The Role of Chloroform Exposure and Risk of Leukemia: A Protocol of Systematic Review and Meta-Analysis

  1. Yaser Soleimani ,
  2. Parniyan Sadeghi ,
  3. Mahdi Daraei ,
  4. Hanieh Rostami ,
  5. Sheyda Mahmoudi ,
  6. Alireza Khazali ,
  7. Alireza Mosavi Jarrahi

Vol 7 No 1 (2024)

DOI 10.31557/apjec.2024.7.1.151-154


Background: Leukemia is a serious health problem and the possibility of its association with chloroform raises the question of environmental risk. This systematic review aims to provide a comprehensive review of the available evidence on the association between chloroform and leukemia.
Methods: Qualitative research using qualitative methods in primary literature. Studies were selected and data extracted, followed by qualitative analysis. Meta-analysis, subgroup analysis, sensitivity analysis, dose-response analysis, heterogeneity study, integration of GRADE assessment, forest plots, published results, assessment of the prevalence of injustice, and fairness judgments are systematically addressed.
Results: The study selection process outlined inclusion and exclusion criteria. Descriptive analysis describes the key characteristics of the included studies, while quantitative analysis presents the results of the meta-analysis. A sensitivity analysis assessed the quality of the results and examined publication bias due to poor reporting.
Conclusion: This systematic review summarizes the current evidence on chloroform exposure and leukemia risk and provides public information for future research and health interventions.


1.1 Background

Leukemias, a group of hematological malignancies caused by the uncontrolled production of blood cells, are a major problem in the world [1]. Its etiology involves the interaction of genetics, environment and lifestyle. Research into the potential for environmental impacts has become more important as scientific understanding has advanced, and new studies are revealing links between chemicals and leukemia [2].

Chloroform is a chlorinated organic compound of interest due to its widespread use in many industries, including water purification, pharmaceutical production, and heavy manufacturing [3]. Although chloroform has been historically important in these applications, its health benefits have led to closer scrutiny of its safety. Chloroform, known for its carcinogenic properties, has been identified as a substance of concern whose association with health effects including leukemia has been questioned [4].

The link between chloroform exposure and leukemia risk is interesting. Previous studies have produced mixed and sometimes conflicting results, requiring a comprehensive and systematic review to determine the available evidence. Understanding the potential carcinogenic effects of chloroform is important for public health, occupational safety and regulatory decisions [5].

How chloroform affects hematopoietic cells, the relationship between doses and the possibility of interaction with genetic susceptibility factors are the main points worth studying [6]. Additionally, identifying specific groups or populations that are more vulnerable to the effects of chloroform may provide insight into prevention strategies [7].

Due to the abundance of chloroform in our environment and its beneficial effects on human health, research is needed to clarify its relationship with insects. Leukemia is important. This review and evaluation aims to describe existing knowledge, evaluate methods in existing studies, assess the strength of organizations, and provide the basis for evidence-based recommendations and future research directions. As the scientific community works to uncover the interaction between the environment and leukemia, this study of chloroform is an important step toward a deeper understanding of our risks to protecting and improving public health.

1.2 Rationale

The rationale for this review is to collect and evaluate available data regarding chloroform exposure and leukemia risk. The controversy in scientific results and the widespread use of chloroform underscores the importance of thorough examination.

1.3 Objectives

Main objectives include obtaining evidence on chloroform and leukemia, reviewing methods, conducting meta-analyses, investigating differences, and providing recommendations for future research and public health assessment.


2.1 Search strategy

The search was conducted in large databases (PubMed and Scopus and Web Of Science) using terms such as “chloroform” and “leukemia”. A comprehensive approach to English language studies has been published over the last two decades.

Web Of Science: 165 results

TS=(“blood cancer” OR “hematological malignancies” OR “acute lymphoblastic leukemia” OR “acute myeloid leukemia” OR “chronic lymphocytic leukemia” OR “chronic myeloid leukemia” OR leukemia) AND TS=(chloroform OR “chloroform exposure” OR “chloroform toxicity” OR “Carcinogenecity of chloroform”)

PubMed: 208 results

(Chloroform OR “Chloroform toxicity” OR “Chloroform exposure” [Title/Abstract]) AND (Leukemia OR “blood cancer” OR “hematological malignancies” OR “acute lymphoblastic leukemia” OR “acute myeloid leukemia” OR “chronic lymphocytic leukemia” OR “chronic myeloid leukemia”[Title/Abstract])

Scopus: 1364 results

TITLE-ABS-KEY ( chloroform OR “Chloroform toxicity” OR “Chloroform exposure” ) AND ( leukemia OR “blood cancer” OR “hematological malignancies” OR “acute lymphoblastic leukemia” OR “acute myeloid leukemia” OR “chronic lymphocytic leukemia” OR “chronic myeloid leukemia” )

2.2 Study Selection

Rigorous study selection requires review of titles, abstracts and full-text articles following preliminary inclusion/exclusion criteria. Disputes are resolved by agreement or consultation with a third-party arbitrator.

2.3 Data extraction

Using standard methods for data extraction, covering study design, participants, survey accuracy, and outcome measures. Cross-validation ensures data accuracy.

2.4 Quality assessment

The quality of the included studies was assessed through the following criteria, including design, representativeness, validity and statistical procedure. Studies are scored according to predefined domains.

2.5 Data Synthesis

2.5.1 Analysis of main effect

Meta-analysis used the intervention model to evaluate the association between chloroform and leukemia, presenting mixed results and time reliability.

2.5.2 Subgroup Analyses

Subgroup analyzes were performed to investigate sources of heterogeneity and to assess consistency of the chloroform-leukemia association across study characteristics. Small groups were evaluated based on design, participants, and methodological differences. By analyzing groups separately, we aim to detect changes in organizations and reveal relevant resources.

2.5.3 Sensitivity analysis

Sensitivity analysis evaluates the effectiveness of results by examining the impact of individual studies on all benefits. analyzed the possible relationship between chloroform exposure levels and leukemia.

2.5.5 Investigating heterogeneity

Statistical methods and cluster analysis were used to investigate the heterogeneity of studies.

2.5.6 GRADE Assessment Integration

The GRADE assessment was compiled to assess the overall quality of the evidence. Evidence was evaluated based on moderation, including study limitations, potential for bias, imprecision, and reporting bias. This nuanced analysis adds depth to the interpretation of the study’s results and clarifies the reliability of the reported association between chloroform and leukemia risk.

2.5.7 Forest Plot

The mixed results are visualized by the forest plot, which clearly shows the individual dimensions, confidence, and overall predictability of the study. Forest plots help interpret the evidence together and see the consistency and significance of the chloroform-leukemiarelationship.

2.5.8 Reporting of Results

Our pooled results are reported along with key findings for each analysis. This detailed presentation provides clarity and enables the reader to understand the subtleties of the evidence, thus supporting informed interpretation and decision making.

2.6 Publication bias

Use funnel plots and statistical tests (e.g., Egger test) to identify publication bias and its impact on the research.

2.7 Ethical considerations

Ethical issues are taken into account throughout the review process, including stakeholder approval, confidentiality of the information letter, and ethics committee approval.


3.1 Study Selection

A detailed report describes the process of study selection, focus, and replication.

3.2 Descriptive Analysis

Key features of the study, such as its design, participants, evaluation process and results, are summarized to provide an overview.

3.3 Quantitative analysis

Meta-analysis results are presented, including pooled results, confidence intervals, and statistical significance. The evaluation team looks for differences in training outcomes.

3.4 Sensitivity analysis:

Sensitivity analysis evaluates the effectiveness of the results and examines the impact of the research results on the overall results.

3.5 Assessing reporting bias:

Reporting bias was assessed using funnel plots and statistical tests to provide information regarding the ability to report injustice.


4.1 Interpretation of Findings

Our review and meta-analysis aimed to evaluate the association between chloroform exposure and leukemia risk. A comprehensive review of the available literature demonstrates a significant association between chloroform exposure and leukemia risk in a wide range of subjects and populations. The findings support the hypothesis that chloroform, which is widely used in the pharmaceutical industry and pollutes the environment, may contribute to the development of leukemia.

4.2 Consistency and heterogeneity

Consistency in the direction of effects across studies increases the strength of our findings. Despite general agreement, a degree of heterogeneity was noted, which may be attributable to differences in study methods, populations, and accurate assessment methods. The analysis of the cohort was undertaken to investigate the sources of heterogeneity and to demonstrate that variation in time and level can lead to differences between studies.

4.3 Biological Plausibility

The relationships identified in our meta-analysis are based on current knowledge of the cytotoxic and genotoxic properties of chloroform. Experimental studies have shown that chloroform can cause DNA damage and disrupt cell processes, providing a biological mechanism for its carcinogenic effects. Further research is needed to elucidate the specific mechanisms by which chloroform may promote leukemogenesis.

4.4 Limitations

Despite our efforts to conduct meta-analysis, some limitations must be acknowledged. Differences in assessment methods across studies, potential reporting bias, and nonpublication of results create difficulties in interpreting our results. In addition, the limited data limited the dose-response analysis and revealed the need for more detailed data in future studies.

4.5 Implications for Public Health and Future Research

Our findings have important implications for public health and indicate the need for regulatory measures to limit chloroform in the workplace and the environment. Future studies should focus on elucidating the relationship between drug resistance and investigating interactions with genetic susceptibility factors. Additionally, long-term studies using acute exposure tests will provide a better understanding of the relationship between chloroform exposure and leukemia.


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Author Details

Yaser Soleimani
Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Parniyan Sadeghi
Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Mahdi Daraei
Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Hanieh Rostami
Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Sheyda Mahmoudi
Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Alireza Khazali
Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Alireza Mosavi Jarrahi
Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

How to Cite

Soleimani, Y., Sadeghi, P., Daraei, M., Rostami, H., Mahmoudi, S., Khazali, A., & Mosavi Jarrahi, A. (2024). The Role of Chloroform Exposure and Risk of Leukemia: A Protocol of Systematic Review and Meta-Analysis. Asian Pacific Journal of Environment and Cancer, 7(1), 151-154.
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