The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysis

Dina Garniasih; Susi Susanah; Yunia Sribudiani; Dany Hilmanto

doi:10.1371/journal.pone.0269706

Peer Review History

Original SubmissionApril 6, 2022
1 May 2022 Decision Letter - Mohamed A Yassin, Editor PONE-D-22-09885The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysisPLOS ONE Dear Dr. Dina, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ACADEMIC EDITOR: Please insert comments here and delete this placeholder text when finished. Be sure to: The manuscript needs revision please check reviewers comments and address accordingly Please submit your revised manuscript by Jun 15 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Mohamed A Yassin, MD Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Please revise the PRISMA checklist such that the corresponding page number and line numbers of the items on the checklist are presented. 3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. 4.PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: No ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Title: The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysis Outlines: The authors did a systemic review and meta-analysis from 5 academic databases. They calculated the incidence and mortality of pediatric ALL in Indonesia. Comments: This is a well-written article. It provides the updated data of epidemiology of pediatric ALL in Indonesia. I only have one comment for the author. 1. Is it possible to illustrate the trend of incidence and mortality over the study periods? Is the incidence increasing? Is the mortality decreasing? Reviewer #2: This is an important article and represents an excellent review of data sets to understand the incidence of ALL in Indonesia. There are many obstacles/limitations to this project, which are discussed. The paper does need an English writer review and rewrite as there are a number of grammatical changes needed. It is not clear to me what is the time period of all the data reviews. The articles were published from 2007-2021, but not sure how long the time period is and also how this may relate to a changing population size. Has the population size been stable, allowing for an accurate estimate by using the current population size? Some comments to address this would be clarifying. Can you comment on how global improvements in diagnosis and treatment have affected outcome and also how this led to any increased awareness such as reporting may be increasing over the years (suggesting an increasing incidence). The connection between cancer funding in Indonesia and how this data will impact access to this funding is not clear. Would suggest to give a little more info on the local geography as it is implied there are areas of better access, but the common reader may have no understanding of local geography to know how or why this is important. In the methods, please state how the reviewers defined a quality study. Can you suggest more why the incidence rate may be higher before 2010, as it seems more intuitive it would be higher later with improved detection? Give some thoughts as to why the differential mortality rate in different regions. How accurate do you think both the reported incidence and mortality are? In the discussion one are of limitation is heterogeneity, but it is not clear why this specifically refers to. Heterogeneity of the population by region, age, etc? The cancer registry is mentioned in the discussion. Comment more about this, when did it start and do all hospitals throughout the regions report to this? Is this required by the government? Will this cancer registry become a reliable source for calculating incidence and mortality? Finally, how does this work impact a potential improvement in earlier diagnosis, care, and outcomes, as well as documentation for reporting and keeping public records? ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review?** For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0269706.r001
Revision 1
13 May 2022 Author Response Manuscript number: PONE-D-22-09885 Article Title: The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysis PLOS ONE Author's Response: We thank the reviewers for their time and expertise. Please see the specific response to the reviewers enclosed below. Reviewer(s)' Comments to Author: Reviewer #1: Title: The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysis Outlines: The authors did a systemic review and meta-analysis from 5 academic databases. They calculated the incidence and mortality of pediatric ALL in Indonesia. Comments: This is a well-written article. It provides the updated data of epidemiology of pediatric ALL in Indonesia. I only have one comment for the author. 1. Is it possible to illustrate the trend of incidence and mortality over the study periods? Is the incidence increasing? Is the mortality decreasing? Authors' response: Thank you for your valuable input. We did consider charting the trend in incidence and mortality. However, the studies included in this meta-analysis are not suitable for this illustration. This is because while there are multiple studies representing the incidence and mortality in some years, it is not the case for most of the studies. Therefore, we could not extrapolate the incidence from a single period of study in a single institution as the reflection of incidence and mortality in Indonesia and illustrate their trend from that very limited information. Reviewer #2: This is an important article and represents an excellent review of data sets to understand the incidence of ALL in Indonesia. There are many obstacles/limitations to this project, which are discussed. The paper does need an English writer review and rewrite as there are a number of grammatical changes needed. Authors' response: Thank you for your valuable input. We have sent our paper for a professional proofreading check after this comment. We hope it is satisfactory. It is not clear to me what is the time period of all the data reviews. The articles were published from 2007-2021, but not sure how long the time period is and also how this may relate to a changing population size. Has the population size been stable, allowing for an accurate estimate by using the current population size? Some comments to address this would be clarifying. Authors' response: Thank you for your valuable input. We have added the study period on line 172 "The study period for this meta-analysis is between 1997-2019". As for the population size, we have delineated that we used the mid-point year of the study's implementation (lines 132-133). However, we have added an extra sentence on lines 138-140, stating, "The denominator for the population size is tailored to that particular study period. Therefore, this method ensures that our meta-analysis is not significantly affected by the changing number of the population" to clarify the sentence further. This means that although the study period is 1997-2019, the population size will remain stable as it is adjusted to that period. Can you comment on how global improvements in diagnosis and treatment have affected outcome and also how this led to any increased awareness such as reporting may be increasing over the years (suggesting an increasing incidence). Authors' response: Thank you for your valuable input. We have added a discussion on this topic on lines 248-251 "Lastly, rapid advancements have been made in ALL diagnostics, such as genetic and molecular studies. Children who belong to the high-risk groups could be screened and identified earlier, contributing to a higher incidence over the years(1-3)." The connection between cancer funding in Indonesia and how this data will impact access to this funding is not clear. Authors' response: Thank you for your valuable input. We have added a discussion regarding this issue on lines 325-328 "We sincerely hope that after recognizing the high incidence and mortality of ALL in Indonesia as compared to the rest of the world, more funding in childhood cancer is granted in order to obtain a better epidemiological, diagnostic, and treatment for a better future advancement of childhood ALL." Would suggest to give a little more info on the local geography as it is implied there are areas of better access, but the common reader may have no understanding of local geography to know how or why this is important. Authors' response: Thank you for your valuable input. We have given an illustration about this issue on line 306-313 "For instance, a child in remote areas of Jambi (a city in Indonesia) has to travel up to a minimum of eight hours via land transportation to the neighbouring city of Palembang, just to get an access to a pediatric oncologists. If the hospitals could not deliver the necessary care, the child has to travel from Palembang (Sumatera island) to Jakarta (Java island) via land transportation which could take up to 2-3 days or plane which could take 45 minutes. The distance travelled is then coupled with financial issues for lodging stay, transportation costs, and opportunity cost lost as the parents could not work while accompanying their children(8)." In the methods, please state how the reviewers defined a quality study. Authors' response: Thank you for raising this question. We have defined the quality of a study on line 142-144 "The Newcastle-Ottawa scale (NOS) was implemented to assess the quality of cohort studies. A score of 7-9 on NOS implied the study had a good quality, 4-6 indicated a moderate or fair quality, and a score of 0-3 meant that the study had a poor quality(23)". Can you suggest more why the incidence rate may be higher before 2010, as it seems more intuitive it would be higher later with improved detection? Authors' response: Thank you for raising this question. We have attributed this to small sample sizes which could be read furhter on line 270-272 "One of the examples is a higher incidence rate before 2010 which seems counterintuitive as with further advancement of diagnostic techniques, there should be a better detection rate and hence a higher incidence rate(1-3)." Give some thoughts as to why the differential mortality rate in different regions. How accurate do you think both the reported incidence and mortality are? Authors' response: Thank you for raising this question. We have actually discussed this on line 255-260 but we have added a sentence on line 265-266 to further clarify this issue "Underreporting of ALL cases may also be a very plausible explanation to differing mortality and incidence in Indonesia". As to the accuracy, we have conceded about this issue on the limitation section on line 267-270 "There are several limitations to this study. The first limitation is the inclusion of studies with small sample sizes. This introduces a systematic sampling error, which causes a bias in this finding. We have tried to mitigate this issue with a sensitivity analysis of <50(57), but ultimately some bias will still exist". In the discussion one are of limitation is heterogeneity, but it is not clear why this specifically refers to. Heterogeneity of the population by region, age, etc? Authors' response: Thank you for raising this question. In order to be able to determine where does the heterogeneity comes from, a meta-regression needs to be done which could not be done in our study. The cancer registry is mentioned in the discussion. Comment more about this, when did it start and do all hospitals throughout the regions report to this? Is this required by the government? Will this cancer registry become a reliable source for calculating incidence and mortality? Authors' response: Thank you for raising this question. We have added the start of the institution-based cancer registry on line 57 "which develops the first institution-based cancer registry in 2000". Whether all hospitals report to this or required by the government is answered on line 70-74 "Currently, Indonesia is utilizing a national cancer registry called "Sistem Registrasi Kanker di Indonesia (SriKanDi)" but this is not fully adopted and utilized by all hospitals. The government do not make cancer reporting into this registry mandatory, which may explain why it is not fully embraced. Some institutions even choose to develop their own cancer registry, making the national cancer registry unreliable at best(13,14)". As for cancer registry being a reliable source of calculating incidence and mortality is answered on line 329-330 "The urgency for a better cancer registry and policy for a reliable source of estimating incidence and mortality of childhood ALL in Indonesia could not be overstated". Finally, how does this work impact a potential improvement in earlier diagnosis, care, and outcomes, as well as documentation for reporting and keeping public records? Authors' response: Thank you for raising this question. We have adddressed this issue on line 321-330 "Despite the limitations, this study is a step forward in encouraging the government, institutions, researchers, and stakeholders to work together nationally and internationally to create a better cancer registry and hence a more accurate epidemiology of childhood ALL in Indonesia(18, 56, 64). This is the first systematic review and meta-analysis, to our knowledge, that synthesizes the incidence, mortality, and CFR of childhood ALL in Indonesia. We sincerely hope that after recognizing the high incidence and mortality of ALL in Indonesia as compared to the rest of the world, more funding in childhood cancer is granted in order to obtain a better epidemiological, diagnostic, and treatment for a better future advancement of childhood ALL. The urgency for a better cancer registry and policy for a reliable source of estimating incidence and mortality of childhood ALL in Indonesia could not be overstated." We hope that all the reviewers and editor find this response satisfactory. We are more than eager to further revise any comments that are deemed inadequate or necessary for further improvements. Thank you. Attachments Attachment Submitted filename: Authors Response to Reviews.docx https://doi.org/10.1371/journal.pone.0269706.r002
26 May 2022 Decision Letter - Mohamed A Yassin, Editor The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysis PONE-D-22-09885R1 Dear Dr. Dina, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Mohamed A Yassin, MD Academic Editor PLOS ONE Additional Editor Comments (optional): The manuscript can be accepted for publication in its current form Reviewers' comments: https://doi.org/10.1371/journal.pone.0269706.r003
Formally Accepted
30 May 2022 Acceptance Letter - Mohamed A Yassin, Editor PONE-D-22-09885R1 The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysis Dear Dr. Garniasih: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Mohamed A Yassin Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0269706.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .