssue

 Please change with: tissue Response: Corrected as indicated

8

The roentgenogram (or roentgenograph) is an old-style synonymous term of x-rays Response: Corrected as indicated

9

line 138

sometimes in  form of plaques

 Please change with: sometimes in the form of plaques Response: Corrected as indicated

10

Line 191

and is  more useful in the differentiation of HCL lesions and malignant bone tumors.

Please change with:

and is more helpful in differentiating HCL lesions from malignant bone tumors. Response: Corrected as indicated

11

Line 197

maginification

Please change with maginification

Response:Changed as requested

12

Line 227

is not related

Please change with unrelated Response: Corrected as indicated

13

Line 243:

due orbital fracture

 Please change with: due to orbital fracture Response: Corrected as indicated

14

Line 247

Retinopathy and visual disturbance due to intraretinal hemorrhage was reported

 Please change with: Retinopathy and visual disturbance due to intraretinal hemorrhage were reported Response: Corrected as indicated

15

Line 257

Most of them had

Please change with: Most had Response: Corrected as indicated

16

Line 262

has only been rarely reported

Please change with: rarely been reported Response: Corrected as indicated

17

Line 281

patient

 Please, change with: patients Response: Corrected as indicated

18

line 287

can ocassionally mimic infective endokarditis

 Please change with: can occasionally mimic infective endocarditis Response: Corrected as indicated

19

Lines 294-295

second degree mitral and aortic valve insufficiency and reduced ejection fraction....

 Please change with: second-degree mitral and aortic valve insufficiency and a reduced ejection fraction Response: Corrected as indicated

10

Line 305

association

 Please change with: an association Response:

MINOR COMMENTS

1

The methods are mentioned in the abstract but not in the text of the paper where they deserve a section. A PRISMA flow diagram describing the result of the selection process of selected papers can be useful. Response: The methods is included in the main text, in the introduction

2

Line 69-Common clinical presentation

his paper focuses on the rare clinical features of HCL. This section reports in greater detail the typical clinical characteristics already mentioned in the introduction and in addition, also data about the diagnostic approach and the genetic characteristics of HCL. I would suggest that authors limit this information to the introduction. Response: We removed subchapter „Common clinical presentation“ in the revised paper

3

Lines 111-113

Direct infiltration of the skin by leukemic cells 111 is defined as infiltration of the epidermis, the dermis, and the subcutaneous tissue by 112 leukemic cells

Lines 117- 119

 the diagnosis of leukemia cutis is performed based on the histopatology 118 of skin biopsy and the immunophenotyping of neoplastic cells [27,28].

 I would mention the two concepts in the same sentence Response: We combined this two sentences in the revised version.

4

Table 1 is rather chaotic and often unclear.

The authors should simplify it by,excluding obvious information, those that cannot be effectively summarized and reporting only the essential and informative points

 Some typos:

Boone

 Chest X-rey  

 invasion of HCL cells to CNS Response: Table 1 was reedited according to the rviewer suggestion

5

Line 147

The most common skin symptoms in HCL patients are bacterial or viral infections.

 I would change with: Due to the increased risk of infections, the most common skin involvement in patients with HCL is due to bacterial or viral infections. Response: Changed as indicated

6

Lines 155-156:

 Bone symptoms in HCL include osteolytic and osteoblastic lesions, severe osteopo rosis, aseptic necrosis of the femoral head and multifocal lytic changes

 I would change to: the most common orthopedic complications in HCL are due to osteolytic and osteoblastic lesions, severe osteoporosis, aseptic necrosis of the femoral head and multifocal lytic changes Response: Changed as indicated

7

Lines 159-165

The authors can summarize the text by writing that bone lesions can be early, appear over the years and even in patients in remission Response: Added as indicated

Pulmonary symptoms.

 I would limit the report to the rate of patients experiencing the rarest forms of lung infection.I would also mention which treatments are associated with a greater incidence of opportunistic lung infections.

Moreover, I would mention the incidence of lung cancers Response: Reedited as indicated

8

Line 253

Sudden hearing loss in patients with leukemia can be related to leukemic infiltration, hemorrhage, and infection.

 Line 258

Such sudden hearing loss in patients with leukemia can be attributed to leukemic infiltration, hemorrhage, blood hyperviscosity and infec tion

 The authors should eliminate this repetition Response: Repetition was eliminated

9

Line 299

 Rheumatological symptoms related either to the hematological malignancy or the  immune system have been rarely reported in HCL patients .

 I would change 'the immune system' with disease-related immune dysregulation

 Moreover, please change:  have been rarely reported. with: have rarely been reported Response: Changed as indicated

10

 I suggest that the authors summarize the text as much as possible, eliminating too detailed descriptions of the reported clinical events. Response: The text was reduced as indicated. In particular, Figure 1   and Subchapter „2. Common clinical presentation“ were rmoved. In addition, some sentences were removed from other subchapters