Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review

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Al-Ansari" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Objective This systematic literature review aimed to study the relationship between CML and hearing loss. Database review Chronic myeloid leukemia (CML) is a hematological malignancy associated with high levels of white blood cells (WBCs). Changes in otolaryngology are observed in CML. Methodology This systematic literature review of the literature was conducted by searching the MEDLINE/PubMed, Scopus, WPRIM, LILAC Sand SciELO databases. Studies published between 2013 and 2023 including available in scientific papers as randomized control trials (RCTs), clinical trials, observational studies such as case-control, cross-sectional and cohort studies, whether retrospective or prospective, as well as review studies, case reports, and case series, that met inclusion criteria were included. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to evaluate the quality of studies. Results Of the 142 identified articles, 13 were included for final evaluation with a total sample size of 75 cases diagnosed with CML with hearing defect. CML patients with WBCs above 250 x 109/L, mean WBC level associated with hearing loss of 554x 109/L, were at higher risk of ototoxicity. Males accounted for 85% of cases; with a mean age of 38.9 years. Hearing loss as the first manifestation of CML was among 61.5% of cases, it was bilateral in 83.3% of cases, and in 90% of cases were irreversible defect, with proportion of reversible vs irreversible cases is 1:10. Conclusion Acute sudden hearing loss has been associated with high levels of WBC in patients with CML. Neither aggressive leukoreduction nor leukapheresis has positive effect on the reversibility of the hearing loss. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/13-974", "name": "Coexisting of hearing loss and chronic myeloid leukemia - A systematic..." } } ] } Home Browse Coexisting of hearing loss and chronic myeloid leukemia - A systematic... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Al-Ansari K, Woodman A, Mohammed Alghamdi L et al. Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] . F1000Research 2025, 13 :974 ( https://doi.org/10.12688/f1000research.151670.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Systematic Review Revised Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] Khadija Al-Ansari 1 , Alexander Woodman 2 , Lojin Mohammed Alghamdi 3 , Turki Omaish Al otaibi https://orcid.org/0009-0002-4671-882X 4 , Rehab Y. Al-Ansari https://orcid.org/0000-0003-4331-5769 5 Khadija Al-Ansari 1 , Alexander Woodman 2 , [...] Lojin Mohammed Alghamdi 3 , Turki Omaish Al otaibi https://orcid.org/0009-0002-4671-882X 4 , Rehab Y. Al-Ansari https://orcid.org/0000-0003-4331-5769 5 PUBLISHED 10 Sep 2025 Author details Author details 1 Department of Otorhinolaryngology, King Hamad University Hospital, Muharaq, Bahrain 2 School of Health Sciences, School of Health Sciences, University of Salford, Manchester, England, UK 3 Department of Respiratory Therapy, Armed Forced Hospital, Najran, Saudi Arabia 4 Pediatric Intensive Care Unit, Pediatric Department, King Fahd Military Medical Complex, Dhahran, Saudi Arabia 5 Adult Hematology Unit, Internal Medicine Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia Khadija Al-Ansari Roles: Formal Analysis, Methodology Alexander Woodman Roles: Investigation, Validation, Writing – Review & Editing Lojin Mohammed Alghamdi Roles: Data Curation, Formal Analysis, Validation Turki Omaish Al otaibi Roles: Writing – Review & Editing Rehab Y. Al-Ansari Roles: Data Curation, Formal Analysis, Writing – Original Draft Preparation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Objective This systematic literature review aimed to study the relationship between CML and hearing loss. Database review Chronic myeloid leukemia (CML) is a hematological malignancy associated with high levels of white blood cells (WBCs). Changes in otolaryngology are observed in CML. Methodology This systematic literature review of the literature was conducted by searching the MEDLINE/PubMed, Scopus, WPRIM, LILAC Sand SciELO databases. Studies published between 2013 and 2023 including available in scientific papers as randomized control trials (RCTs), clinical trials, observational studies such as case-control, cross-sectional and cohort studies, whether retrospective or prospective, as well as review studies, case reports, and case series, that met inclusion criteria were included. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to evaluate the quality of studies. Results Of the 142 identified articles, 13 were included for final evaluation with a total sample size of 75 cases diagnosed with CML with hearing defect. CML patients with WBCs above 250 x 10 9 /L, mean WBC level associated with hearing loss of 554x 10 9 /L, were at higher risk of ototoxicity. Males accounted for 85% of cases; with a mean age of 38.9 years. Hearing loss as the first manifestation of CML was among 61.5% of cases, it was bilateral in 83.3% of cases, and in 90% of cases were irreversible defect, with proportion of reversible vs irreversible cases is 1:10. Conclusion Acute sudden hearing loss has been associated with high levels of WBC in patients with CML. Neither aggressive leukoreduction nor leukapheresis has positive effect on the reversibility of the hearing loss. READ ALL READ LESS Keywords Chronic myeloid leukemia, hearing loss, hyperleukocytosis, sensorineural hearing loss management, prevention. Corresponding Author(s) Rehab Y. Al-Ansari ( [email protected] ) Close Corresponding author: Rehab Y. Al-Ansari Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Al-Ansari K et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Al-Ansari K, Woodman A, Mohammed Alghamdi L et al. Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] . F1000Research 2025, 13 :974 ( https://doi.org/10.12688/f1000research.151670.2 ) First published: 28 Aug 2024, 13 :974 ( https://doi.org/10.12688/f1000research.151670.1 ) Latest published: 10 Sep 2025, 13 :974 ( https://doi.org/10.12688/f1000research.151670.2 ) Revised Amendments from Version 1 In this version we revised the abstract and the Conclusion part as per reviewer recommendation. Also, we added Table 2 for better view of quality assessment of each study that was included in our review. Also, by adding Table 2 we change name of previous Table 2 to be Table 3. Adding to that, we wrote points of strength and recommended research at the end of the Discussion. In this version we revised the abstract and the Conclusion part as per reviewer recommendation. Also, we added Table 2 for better view of quality assessment of each study that was included in our review. Also, by adding Table 2 we change name of previous Table 2 to be Table 3. Adding to that, we wrote points of strength and recommended research at the end of the Discussion. See the authors' detailed response to the review by Ikhwan Rinaldi READ REVIEWER RESPONSES Introduction Chronic myeloid leukemia (CML) is one of the myeloproliferative neoplasms (MPNs), also known as chronic myelogenous leukemia or chronic granulocytic leukemia. With about 15% of adult leukemias being CML, this cancer starts in the hematopoietic cells of the bone marrow and spreads into the blood. 1 – 3 CML can also cause thrombocytopenia or platelet dysfunction resulting in bleeding, thrombocytosis resulting in thrombosis or priapism, basophilia resulting in histamine release, and upper gastrointestinal ulcers. According to the National Cancer Institute Surveillance and Epidemiology for 2016–2020, the prevalence was 1.9/per 100,000 population/year, and the death rate from CML was 0.3/per 100,000 population/year. 2 Although predisposing risk factors are unknown, CML, BCR-ABL1-positive, consists predominantly of proliferating granulocytes and has a Philadelphia chromosome/ t (9;22)(q34;q11.2) translocation in more than 90% of cases; less than 5% may be BCR/ABL negative mutations. 4 – 6 The disease progresses through three phases - chronic, blast, and accelerated phases, with most patients in the chronic phase and diagnosed by routine complete blood count (CBC). CML in the chronic phase most commonly presents with symptoms associated with anemia (e.g., fatigue and malaise) and splenomegaly (e.g., early satiety, fullness in the left upper quadrant, or pain). As CML enters the accelerated or blast phase, symptoms such as headaches, bone pain, fever, joint pain, bleeding, infections, and lymphadenopathy become more common. Each phase has specific laboratory features, prognosis, and treatments. 5 – 7 Although CML is considered a disease of the middle-aged and elderly, reported cases have been found in the pediatric and younger population, generally more aggressive with atypical presentation than in adults. 1 , 8 , 9 Similar to adults, around 95% of pediatric patients with CML are in the chronic phase (CML-CP). 1 , 10 Most adult cases diagnosed with CML were asymptomatic, with incidental findings of high white blood cell (WBC) counts on routine blood work. The most common symptoms of CML are fatigue, weight loss, exercise intolerance, fever and increased sweating, early satiety, decreased food intake, and right, and/or left upper quadrant pain due to liver and/or spleen enlargement. 5 , 6 , 11 In addition to the typical and established manifestations of CML, cases with atypical symptoms have been reported. Thus, although hearing loss is associated with acute leukemia and is less common in patients with CML presenting at later stages of the disease, recent data report sudden hearing loss in patients with CML. 12 – 14 Hearing loss in CML may be unilateral or bilateral sensorineural hearing loss (SNHL), or it may begin as unilateral and then progress into bilateral. Since sudden hearing loss as an initial manifestation of the underlying hematological disease is rare, the pathogenesis of this clinical symptom is complex, including leukostasis, cochlear leukemic infiltration, hyper-viscosity syndrome, thrombo-hemorrhagic complications, and infections. 1 , 3 , 15 In addition, the pathophysiology of this coexistence between CML and hearing loss or impairment varies. Some researchers attribute it to increased viscosity due to high WBC, congestion and thrombus formation, labyrinthitis or inflammation, others to coagulation disorders associated with CML or bone disease, and cochlear ossification. 10 – 15 This systematic literature review aims to identify and examine CML studies reporting hearing loss in 2013-2023, taking into consideration the rarity of cases and the complex nature of the combination of the two health conditions. Methods Study design This systematic review was developed after an approval for the research from the Armed Force Hospitals Eastern Region Institutional Review Board (IRB), protocol No. AFHER-IRB-2023-035. The review protocol was published in the international prospective register of systematic reviews (PROSPERO) website - registration number CRD42024551404. The databases were searched between January 3rd 2023 to July 22 2023. The search and report process followed the statement and flowchart of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) ( Figure 1 ). The full texts of potentially eligible records were retrieved and assessed for eligibility. Figure 1. Study identification, screening, and inclusion guided by PRISMA. Search strategy Five electronic literature databases were searched that may potentially cover the research aim: MEDLINE/PubMed, Scopus, WPRIM, LILAC, and SciELO. The search used the Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH Terms) expressed in English through a combination of key concepts such as ‘Leukemia,’ ‘Myelogenous,’ ‘Chronic,’ ‘Hearing Loss,’ ‘Leukocytes, ‘Sense Organs.’ Next, a manual search was carried out using links to the identified articles. An independent medical librarian reviewed the search results for completeness and accuracy. Eligibility criteria Scientific articles published and available in scientific databases in English, including randomized control trials (RCTs), clinical trials, observational studies such as case-control, cross-sectional and cohort studies, whether retrospective or prospective, as well as review studies, case reports, and case series published between 2013 and 2023 that could potentially address the aim of this study, were considered eligible for inclusion. In addition, due to the limited number of studies available, letters to the editor that provided a full explanation of the case and were consistent with the aim of this study were considered appropriate for inclusion. Articles published before 2013, editorials, and publications written in a language other than English were excluded. Selection of studies and quality assessment The first author searched and extracted research from scientific databases. The second author reviewed the titles and abstracts of the extracted articles to ensure that the studies were appropriate and met the inclusion criteria. The first and third authors performed a thorough full-text evaluation of the articles, duplicates and studies that did not meet the inclusion criteria were excluded. At the final stage, the remaining articles were critically reviewed and analyzed to be included in the final list of articles for further analysis by the first author. Methodological quality or internal validation of a systematic review is an important step to eliminate the risk of bias. Therefore, the first and second authors were (independently) assigned to assess the quality of the included studies using Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Analytical Cross-Sectional Studies, as well as, for other study design each in its related JBI checklist (case report and case seris). 16 The Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Analytical Cross-Sectional Studies contained of 8 questions with 4 rating score in each (yes, no, unclear, and not applicable). Questions about clarity of inclusion criteria, if the description of the study subject in detail, if exposure measured, if objective, standard criteria used for measurement of the condition, if confounding factors identified, strategies to deal with confounding factors, if the outcomes measured in a valid and reliable way, and lastly if appropriate statistical analysis used was used. 16 Results The database search resulted in 134 studies. Eight articles were included, sourced from the reference lists identified through the original database search. After removing duplicates (105), the relevant articles and publications were selected in two stages. During the first stage, the titles and abstracts of the articles were screened, and non-relevant articles were excluded. 17 In the second stage, the full text of included studies was explored. Articles published before 2013, editorials and written in a language other than English were excluded. 7 As a result, 13 studies were selected for a final review ( Figure 1 ). Characteristics of the included studies Of the included 13 studies published between 2013 and 2023, 1 was a case series, 11 case reports, and 1 observational cross-sectional study. As shown in Table 1 , all studies analyzed hearing loss. The sample size for all 13 studies was n = 75 cases with a diagnosis of CML in which hearing loss or defect was studied or confirmed. 17 – 29 Of these, 30 cases (40%) with confirmed sudden hearing loss, 38 cases (50.6%) with a positive audiological examination for hearing impairment ( Table 1 ). All case studies of CML were in the chronic phase (CP) at the time of diagnosis, and only one case had a negative Philadelphia chromosome (BCR/ABL) gene mutation (1.3%). 21 Table 1. Characteristics of included studies (n = 13). Author, Year Country Type of study Study sample n Site of hearing loss Onset duration Cytoreduction Leukapheresis Reversibility Alimam et al., 2013 17 United Kingdom Case report 1 Bilateral deafness Acute, sudden prior to CML diagnosis Hydroxyurea followed by Imatinib Yes No Kapur et al., 2013 18 USA Case report 1 Bilateral deafness Sudden after diagnosis as CML by 9 days Hydroxyurea followed by nilotinib No Not with cytoreduction *Achieved post cochlear implants Ejele et al., 2013 19 Nigeria Case report 1 Bilateral sudden sensorineural hearing loss Prior to CML diagnosis Hydroxyurea followed by imatinib No No Diao et al., 2014 20 China Case report 1 Unilateral sudden sensorineural hearing loss and tinnitus Sudden prior diagnosis as CML Hydroxyurea + hyperbaric oxygen and intratympanic steroid followed by Imatinib No No Sanyaolu et al., 2014 21 Nigeria A cross-sectional hospital-based study 58 subjects with n = 13 cases of self-reported hearing loss Nine (69.2%) had bilateral hearing impairment and 4(30.8%) had unilateral hearing loss Sudden in 9(69.2%) and 7 (53.8%) the hearing loss preceded the diagnosis of CML NA NA NA Tang et al., 2017 22 USA Case report 1 Bilateral sensorineural hearing loss Sudden after diagnosis as CML TKI (unknown) Yes Not with cytoreduction *Achieved post cochlear implants Cass et at., 2018 23 USA Case report 1 Sudden bilateral hearing loss, tinnitus, and vertigo Sudden after diagnosis as CML Hydroxyurea followed by Dasatinib No No Aremu et al., 2018 24 Nigeria Case report 1 Bilateral sudden sensorineural hearing loss Sudden sensorineural hearing loss prior to CML diagnosis Cyclophosphamide, and hydroxyurea No Yes Ugwu et al., 2021 25 Nigeria Case report 1 Bilateral sensorineural deafness Started shortly post diagnosis Hydroxyurea No Yes Zeng et al., 2021 26 China Case report 1 Bilateral Hearing Loss and Unilateral Cochlear Ossification Post diagnosis of CML by 5 days Hydroxyurea treatment for 10 days; then shifted to imatinib (0.4 g, once daily) for 8 months No Not with cytoreduction *Achieved post cochlear implants Chishaki et al., 2021 27 Japan Case report 1 Unilateral (LT) sided hearing loss Acute, sudden prior to CML diagnosis Hydroxycarbamide (Hydroxyurea) and prednisolone followed by Dasatinib as maintenance Yes No Tandon et at., 2021 28 United Kingdom Case series 6 Bilateral sudden sensorineural hearing loss 1 known CML before, 5 sudden hearing loss prior to CML diagnosis 5-Cases stared with Hydroxy urea then shifted to TKI (imatinib or nilotinib) 1- case treated with Imatinib as up-front medication. 2- cases required cytarabine induction along with Hydroxy urea 1- case required intrathecal prednisolone (40 mg/m2 /d for 5 days) 1- case getting methotrexate, prednisolone (40 mg/m2/d for 5 days) No 5 out of 6 irreversible Yang 2022 29 Philippines Case report 1 Bilateral sudden sensorineural hearing loss Prior to CML diagnosis NA NA NA Further analysis of the included studies indicated that the majority of clinical cases were from Nigeria 30.7% (n = 4), 19 , 21 , 24 , 25 followed by the United States 23% (n = 3). 18 , 22 , 23 The age of detected cases ranged from 21 to 100 years, with a mean age of 38.9. 17 – 29 Most of the cases were reported among male patients. 17 , 18 , 21 – 29 Sudden hearing loss was the first manifestation prior to the diagnosis of CML in 61.5% (n=8) of the studies. 17 , 19 , 20 , 24 , 27 – 29 All studies showed sudden onset of hearing loss, with the exception of a cross-sectional study in which 38 out of 58 cases were found to have impaired hearing loss after audiological screening (65.5%) 21 ( Table 1 ). In terms of site of hearing loss, the analysis showed 2 studies with unilateral hearing loss and 11 studies with bilateral hearing lose. Thus, in 25 of 30 cases there was bilateral sudden hearing loss (83.3%). While patient management varied from study to study, hydroxyurea was used as the first line of cytoreduction in all cases. Three studies used leukapheresis/plasmapheresis 17 , 22 , 27 ( Table 1 ). Of 30 cases of deafness, 3 (10%) were reversible after assertive treatment, 24 , 25 , 28 and 3 (10%) achieved post cochlear implants 18 , 22 , 26 ( Table 1 ). An irreversible hearing loss defines as persist ototoxic condition after medical or /and surgical treatments modality, with follow up after management for certain period of time. Quality of the included studies The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to evaluate the quality of studies. 16 Of included studies, one case series study by Tandon et at. (2021) showed a low risk of bias, with 80–90% meeting the criteria of JBI checklist. 28 Of the eleven case reports, one presented a moderate risk of bias, with 50–62% meeting the JBI criteria; the remaining ten reports had a score greater than 75% to 100%, indicating a low risk of bias. A low risk of bias was found for cross sectional study by Sanyaolu et al. (2014), with JBI criteria ranging from 87.5% to 100%. 21 The only limitation in case reports is that some articles do not include complete blood counts data fully, i.e., platelets and hemoglobin ( Table 2 ). Table 2. JBI risk of bias quality assessment. Author, Year Type of study Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 % Yes Risk Alimam et al., 2013 17 Case report Yes Yes Yes Yes Yes Yes Yes Yes 100% Low risk Kapur et al., 2013 18 Case report Yes Yes Yes Yes Yes Yes Yes Yes 100% Low risk Ejele et al., 2013 19 Case report Yes Yes Yes Yes No Yes Yes Yes 87 % Low risk Diao et al., 2014 20 Case report Yes Yes Yes Yes No Yes Yes Yes 87% Low risk Sanyaolu et al., 2014 21 A cross-sectional hospital-based study Yes Yes Yes Yes Yes Yes Yes No 87% Low risk Tang et al., 2017 22 Case report Yes Yes Yes Yes No No Yes Yes 75% Low risk Cass et at., 2018 23 Case report Yes Yes Yes Yes No No Yes Yes 75% Low risk Aremu et al., 2018 24 Case report Yes Yes Yes Yes Yes No Yes Yes 87% Low risk Ugwu et al., 2021 25 Case report Yes Yes Yes Yes No No Yes Yes 75% Low risk Zeng et al., 2021 26 Case report Yes Yes No Yes Yes Yes Yes Yes 85% Low risk Chishaki et al., 2021 27 Case report Yes Yes Yes Yes No No Yes Yes 75% Low risk Tandon et at., 2021 28 Case series Yes Yes Yes Yes Yes Yes Yes No 87% Low risk Yang 2022 29 Case report Yes Yes Yes Yes No No No No 50% Moderate risk Main outcomes of laboratory tests Further analysis of laboratory data showed high WBC to the level ranged between 555 – 690 × 10 9 /L in 9 of the studies 17 , 18 , 21 – 23 , 26 – 28 ( Table 3 ). Only two cases reported the WBC being 264 × 10 9 /L and 294 × 10 9 /L in 2(15.3%) 20 , 24 and one study showed the highest of WBC level up to 1,343 × 10 9 /L (3.3%). 19 In all cases, the number of leukocytes (WBC) was analyzed (median, mean, or/and average) ( Table 3 ). The WBC count was documented as high but was not actually found in the reports of Ugwu et al., 2021 25 and Nathaniel et al., 2022. 29 None of the studies showed normal or less than 200 WBC levels among CML cases at presentation with hearing loss, confirming a strong correlation between hearing loss and WBC count ( Table 3 ). Table 3. Demographic and complete blood counts analysis in reported cases. Author, Year Age Gender BCR/ABL mutation WBC Platelet Hgb (g/dl) Study remarks Alimam et al., 2013 17 Younge age Male Positive (CP) 605 ×10 9 /l NA NA Cortical deafness is rare and usually occurs after bilateral involvement of the temporal or temporoparietal lobes. CML rarely presents with this pattern. Kapur et al., 2013 18 52 Male Positive (CP) 685 × 10 9 /l 164 ×10 9 /l 9.1 g/dl Central bleeding as a complication of CML may play a role in central hearing loss. In this case, a cochlear implant was required. Ejele et al., 2013 19 24 Female Positive (CP) 1,343 × 10 9 /l 589 × 10 9 /l NA In cases of CML, it is important to have an audiovisual assessment. Diao et al., 2014 20 31 Female Positive (CP) 264 × 10 9 /l NA 9.8 g/dl Sudden hearing loss may be the initial manifestation of hematological disorders, such as CML. Sanyaolu et al., 2014 21 Mean age 47.2 32 Males 26 Females Positive (CP) WBC count 154, 347 ± 63,050 cells/mm3 NA NA Audiometry revealed a higher prevalence of 38 (65.5%) hearing loss in cases diagnosed with CML. All had sensorineural hearing loss. Tang et al., 2017 22 40s Male Positive (CP) 697 × 10 9 /l NA NA Hemorrhage is an alternative etiology, cochlear implantation and vestibular rehabilitation as treatment plans. Cass et at., 2018 23 49 Male Positive (CP) 555 × 10 9 /l NA NA Starting a TKI did not improve hearing even after a decrease in WBC count, which led to the use of a hearing aid. Aremu et al., 2018 24 100 Male Positive (CP) 294.4 × 10 9 /l NA NA It is likely that the leukostatic reaction of the labyrinth and other small arteries was blocked, leading to SSNHL. Ugwu et al., 2021 25 53 Male Negative (CP) NA NA NA The case had a complication from hydroxyurea. Zeng et al., 2021 26 21 Male Positive (CP) 626 × 10 9 /l 358 × 10 9 /l 67 g/dl Cochlear implantation was necessary for the irreversibility of hearing loss and due to the presence of cochlear ossification. Chishaki et al., 2021 27 26 Male Positive (CP) 627 × 10 9 /l 226 × 10 9 /l 8.2 g/dl Infarction and hemorrhage associated with leukostasis can lead to occlusion of the labyrinthine artery. Tandon et at., 2021 28 Mean age 39.5 5 Males 1 Female Positive (CP) Mean 611.5 x 10 9 /L (range, 264-850) NA NA Hearing loss associated with CML was in most cases irreversible even with cytoreduction. Early detection of the disease and aggressive treatment may protect senses. Yang, 2022 29 25 Male Positive (CP) High, exact number NA NA NA Inner Ear Hemorrhage of the causes of Sensorineural Hearing Loss in CML cases Platelet counts were analyzed in 4 studies, 18 , 19 , 26 , 27 three of which reported that platelets were normal and ranged from 164 to 358 × 10 9 /l at the onset of hearing loss 18 , 26 , 27 ( Table 3 ). However, in a study by Ejele et al. (2013) the platelet count was high - 589 × 10 9 /l without documented thrombosis. 19 Hemoglobin level was analyzed in studies by Kapur et al. (2013), 18 Diao et al. (2014), 20 Zeng et al. (2021), 26 Chishaki et al. (2021). 27 All cases were reported to have anemia, where the lowest level of hemoglobin was recorded by Zeng et al. (2021) decreased to 6.7 g/dl. 26 Discussion Hearing loss in patients with CML is a rare but serious complication that may be unilateral or bilateral or begin unilaterally and progress to bilateral sensorineural hearing loss. 1 , 30 Possible mechanisms of sudden hearing loss in CML are: hyperleukocytosis, hyper viscosity, infiltration of tumor cells into the cochlea, hemorrhagic and thrombotic manifestations, or infection. 31 , 32 Hyperleukocytosis is defined as a WBC >100 × 10 9 /L, while leukostasis occurs when leukocytes are above 300×10 9 /l. 6 In the studies of this review, the minimum WBC count recorded in hearing loss was 264 × 10 9 /L by Diao et al. (2014) and the maximum was 1343 × 10 9 /L by Ejele et al. (2013). 19 , 20 At the same time, in 69% of cases of CML and hearing loss, mean WBC values were in the range of 550–690 × 10 9 /L. This result is consistent with another reported value in which the likelihood of leukostasis is higher in patients with WBC levels above 150 × 10 9 /L. 1 Further findings from this review indicate that hyper viscosity leukocytosis is the primary cause of the coexistence of CML and hearing loss. 19 , 20 , 22 , 23 , 25 Thus, there is a strong correlation between WBC count and hearing loss, where WBC levels above 250 × 10 9 /L were associated with a high risk of ototoxicity, while levels above 500 × 10 9 /L were associated with higher risk of hearing loss. According to our research, patients with a WBC level of 150 × 10 9 /L may be at risk for ototoxicity and require treatment to reduce the likelihood that their condition would worsen. However, levels beyond 250×10 9 /L are highly likely to cause ototoxicity and require immediate care. Additionally, WBC levels of 500 × 10 9 /L and higher are certain indicators of ototoxicity, with a high risk of irreversibility in the event that hearing loss occurs. The authors of the included studies proposed a number of causes as the underlying pathological cause of sudden hearing loss. According to Tandon et al. (2021), rapid cochlear damage by hyperleukocytosis is the leading pathological cause of sudden hearing loss among six reported cases, consistent with previous studies. 28 , 33 Zeng et al. (2021) showed the presence of cochlear cellular ossification in patients with CML and persistent bilateral hearing loss. 26 Leukostasis and an inflammatory process ending in labyrinthitis explained the sudden hearing loss in CML reported by Aremu et al. 2018. 24 In addition, central hearing loss secondary to a hemorrhagic complication to the temporal and/or temporo-parietal lobe was another explanation by Alimam et al. (2013). 17 In CML, leukocytosis with an increase in blood viscosity in small vessels can result in rupture of the vascular layer and hemorrhage in the tissues, resulting in damage to the auditory complex, which leads to impaired projection of fibers from the medial geniculate bodies to the central auditory region, which ends in central hearing loss. 17 , 28 Thus, in the study by Kapur et al. (2013), the patient had sudden hearing loss due to intracranial hemorrhage in addition to an inflammatory process around the mastoid process. 18 A hypercoagulable state or blood clot formation due to hyper-viscosity is another possible mechanism for hearing loss in CML, and the risk of complications associated with hyper-viscosity in CML (such as priapism) is known. This is one part of the spectrum of patients who are diagnosed in the later stages of the disease, when they are already showing symptoms of very high WBC counts. 3 , 24 , 27 In the case report by Aremu et al. (2018), the patient had hearing loss due to hypodensity of the third and lateral ventricles, which was diagnosed using magnetic resonance imaging (MRI) of the brain. This was explained by occlusion of the vessels of the labyrinth and the vertebrobasilar region, leukocytosis and thrombus formation, which corresponded to the case described by Chishaki et al. (2021). 24 , 27 On the other hand, Sanyaolu et al. (2014) reported ten cases of local redness and inflammation in the tympanic membrane, highlighting the possibility of local leukemia cell infiltration as an etiological cause of hearing loss in leukemia cases, which was echoed in previous studies. 21 , 34 , 35 In addition, Yang 22 suggested that inner ear hemorrhage may be another rare cause of hearing loss in leukemia, requiring a special MRI study. 29 These assumptions and results support the evidence for a multifactorial etiology of hearing loss in cases of CML, with hyperleukocytosis and leukostasis being the primary causative agent. The study of the hearing loss manifestation patterns is another significant subject: about 84.6% of the included studies reported sudden bilateral onset of hearing loss. 17 – 19 , 22 – 26 , 28 , 29 In contrast, Diao et al. (2014) and Chishaki et al. (2021) found unilateral hearing loss as the main symptom, 20 , 27 with no clear correlation between bilateral hearing loss as a central cause. This indicates that both local otolaryngological and central radiographic examinations are necessary to assess hearing loss in systemic diseases, both in leukemia in general and in CML as such. In addition, due to the increased prevalence of the association, it has been recommended that all cases of CML be screened for hearing loss, even in asymptomatic cases. 21 , 36 Thus, Sanyaolu et al. (2014) studied otological diseases among 58 patients diagnosed with CML, the results of audiometry showed a higher prevalence of hearing disorders among 38 cases. The type of hearing loss onset in self-reported cases was sudden in 9 cases and in 7 hearing loss preceded the diagnosis of CML. Vertigo occurred in 4 of thirteen CML patients with self-reported hearing loss. 21 The authors concluded that this may reflect the high prevalence of otologic manifestations in cases of CML. 21 To some extent, this is consistent with a study by Joseph & Durosinmi (2008), who showed that of 33 cases of chronic myeloid leukemia, about 15% developed hearing loss. 37 However, there are no clear guidelines for screening, treatment, or follow-up of patients with CML with ototoxicity. Further results from this review showed that sudden hearing loss was the first clinical presentation of CML in 61.5% of the studies, 17 , 20 , 21 , 24 , 27 – 29 and in some cases shortly after the diagnosis of CML was made. 22 , 23 , 25 , 26 Therefore, hematologic malignancy, should be considered as a differential diagnosis in any case of acute sudden hearing loss. In fact, some cases studied have been reported in association with ocular toxicity (vision loss). 19 , 28 The latter, however, may be associated with hyperleukocytosis, stasis, and/or a hyper viscosity state that causes occlusion of retinal vessels, like vestibular ones, with further ischemic retinal injury, or due to increased intracranial pressure, retinal hemorrhage, or localized nerve infarction. 28 , 38 Nevertheless, in both studies by Ejele et al. (2013) and Tandon et al. (2021), there were no central hemorrhagic events or overt brain pathology, and the state of vision loss was reversible after treatment, in contrast to the hearing loss, which was permanent. 19 , 28 In terms of demographics such as age and gender, evidence suggests that the median age at diagnosis is 67 years and males are at higher risk for CML and mortality rates than females. 39 , 40 Similarly, consistent with evidence, males represented the majority (85%) of studied cases in this review. All female patients had irreversible hearing loss despite prompt, appropriate treatment, allowing to suggest gender (female) as an independent risk predictor of hearing loss in CML patients. 19 – 21 , 28 In addition, a distinct pattern was identified for the age of included cases. Thus, Alimam et al. (2013) reported a 100-year-old case, 17 while the overall analysis of the included studies showed that the cases were at a younger age (mean age 39.8 years) at diagnosis of CML and hearing loss. The management of CML cases depends on the phase in which the patients are. However, there have been certain approaches that have proven effective. Thus, a tyrosine kinase inhibitor (TKI) has been approved for the treatment of chronic phase CML (CP), although the use of TKI drugs (imatinib) may precipitate hearing loss. 41 , 42 However, this conclusion is highly controversial as further evidence has proven that neither imatinib nor nilotinib causes hearing loss after audiological screening and long follow-up. 43 , 44 Alas, this study can neither confirm nor refute the previous TKI controversy, as only one study by Tang et al. (2017) reported that the case was treated with unknown TKIs a few days before deafness, contradicting the imatinib ototoxicity theory that takes three months after starting treatment. 22 , 44 – 46 The management of CML in this review consisted of reduction of leukocytes using hydroxyurea as the primary treatment in all cases except Tandon et at. (2021), which started on imatinib as a first-line treatment. 28 However, there was no fixed treatment regimen for leukocytosis with sudden hearing loss in all of the cases studied. Patients were switched from hydroxyurea to imatinib after their leukocyte counts returned to normal. 17 – 21 , 23 , 26 , 27 Moreover, in the cases reported by Cass et at. (2018) and Chishaki et al. (2021) patients switched from hydroxyurea to dasatinib without reversible hearing loss. 23 , 27 In more detail, additive chemotherapy has been used as a cutting-edge treatment reported by Aremu et al. (2018), who used cyclophosphamide in addition to hydroxyurea, with favorable results in reversibility of hearing loss. 24 In addition, Tandon et al. (2021) found no clear benefit (in relation to hearing impairment) of adding a low dose of cytarabine 100 mg/day for 5 days to hydroxyurea (3 g/day) as an induction in two cases, consistent with previous data. 8 , 28 Despite the various approaches used to treat cases using single or combined drugs, the only reversibility of the hearing defect has been achieved after cochlear implantation. 18 , 22 , 26 One possible approach to improve outcomes could be early detection of CML cases with genetic mutation control and early active leukoreduction, which may prevent further complications such as sensorineural hearing loss. However, there is no clear guidance that combines the steps in the treatment of cases of CML with ototoxicity. This systematic literature review presented the available evidence and identifies gaps. Further research and recommendations are needed to explore the novel patterns and address the gaps. The study’s strength is its understudied topic, which could lead to recommendations and additional research on hearing loss and ototoxicity as early presentations in CML patients. Researching the prevalence of CML with ototoxicity as an upfront presentation in conjunction with audiology and ORL colleagues is suggested. From there, a strategic screen approach is developed for early diagnosis of CML by doing a basic CBC and referring patients to hematology anytime the disease is suspected. Another field of research is early leukoreduction, which aims to lower the WBC count to fewer than 200 in order to preserve the cochlear and audiology system. Furthermore, the absence of consistent audiological evaluation across studies is highlighting the necessity of more extensive investigations and illness management standards. Limitations This manuscript raises the important issue of hearing loss in CML. However, it may be considered biased in some cases because it is based almost entirely on case reports, which are themselves subject to bias. However, this was a unique attempt to compile the latest available literature, thereby showing what is known and where gaps exist, e.g., no age-adjusted data on the incidence of hearing loss in CML. This research will allow future researchers to make their case reports even more reliable and transparent. Although this systematic literature review has shed light on a number of previously under-researched issues in CML and hearing loss, it has some limitations that future researchers are recommended to address. First, only cases in adults are included; this may exclude additional significant data reported in the pediatric age group and should be highlighted in a separate article. The second limitation concerns the ten-year inclusion period. Several studies were published in the early 2000s and late 90s that may have changed our analysis and conclusions. On the other hand, some studies older than the last ten years are considered as an old reference, given the pace of development of certain health conditions and their management. The third limitation was the independent nature of the studies, which may contain some degree of error or bias as well as low evidence-based study as case report. Finally, retrospective data collection showed that some valuable measurements were missed, which could lead to a completely different outcome of this research. Conclusions Bilateral, irreversible hearing loss, primarily in middle-aged males, is a characteristic of the majority of published investigations on CML. Following vigorous treatment of CML, a visual and auditory impairment with a high degree of reversibility of ocular damage was seen in the majority of individuals. The reversibility of the hearing loss is not positively impacted by vigorous leukoreduction or leukapheresis, despite the fact that early treatment of CML may stop additional problems and the disease’s spread. Available case-based evidence suggests a potential association between high WBC counts and the risk of sudden hearing loss, warranting further investigation in larger, prospective studies. Ethics and consent Ethical approval and written consent were not required. Data availability statement No data are associated with this article. Underlying data Extended data Al-Ansari, Khadija et al. (Forthcoming 2024). Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [Dataset]. Dryad. https://doi.org/10.5061/dryad.ngf1vhj35 . This project contains the following underlying data: • Table 1. Characteristics of included studies (n = 13). • Table 2. JBI risk of bias quality assessment. • Table 3. Demographic and complete blood counts analysis in reported cases. Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication). Reporting guidelines The search and report process followed the statement and flowchart of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Supplemental information is being hosted by Zenodo: https://doi.org/10.5281/zenodo.12789792 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgment None to mention. References 1. Syamsuddin IK, Notopuro PB: Sensorineural Hearing Loss in Juvenile CML: A Rare Case Report in Surabaya, Indonesia. Int. Med. Case Rep. J. 2022; 15 : 367–371. PubMed Abstract | Publisher Full Text | Free Full Text 2. National Cancer Institute: Cancer Stat Facts: leukemia–chronic myeloid leukemia (CML).2018. [Accessed 2 nd June, 2023]. Reference Source 3. 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Janssen JJ, Berendse HW, Schuurhuis GJ, et al. : A 51-year-old male CML patient with progressive hearing loss, confusion, ataxia, and aphasia during imatinib treatment. Am. J. Hematol. 2009; 84 (10): 679–682. PubMed Abstract | Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 28 Aug 2024 ADD YOUR COMMENT Comment Author details Author details 1 Department of Otorhinolaryngology, King Hamad University Hospital, Muharaq, Bahrain 2 School of Health Sciences, School of Health Sciences, University of Salford, Manchester, England, UK 3 Department of Respiratory Therapy, Armed Forced Hospital, Najran, Saudi Arabia 4 Pediatric Intensive Care Unit, Pediatric Department, King Fahd Military Medical Complex, Dhahran, Saudi Arabia 5 Adult Hematology Unit, Internal Medicine Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia Khadija Al-Ansari Roles: Formal Analysis, Methodology Alexander Woodman Roles: Investigation, Validation, Writing – Review & Editing Lojin Mohammed Alghamdi Roles: Data Curation, Formal Analysis, Validation Turki Omaish Al otaibi Roles: Writing – Review & Editing Rehab Y. Al-Ansari Roles: Data Curation, Formal Analysis, Writing – Original Draft Preparation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 10 Sep 2025, 13:974 https://doi.org/10.12688/f1000research.151670.2 version 1 Published: 28 Aug 2024, 13:974 https://doi.org/10.12688/f1000research.151670.1 Copyright © 2025 Al-Ansari K et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Al-Ansari K, Woodman A, Mohammed Alghamdi L et al. Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] . F1000Research 2025, 13 :974 ( https://doi.org/10.12688/f1000research.151670.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 10 Sep 2025 Revised Views 0 Cite How to cite this report: Rinaldi I. Reviewer Report For: Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] . F1000Research 2025, 13 :974 ( https://doi.org/10.5256/f1000research.187822.r413126 ) The direct URL for this report is: https://f1000research.com/articles/13-974/v2#referee-response-413126 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 12 Sep 2025 Ikhwan Rinaldi , Cipto Mangunkusumo Hospital, Central Jakarta, Universitas Indonesia, Jakarta, Indonesia Approved VIEWS 0 https://doi.org/10.5256/f1000research.187822.r413126 Thank you for addressing the ... Continue reading READ ALL Thank you for addressing the revisions. I have no further comments. Competing Interests: No competing interests were disclosed. Reviewer Expertise: hemato-oncology, systematic review I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Rinaldi I. Reviewer Report For: Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] . F1000Research 2025, 13 :974 ( https://doi.org/10.5256/f1000research.187822.r413126 ) The direct URL for this report is: https://f1000research.com/articles/13-974/v2#referee-response-413126 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 28 Aug 2024 Views 0 Cite How to cite this report: Rinaldi I. Reviewer Report For: Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] . F1000Research 2025, 13 :974 ( https://doi.org/10.5256/f1000research.166332.r406838 ) The direct URL for this report is: https://f1000research.com/articles/13-974/v1#referee-response-406838 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 30 Aug 2025 Ikhwan Rinaldi , Cipto Mangunkusumo Hospital, Central Jakarta, Universitas Indonesia, Jakarta, Indonesia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.166332.r406838 The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is commendable. However, several important issues need to be addressed before the manuscript can be considered for ... Continue reading READ ALL The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is commendable. However, several important issues need to be addressed before the manuscript can be considered for indexing. Abstract The Methods section should briefly specify the types of studies included (case reports, case series, cross-sectional) and the critical appraisal tool used (JBI checklist). In the Results section, in addition to reporting percentages, please include key quantitative findings (e.g., mean WBC level associated with hearing loss, proportion of reversible vs irreversible cases) to improve informativeness. Methods Please provide more detail on how disagreements between reviewers during screening and data extraction were resolved. Since the majority of included studies are case reports, clarify how the JBI checklist was applied across different study designs. Results If possible, provide a clearer presentation of the JBI risk of bias assessment for each included study in table format. The term “irreversible” hearing loss should be defined more explicitly. Was irreversibility determined clinically, after specific treatments, or following a certain duration of follow-up? Discussion The discussion outlines potential mechanisms (hyperleukocytosis, leukostasis, infiltration, hemorrhage) but would benefit from a clearer linkage between reported WBC thresholds and clinical outcomes, supported by quantitative data. Please highlight both the strengths of the study and provide explicit recommendations for future research. Explicitly acknowledge the lack of standardized audiological evaluation across studies, as well as the predominance of case reports (low-level evidence), which may contribute to heterogeneity and limit generalizability. Expand on the potential for publication bias, since rare or severe presentations are more likely to be published. Conclusion The conclusion should be moderated to reflect the limitations of the evidence base (mostly case reports and small numbers). Instead of stating that “there is a strong correlation between WBC count and hearing loss,” consider rephrasing to: “Available case-based evidence suggests a potential association between high WBC counts and the risk of sudden hearing loss, warranting further investigation in larger, prospective studies.” Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? Partly If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: hemato-oncology, systematic review I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Rinaldi I. Reviewer Report For: Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] . F1000Research 2025, 13 :974 ( https://doi.org/10.5256/f1000research.166332.r406838 ) The direct URL for this report is: https://f1000research.com/articles/13-974/v1#referee-response-406838 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 11 Sep 2025 Rehab Al-Ansari , Adult Hematology Unit, Internal Medicine Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia 11 Sep 2025 Author Response Approved With Reservations The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is ... Continue reading Approved With Reservations The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is commendable. However, several important issues need to be addressed before the manuscript can be considered for indexing. Abstract The Methods section should briefly specify the types of studies included (case reports, case series, cross-sectional) and the critical appraisal tool used (JBI checklist). Dear Dr, Ikhwan Rinaldi, thanks for valuable review and comments. the abstract adjusted as per your recommendation. The appraisal tool further detail was mentioned in the subtitle under methodology title due to limitation of the words number under the abstract title. In the Results section, in addition to reporting percentages, please include key quantitative findings (e.g., mean WBC level associated with hearing loss, proportion of reversible vs irreversible cases) to improve informativeness. Thanks for valuable comments. The proportion of reversible vs irreversible cases is 1:10. And the mean WBC level associated with hearing loss was 554x10 9 /L. This was added to the result section under the abstract. Methods Please provide more detail on how disagreements between reviewers during screening and data extraction were resolved. Disagreements between reviewers were rarely happened during the screening and data extraction and no conflicts any level during or after the study . Since the majority of included studies are case reports, clarify how the JBI checklist was applied across different study designs. Thanks for the valid comment, due to in availability and missing of data around concerned topic, the case report was allowed to be used as a source of data, JBI checklist have variety of checklist for each study type, the checklist related to case report was used. https://jbi.global/critical-appraisal-tools Results If possible, provide a clearer presentation of the JBI risk of bias assessment for each included study in table format. Thanks for this comment, Table 2 added, ultimately re adjust previous Table 2 to Table 3. The term “irreversible” hearing loss should be defined more explicitly. Was irreversibility determined clinically, after specific treatments, or following a certain duration of follow-up? A. thanks for this valuable comment, An Irreversible hearing loss defines as persist ototoxic condition after medical or /and surgical treatments modality, with follow up after management for certain period of time. (This was added to the result section) Discussion The discussion outlines potential mechanisms (hyperleukocytosis, leukostasis, infiltration, hemorrhage) but would benefit from a clearer linkage between reported WBC thresholds and clinical outcomes, supported by quantitative data. Thanks for this comment. According to our research, patients with a WBC level of 150 × 10⁹/L may be at risk for ototoxicity and require treatment to reduce the likelihood that their condition would worsen. However, levels beyond 250×10⁹/L are highly likely to cause ototoxicity and require immediate care. Additionally, WBC levels of 500 × 10⁹/L and higher are certain indicators of ototoxicity, with a high risk of irreversibility in the event that hearing loss occurs. Please highlight both the strengths of the study and provide explicit recommendations for future research. Thanks for this guidance. The study's strength is its understudied topic, which could lead to recommendations and additional research on hearing loss and ototoxicity as early presentations in CML patients. Researching the prevalence of CML with ototoxicity as an upfront presentation in conjunction with audiology and ORL colleagues is suggested. From there, a strategic screen approach is developed for early diagnosis of CML by doing a basic CBC and referring patients to hematology anytime the disease is suspected. Another field of research is early leukoreduction, which aims to lower the WBC count to fewer than 200 in order to preserve the cochlear and audiology system. (this was added to the discussion section prior to limitation) Explicitly acknowledge the lack of standardized audiological evaluation across studies, as well as the predominance of case reports (low-level evidence), which may contribute to heterogeneity and limit generalizability. A. Thanks for this comment. This has been added to the limitation section and is considered a limitation. Additionally, the absence of consistent audiological evaluation across studies is highlighting the necessity of more extensive investigations and illness management standards. Expand on the potential for publication bias, since rare or severe presentations are more likely to be published. . Thank you for the valuable comment. Conclusion The conclusion should be moderated to reflect the limitations of the evidence base (mostly case reports and small numbers). Instead of stating that “there is a strong correlation between WBC count and hearing loss,” consider rephrasing to: “Available case-based evidence suggests a potential association between high WBC counts and the risk of sudden hearing loss, warranting further investigation in larger, prospective studies.” A. thanks for your valuable comment, the conclusion re written based on your kind recommendation. Approved With Reservations The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is commendable. However, several important issues need to be addressed before the manuscript can be considered for indexing. Abstract The Methods section should briefly specify the types of studies included (case reports, case series, cross-sectional) and the critical appraisal tool used (JBI checklist). Dear Dr, Ikhwan Rinaldi, thanks for valuable review and comments. the abstract adjusted as per your recommendation. The appraisal tool further detail was mentioned in the subtitle under methodology title due to limitation of the words number under the abstract title. In the Results section, in addition to reporting percentages, please include key quantitative findings (e.g., mean WBC level associated with hearing loss, proportion of reversible vs irreversible cases) to improve informativeness. Thanks for valuable comments. The proportion of reversible vs irreversible cases is 1:10. And the mean WBC level associated with hearing loss was 554x10 9 /L. This was added to the result section under the abstract. Methods Please provide more detail on how disagreements between reviewers during screening and data extraction were resolved. Disagreements between reviewers were rarely happened during the screening and data extraction and no conflicts any level during or after the study . Since the majority of included studies are case reports, clarify how the JBI checklist was applied across different study designs. Thanks for the valid comment, due to in availability and missing of data around concerned topic, the case report was allowed to be used as a source of data, JBI checklist have variety of checklist for each study type, the checklist related to case report was used. https://jbi.global/critical-appraisal-tools Results If possible, provide a clearer presentation of the JBI risk of bias assessment for each included study in table format. Thanks for this comment, Table 2 added, ultimately re adjust previous Table 2 to Table 3. The term “irreversible” hearing loss should be defined more explicitly. Was irreversibility determined clinically, after specific treatments, or following a certain duration of follow-up? A. thanks for this valuable comment, An Irreversible hearing loss defines as persist ototoxic condition after medical or /and surgical treatments modality, with follow up after management for certain period of time. (This was added to the result section) Discussion The discussion outlines potential mechanisms (hyperleukocytosis, leukostasis, infiltration, hemorrhage) but would benefit from a clearer linkage between reported WBC thresholds and clinical outcomes, supported by quantitative data. Thanks for this comment. According to our research, patients with a WBC level of 150 × 10⁹/L may be at risk for ototoxicity and require treatment to reduce the likelihood that their condition would worsen. However, levels beyond 250×10⁹/L are highly likely to cause ototoxicity and require immediate care. Additionally, WBC levels of 500 × 10⁹/L and higher are certain indicators of ototoxicity, with a high risk of irreversibility in the event that hearing loss occurs. Please highlight both the strengths of the study and provide explicit recommendations for future research. Thanks for this guidance. The study's strength is its understudied topic, which could lead to recommendations and additional research on hearing loss and ototoxicity as early presentations in CML patients. Researching the prevalence of CML with ototoxicity as an upfront presentation in conjunction with audiology and ORL colleagues is suggested. From there, a strategic screen approach is developed for early diagnosis of CML by doing a basic CBC and referring patients to hematology anytime the disease is suspected. Another field of research is early leukoreduction, which aims to lower the WBC count to fewer than 200 in order to preserve the cochlear and audiology system. (this was added to the discussion section prior to limitation) Explicitly acknowledge the lack of standardized audiological evaluation across studies, as well as the predominance of case reports (low-level evidence), which may contribute to heterogeneity and limit generalizability. A. Thanks for this comment. This has been added to the limitation section and is considered a limitation. Additionally, the absence of consistent audiological evaluation across studies is highlighting the necessity of more extensive investigations and illness management standards. Expand on the potential for publication bias, since rare or severe presentations are more likely to be published. . Thank you for the valuable comment. Conclusion The conclusion should be moderated to reflect the limitations of the evidence base (mostly case reports and small numbers). Instead of stating that “there is a strong correlation between WBC count and hearing loss,” consider rephrasing to: “Available case-based evidence suggests a potential association between high WBC counts and the risk of sudden hearing loss, warranting further investigation in larger, prospective studies.” A. thanks for your valuable comment, the conclusion re written based on your kind recommendation. Competing Interests: we disclosed that there is no competing on interest Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 11 Sep 2025 Rehab Al-Ansari , Adult Hematology Unit, Internal Medicine Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia 11 Sep 2025 Author Response Approved With Reservations The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is ... Continue reading Approved With Reservations The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is commendable. However, several important issues need to be addressed before the manuscript can be considered for indexing. Abstract The Methods section should briefly specify the types of studies included (case reports, case series, cross-sectional) and the critical appraisal tool used (JBI checklist). Dear Dr, Ikhwan Rinaldi, thanks for valuable review and comments. the abstract adjusted as per your recommendation. The appraisal tool further detail was mentioned in the subtitle under methodology title due to limitation of the words number under the abstract title. In the Results section, in addition to reporting percentages, please include key quantitative findings (e.g., mean WBC level associated with hearing loss, proportion of reversible vs irreversible cases) to improve informativeness. Thanks for valuable comments. The proportion of reversible vs irreversible cases is 1:10. And the mean WBC level associated with hearing loss was 554x10 9 /L. This was added to the result section under the abstract. Methods Please provide more detail on how disagreements between reviewers during screening and data extraction were resolved. Disagreements between reviewers were rarely happened during the screening and data extraction and no conflicts any level during or after the study . Since the majority of included studies are case reports, clarify how the JBI checklist was applied across different study designs. Thanks for the valid comment, due to in availability and missing of data around concerned topic, the case report was allowed to be used as a source of data, JBI checklist have variety of checklist for each study type, the checklist related to case report was used. https://jbi.global/critical-appraisal-tools Results If possible, provide a clearer presentation of the JBI risk of bias assessment for each included study in table format. Thanks for this comment, Table 2 added, ultimately re adjust previous Table 2 to Table 3. The term “irreversible” hearing loss should be defined more explicitly. Was irreversibility determined clinically, after specific treatments, or following a certain duration of follow-up? A. thanks for this valuable comment, An Irreversible hearing loss defines as persist ototoxic condition after medical or /and surgical treatments modality, with follow up after management for certain period of time. (This was added to the result section) Discussion The discussion outlines potential mechanisms (hyperleukocytosis, leukostasis, infiltration, hemorrhage) but would benefit from a clearer linkage between reported WBC thresholds and clinical outcomes, supported by quantitative data. Thanks for this comment. According to our research, patients with a WBC level of 150 × 10⁹/L may be at risk for ototoxicity and require treatment to reduce the likelihood that their condition would worsen. However, levels beyond 250×10⁹/L are highly likely to cause ototoxicity and require immediate care. Additionally, WBC levels of 500 × 10⁹/L and higher are certain indicators of ototoxicity, with a high risk of irreversibility in the event that hearing loss occurs. Please highlight both the strengths of the study and provide explicit recommendations for future research. Thanks for this guidance. The study's strength is its understudied topic, which could lead to recommendations and additional research on hearing loss and ototoxicity as early presentations in CML patients. Researching the prevalence of CML with ototoxicity as an upfront presentation in conjunction with audiology and ORL colleagues is suggested. From there, a strategic screen approach is developed for early diagnosis of CML by doing a basic CBC and referring patients to hematology anytime the disease is suspected. Another field of research is early leukoreduction, which aims to lower the WBC count to fewer than 200 in order to preserve the cochlear and audiology system. (this was added to the discussion section prior to limitation) Explicitly acknowledge the lack of standardized audiological evaluation across studies, as well as the predominance of case reports (low-level evidence), which may contribute to heterogeneity and limit generalizability. A. Thanks for this comment. This has been added to the limitation section and is considered a limitation. Additionally, the absence of consistent audiological evaluation across studies is highlighting the necessity of more extensive investigations and illness management standards. Expand on the potential for publication bias, since rare or severe presentations are more likely to be published. . Thank you for the valuable comment. Conclusion The conclusion should be moderated to reflect the limitations of the evidence base (mostly case reports and small numbers). Instead of stating that “there is a strong correlation between WBC count and hearing loss,” consider rephrasing to: “Available case-based evidence suggests a potential association between high WBC counts and the risk of sudden hearing loss, warranting further investigation in larger, prospective studies.” A. thanks for your valuable comment, the conclusion re written based on your kind recommendation. Approved With Reservations The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is commendable. However, several important issues need to be addressed before the manuscript can be considered for indexing. Abstract The Methods section should briefly specify the types of studies included (case reports, case series, cross-sectional) and the critical appraisal tool used (JBI checklist). Dear Dr, Ikhwan Rinaldi, thanks for valuable review and comments. the abstract adjusted as per your recommendation. The appraisal tool further detail was mentioned in the subtitle under methodology title due to limitation of the words number under the abstract title. In the Results section, in addition to reporting percentages, please include key quantitative findings (e.g., mean WBC level associated with hearing loss, proportion of reversible vs irreversible cases) to improve informativeness. Thanks for valuable comments. The proportion of reversible vs irreversible cases is 1:10. And the mean WBC level associated with hearing loss was 554x10 9 /L. This was added to the result section under the abstract. Methods Please provide more detail on how disagreements between reviewers during screening and data extraction were resolved. Disagreements between reviewers were rarely happened during the screening and data extraction and no conflicts any level during or after the study . Since the majority of included studies are case reports, clarify how the JBI checklist was applied across different study designs. Thanks for the valid comment, due to in availability and missing of data around concerned topic, the case report was allowed to be used as a source of data, JBI checklist have variety of checklist for each study type, the checklist related to case report was used. https://jbi.global/critical-appraisal-tools Results If possible, provide a clearer presentation of the JBI risk of bias assessment for each included study in table format. Thanks for this comment, Table 2 added, ultimately re adjust previous Table 2 to Table 3. The term “irreversible” hearing loss should be defined more explicitly. Was irreversibility determined clinically, after specific treatments, or following a certain duration of follow-up? A. thanks for this valuable comment, An Irreversible hearing loss defines as persist ototoxic condition after medical or /and surgical treatments modality, with follow up after management for certain period of time. (This was added to the result section) Discussion The discussion outlines potential mechanisms (hyperleukocytosis, leukostasis, infiltration, hemorrhage) but would benefit from a clearer linkage between reported WBC thresholds and clinical outcomes, supported by quantitative data. Thanks for this comment. According to our research, patients with a WBC level of 150 × 10⁹/L may be at risk for ototoxicity and require treatment to reduce the likelihood that their condition would worsen. However, levels beyond 250×10⁹/L are highly likely to cause ototoxicity and require immediate care. Additionally, WBC levels of 500 × 10⁹/L and higher are certain indicators of ototoxicity, with a high risk of irreversibility in the event that hearing loss occurs. Please highlight both the strengths of the study and provide explicit recommendations for future research. Thanks for this guidance. The study's strength is its understudied topic, which could lead to recommendations and additional research on hearing loss and ototoxicity as early presentations in CML patients. Researching the prevalence of CML with ototoxicity as an upfront presentation in conjunction with audiology and ORL colleagues is suggested. From there, a strategic screen approach is developed for early diagnosis of CML by doing a basic CBC and referring patients to hematology anytime the disease is suspected. Another field of research is early leukoreduction, which aims to lower the WBC count to fewer than 200 in order to preserve the cochlear and audiology system. (this was added to the discussion section prior to limitation) Explicitly acknowledge the lack of standardized audiological evaluation across studies, as well as the predominance of case reports (low-level evidence), which may contribute to heterogeneity and limit generalizability. A. Thanks for this comment. This has been added to the limitation section and is considered a limitation. Additionally, the absence of consistent audiological evaluation across studies is highlighting the necessity of more extensive investigations and illness management standards. Expand on the potential for publication bias, since rare or severe presentations are more likely to be published. . Thank you for the valuable comment. Conclusion The conclusion should be moderated to reflect the limitations of the evidence base (mostly case reports and small numbers). Instead of stating that “there is a strong correlation between WBC count and hearing loss,” consider rephrasing to: “Available case-based evidence suggests a potential association between high WBC counts and the risk of sudden hearing loss, warranting further investigation in larger, prospective studies.” A. thanks for your valuable comment, the conclusion re written based on your kind recommendation. Competing Interests: we disclosed that there is no competing on interest Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 28 Aug 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 Version 2 (revision) 10 Sep 25 read Version 1 28 Aug 24 read Ikhwan Rinaldi , Universitas Indonesia, Jakarta, Indonesia Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Rinaldi I. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 12 Sep 2025 | for Version 2 Ikhwan Rinaldi , Cipto Mangunkusumo Hospital, Central Jakarta, Universitas Indonesia, Jakarta, Indonesia 0 Views copyright © 2025 Rinaldi I. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Thank you for addressing the revisions. I have no further comments. Competing Interests No competing interests were disclosed. Reviewer Expertise hemato-oncology, systematic review I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Rinaldi I. Peer Review Report For: Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] . F1000Research 2025, 13 :974 ( https://doi.org/10.5256/f1000research.187822.r413126) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-974/v2#referee-response-413126 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Rinaldi I. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 30 Aug 2025 | for Version 1 Ikhwan Rinaldi , Cipto Mangunkusumo Hospital, Central Jakarta, Universitas Indonesia, Jakarta, Indonesia 0 Views copyright © 2025 Rinaldi I. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is commendable. However, several important issues need to be addressed before the manuscript can be considered for indexing. Abstract The Methods section should briefly specify the types of studies included (case reports, case series, cross-sectional) and the critical appraisal tool used (JBI checklist). In the Results section, in addition to reporting percentages, please include key quantitative findings (e.g., mean WBC level associated with hearing loss, proportion of reversible vs irreversible cases) to improve informativeness. Methods Please provide more detail on how disagreements between reviewers during screening and data extraction were resolved. Since the majority of included studies are case reports, clarify how the JBI checklist was applied across different study designs. Results If possible, provide a clearer presentation of the JBI risk of bias assessment for each included study in table format. The term “irreversible” hearing loss should be defined more explicitly. Was irreversibility determined clinically, after specific treatments, or following a certain duration of follow-up? Discussion The discussion outlines potential mechanisms (hyperleukocytosis, leukostasis, infiltration, hemorrhage) but would benefit from a clearer linkage between reported WBC thresholds and clinical outcomes, supported by quantitative data. Please highlight both the strengths of the study and provide explicit recommendations for future research. Explicitly acknowledge the lack of standardized audiological evaluation across studies, as well as the predominance of case reports (low-level evidence), which may contribute to heterogeneity and limit generalizability. Expand on the potential for publication bias, since rare or severe presentations are more likely to be published. Conclusion The conclusion should be moderated to reflect the limitations of the evidence base (mostly case reports and small numbers). Instead of stating that “there is a strong correlation between WBC count and hearing loss,” consider rephrasing to: “Available case-based evidence suggests a potential association between high WBC counts and the risk of sudden hearing loss, warranting further investigation in larger, prospective studies.” Are the rationale for, and objectives of, the Systematic Review clearly stated? Yes Are sufficient details of the methods and analysis provided to allow replication by others? Yes Is the statistical analysis and its interpretation appropriate? Not applicable Are the conclusions drawn adequately supported by the results presented in the review? Partly If this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise hemato-oncology, systematic review I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 11 Sep 2025 Rehab Al-Ansari, Adult Hematology Unit, Internal Medicine Department, King Fahad Military Medical Complex, Dhahran, Saudi Arabia Approved With Reservations The manuscript addresses a rare but clinically interesting topic concerning the coexistence of hearing loss and chronic myeloid leukemia (CML). The systematic approach is commendable. However, several important issues need to be addressed before the manuscript can be considered for indexing. Abstract The Methods section should briefly specify the types of studies included (case reports, case series, cross-sectional) and the critical appraisal tool used (JBI checklist). Dear Dr, Ikhwan Rinaldi, thanks for valuable review and comments. the abstract adjusted as per your recommendation. The appraisal tool further detail was mentioned in the subtitle under methodology title due to limitation of the words number under the abstract title. In the Results section, in addition to reporting percentages, please include key quantitative findings (e.g., mean WBC level associated with hearing loss, proportion of reversible vs irreversible cases) to improve informativeness. Thanks for valuable comments. The proportion of reversible vs irreversible cases is 1:10. And the mean WBC level associated with hearing loss was 554x10 9 /L. This was added to the result section under the abstract. Methods Please provide more detail on how disagreements between reviewers during screening and data extraction were resolved. Disagreements between reviewers were rarely happened during the screening and data extraction and no conflicts any level during or after the study . Since the majority of included studies are case reports, clarify how the JBI checklist was applied across different study designs. Thanks for the valid comment, due to in availability and missing of data around concerned topic, the case report was allowed to be used as a source of data, JBI checklist have variety of checklist for each study type, the checklist related to case report was used. https://jbi.global/critical-appraisal-tools Results If possible, provide a clearer presentation of the JBI risk of bias assessment for each included study in table format. Thanks for this comment, Table 2 added, ultimately re adjust previous Table 2 to Table 3. The term “irreversible” hearing loss should be defined more explicitly. Was irreversibility determined clinically, after specific treatments, or following a certain duration of follow-up? A. thanks for this valuable comment, An Irreversible hearing loss defines as persist ototoxic condition after medical or /and surgical treatments modality, with follow up after management for certain period of time. (This was added to the result section) Discussion The discussion outlines potential mechanisms (hyperleukocytosis, leukostasis, infiltration, hemorrhage) but would benefit from a clearer linkage between reported WBC thresholds and clinical outcomes, supported by quantitative data. Thanks for this comment. According to our research, patients with a WBC level of 150 × 10⁹/L may be at risk for ototoxicity and require treatment to reduce the likelihood that their condition would worsen. However, levels beyond 250×10⁹/L are highly likely to cause ototoxicity and require immediate care. Additionally, WBC levels of 500 × 10⁹/L and higher are certain indicators of ototoxicity, with a high risk of irreversibility in the event that hearing loss occurs. Please highlight both the strengths of the study and provide explicit recommendations for future research. Thanks for this guidance. The study's strength is its understudied topic, which could lead to recommendations and additional research on hearing loss and ototoxicity as early presentations in CML patients. Researching the prevalence of CML with ototoxicity as an upfront presentation in conjunction with audiology and ORL colleagues is suggested. From there, a strategic screen approach is developed for early diagnosis of CML by doing a basic CBC and referring patients to hematology anytime the disease is suspected. Another field of research is early leukoreduction, which aims to lower the WBC count to fewer than 200 in order to preserve the cochlear and audiology system. (this was added to the discussion section prior to limitation) Explicitly acknowledge the lack of standardized audiological evaluation across studies, as well as the predominance of case reports (low-level evidence), which may contribute to heterogeneity and limit generalizability. A. Thanks for this comment. This has been added to the limitation section and is considered a limitation. Additionally, the absence of consistent audiological evaluation across studies is highlighting the necessity of more extensive investigations and illness management standards. Expand on the potential for publication bias, since rare or severe presentations are more likely to be published. . Thank you for the valuable comment. Conclusion The conclusion should be moderated to reflect the limitations of the evidence base (mostly case reports and small numbers). Instead of stating that “there is a strong correlation between WBC count and hearing loss,” consider rephrasing to: “Available case-based evidence suggests a potential association between high WBC counts and the risk of sudden hearing loss, warranting further investigation in larger, prospective studies.” A. thanks for your valuable comment, the conclusion re written based on your kind recommendation. View more View less Competing Interests we disclosed that there is no competing on interest reply Respond Report a concern Rinaldi I. Peer Review Report For: Coexisting of hearing loss and chronic myeloid leukemia - A systematic literature review [version 2; peer review: 1 approved] . F1000Research 2025, 13 :974 ( https://doi.org/10.5256/f1000research.166332.r406838) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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