-->PONE-D-26-09272-->-->Diagnostic Accuracy of Automated Hematology Analyzer Abnormal Flags for Detecting Hematological Malignancies: A Systematic Review and Meta-Analysis-->-->PLOS One

Dear Dr. Mulatie,

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ACADEMIC EDITOR:  Major revision

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Academic Editor

PLOS One

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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-->2. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: No

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-->5. Review Comments to the Author

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Reviewer #1: This manuscript addresses a clinically relevant question regarding the diagnostic utility of abnormal hematology analyzer flags for hematological malignancies. The study has potential value, particularly for laboratories in resource-limited settings where automated screening tools may support early case identification and improve laboratory workflow.

The manuscript includes several strengths, including use of standard diagnostic meta-analysis techniques, subgroup analyses, and clinical utility assessments. However, substantial revisions are required before the manuscript can meet the methodological and reporting standards expected for publication in PLOS ONE.

The major concerns include:

extremely high heterogeneity,

pooling of clinically heterogeneous conditions and flag types,

inconsistent reference standards,

possible non-independence of datasets,

insufficient methodological transparency,

and overinterpretation of pooled findings.

In addition, the manuscript requires substantial language editing and restructuring of the discussion section to reduce repetition and improve analytical depth.

Reviewer #2: This systematic review and meta-analysis addresses an important and clinically relevant topic. The evaluation of automated hematology analyzer abnormal flags for the detection of hematological malignancies is of practical significance, particularly in settings where rapid and cost-effective screening tools are needed. The manuscript is generally well organized, and the authors have applied recognized methods for diagnostic test accuracy meta-analysis.

However, several issues should be addressed before the manuscript can be considered for publication.

Major comments

1. The search strategy requires clarification. The supplementary search strategy includes a randomized controlled trial filter in PubMed despite the review focusing on diagnostic accuracy studies. The rationale for this approach should be explained, and the authors should discuss whether relevant studies may have been inadvertently excluded. In addition, the search syntax contains several formatting inconsistencies and should be presented in a fully reproducible manner.

2. The pooled analyses demonstrate extremely high heterogeneity for both sensitivity and specificity. Although subgroup analyses and meta-regression were performed, the manuscript would benefit from a more detailed discussion of the sources of heterogeneity and their implications for interpretation of the pooled estimates.

3. Several publications contributed multiple datasets to the meta-analysis. The authors should clarify how these datasets were handled statistically and discuss any potential impact on the pooled results.

4. The included studies used different reference standards, including microscopy, flow cytometry, bone marrow examination, and combined approaches. The potential influence of this variability on diagnostic accuracy estimates should be discussed more thoroughly.

5. The conclusions should be moderated to emphasize that abnormal analyzer flags are useful screening tools but cannot replace confirmatory diagnostic methods such as peripheral blood smear review, flow cytometry, or bone marrow examination.

Minor comments

1. The manuscript requires substantial English-language editing. Numerous grammatical errors, typographical errors, and awkward sentence constructions are present throughout the text.

2. Terminology should be standardized throughout the manuscript to improve clarity and consistency.

3. Table 1 would benefit from improved formatting and clearer presentation of multiple datasets originating from the same publication.

Overall, this study addresses an important topic and has the potential to make a useful contribution to the field. However, the methodological and reporting issues outlined above should be addressed before the manuscript is considered for publication.

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Reviewer #1: Yes:  GYESI RAZAK ISSAHAKU

Reviewer #2: No

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Diagnostic Accuracy of Automated Hematology Analyzer Abnormal Flags for Detecting Hematological Malignancies: A Systematic Review and Meta-Analysis

PONE-D-26-09272R1

Dear Dr. Zewudu Mulatie,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Marwan Salih Al-Nimer, MD, PhD

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments: