Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma

Tuba Güllü Koca; Nizameddin Koca; Fazıl Cagrı Hunutlu; Sinem Çubukçu; Azi Ali Ekizoğlu; Bedrettin Orhan; Ömer Candar; Tuba Ersal; Vildan Gürsoy; İbrahim Ethem Pınar; Vildan Ozkocaman; Fahir Özkalemkaş

doi:10.32708/uutfd.2006084

TR EN

Erken Evre Klasik Hodgkin Lenfomada C-Reaktif Protein–Albümin–Lenfosit İndeksi ve Progresyonsuz Sağkalımın Keşifsel Analizi

Abstract

Erken evre klasik Hodgkin lenfomada (kHL) erken nüksü öngörebilen, kolay ulaşılabilir bir biyobelirtecin bulunmaması karşılanmamış bir klinik gereksinimdir; bu çalışmada C-reaktif protein–albümin–lenfosit (CALLY) indeksinin bu hasta grubunda prognostik bilgi taşıyıp taşımadığı araştırılmıştır. Ocak 2010 ile Kasım 2024 arasında doksorubisin, bleomisin, vinblastin ve dakarbazin ile tedavi edilen erken evre kHL tanılı 93 hasta geriye dönük olarak incelenmiştir. CALLY indeksi (albümin × lenfosit sayısı) / C-reaktif protein formülü ile hesaplanmış; prognostik başarımı alıcı işletim karakteristiği, Kaplan–Meier ve Cox regresyon analizleri ile değerlendirilmiştir. İndeksin ek katkısı Harrell uyum indeksi, zamana bağımlı eğri altında kalan alan ve bütünleşik ayrım iyileştirmesi ile incelenmiş; indeks nötrofil/lenfosit, trombosit/lenfosit ve lenfosit/monosit oranları, Prognostik Nutrisyonel İndeks ve Uluslararası Prognostik Skor ile karşılaştırılmıştır. Ortanca izlem süresi 71 ay olup 19 progresyonsuz sağkalım olayı gözlenmiştir. En uygun eşik değer 5,87 bulunmuştur. Beş yıllık progresyonsuz sağkalım, düşük ve yüksek indeks gruplarında sırasıyla %58,7 ve %94,2 (p<0,001), unfavorable alt grupta ise %52,6 ve %82,4 (p=0,023) saptanmıştır. Düşük indeks daha kötü progresyonsuz sağkalım ile bağımsız olarak ilişkili bulunmuş (risk oranı 3,44, %95 güven aralığı 1,09–10,89, p=0,036) ve indeksin favorable/unfavorable sınıflamasına eklenmesi ayrım gücünü artırmıştır (uyum indeksi 0,745'ten 0,807'ye; 60. ayda zamana bağımlı eğri altında kalan alan 0,767'den 0,846'ya, p=0,030). CALLY indeksi incelenen belirteçler arasında en yüksek uyum indeksine sahip olmakla birlikte yalnızca Uluslararası Prognostik Skoru anlamlı biçimde aşmıştır. Genel sağkalımda fark saptanmamıştır. Sonuç olarak tedavi öncesi düşük CALLY indeksi erken evre kHL'de daha kısa progresyonsuz sağkalım ile ilişkilidir; hipotez üretici nitelikteki bu bulgu dış ve pozitron emisyon tomografisi uyarlanmış doğrulama gerektirmektedir.

Keywords

Ethical Statement

Approving Committee: Bursa Uludağ University, Faculty of Medicine, Clinical Research Ethics Committee Approval Date: December 12, 2023 Decision No: 2023-27/13

Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma

Abstract

An easily accessible biomarker to predict early relapse in early-stage classical Hodgkin lymphoma (cHL) remains an unmet clinical need, and this study explored whether the C-reactive protein–albumin–lymphocyte (CALLY) index provides prognostic information in this setting. Ninety-three patients with early-stage cHL treated with doxorubicin, bleomycin, vinblastine, and dacarbazine between January 2010 and November 2024 were analyzed retrospectively. The CALLY index was calculated as (albumin × lymphocyte count) / C-reactive protein, and its prognostic performance was assessed using receiver operating characteristic analysis, Kaplan–Meier analysis, and Cox regression. Incremental value was assessed using Harrell's concordance index, time-dependent area under the curve, and integrated discrimination improvement, and these indices were compared with the neutrophil-to-lymphocyte, platelet-to-lymphocyte, and lymphocyte-to-monocyte ratios, the Prognostic Nutritional Index, and the International Prognostic Score. Median follow-up was 71 months, and 19 progression-free survival events occurred. The optimal cut-off was 5.87. Five-year progression-free survival was 58.7% versus 94.2% for low versus high values (p<0.001) and 52.6% versus 82.4% within the unfavorable subgroup (p=0.023). A low index was independently associated with worse progression-free survival (hazard ratio 3.44, 95% confidence interval 1.09–10.89, p=0.036) and adding it to the favorable/unfavorable classification improved discrimination (concordance index 0.745 to 0.807; time-dependent area under the curve at 60 months 0.767 to 0.846, p=0.030). The CALLY index showed the highest concordance index among the markers examined, although it significantly exceeded only the International Prognostic Score. Overall survival did not differ. A low pre-treatment CALLY index was therefore associated with shorter progression-free survival in early-stage cHL; this hypothesis-generating finding requires external and positron-emission-tomography-adapted validation.

Keywords

Ethical Statement

Approving Committee: Bursa Uludağ University, Faculty of Medicine, Clinical Research Ethics Committee Approval Date: December 12, 2023 Decision No: 2023-27/13

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Details

Primary Language

English

Subjects

Haematology

Journal Section

Research Article

Authors

Tuba Güllü Koca ^*
0000-0003-4168-2821
Türkiye

Nizameddin Koca
0000-0003-1457-4366
Türkiye

Fazıl Cagrı Hunutlu
0000-0002-4991-9830
Türkiye

Sinem Çubukçu
0000-0001-9623-8096
Türkiye

Azi Ali Ekizoğlu This is me
0009-0001-1509-2732
Türkiye

Bedrettin Orhan
0000-0003-3970-2344
Türkiye

Ömer Candar
0000-0001-7602-6926
Türkiye

Tuba Ersal
0000-0001-5419-3221
Türkiye

Vildan Gürsoy
0000-0002-3645-9345
Türkiye

İbrahim Ethem Pınar
0000-0001-9907-1498
Türkiye

Vildan Ozkocaman
0000-0003-0014-7398
Türkiye

Fahir Özkalemkaş
0000-0001-9710-134X
Türkiye

Publication Date

September 18, 2026

Submission Date

July 29, 2026

Acceptance Date

August 22, 2026

Published in Issue

Year 2026 Volume: 52

DOI

https://doi.org/10.32708/uutfd.2006084

IZ

https://izlik.org/JA74GM93RE

Cite

RIS / Bibtex

APA

Güllü Koca, T., Koca, N., Hunutlu, F. C., Çubukçu, S., Ekizoğlu, A. A., Orhan, B., Candar, Ö., Ersal, T., Gürsoy, V., Pınar, İ. E., Ozkocaman, V., & Özkalemkaş, F. (2026). Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma. Journal of Uludağ University Medical Faculty, 52. https://doi.org/10.32708/uutfd.2006084

AMA

1.Güllü Koca T, Koca N, Hunutlu FC, et al. Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma. Journal of Uludağ University Medical Faculty. 2026;52. doi:10.32708/uutfd.2006084

Chicago

Güllü Koca, Tuba, Nizameddin Koca, Fazıl Cagrı Hunutlu, et al. 2026. “Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma”. Journal of Uludağ University Medical Faculty 52 (September). https://doi.org/10.32708/uutfd.2006084.

EndNote

Güllü Koca T, Koca N, Hunutlu FC, Çubukçu S, Ekizoğlu AA, Orhan B, Candar Ö, Ersal T, Gürsoy V, Pınar İE, Ozkocaman V, Özkalemkaş F (September 1, 2026) Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma. Journal of Uludağ University Medical Faculty 52

IEEE

[1]T. Güllü Koca et al., “Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma”, Journal of Uludağ University Medical Faculty, vol. 52, Sept. 2026, doi: 10.32708/uutfd.2006084.

ISNAD

Güllü Koca, Tuba - Koca, Nizameddin - Hunutlu, Fazıl Cagrı - Çubukçu, Sinem - Ekizoğlu, Azi Ali - Orhan, Bedrettin - Candar, Ömer et al. “Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma”. Journal of Uludağ University Medical Faculty 52 (September 1, 2026). https://doi.org/10.32708/uutfd.2006084.

JAMA

1.Güllü Koca T, Koca N, Hunutlu FC, Çubukçu S, Ekizoğlu AA, Orhan B, Candar Ö, Ersal T, Gürsoy V, Pınar İE, Ozkocaman V, Özkalemkaş F. Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma. Journal of Uludağ University Medical Faculty. 2026;52. doi:10.32708/uutfd.2006084.

MLA

Güllü Koca, Tuba, et al. “Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma”. Journal of Uludağ University Medical Faculty, vol. 52, Sept. 2026, doi:10.32708/uutfd.2006084.

Vancouver

1.Tuba Güllü Koca, Nizameddin Koca, Fazıl Cagrı Hunutlu, Sinem Çubukçu, Azi Ali Ekizoğlu, Bedrettin Orhan, Ömer Candar, Tuba Ersal, Vildan Gürsoy, İbrahim Ethem Pınar, Vildan Ozkocaman, Fahir Özkalemkaş. Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma. Journal of Uludağ University Medical Faculty. 2026 Sep. 1;52. doi:10.32708/uutfd.2006084

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The title of the study should clearly and accurately reflect the study. Titles should not exceed two lines and should be written with the first letter of each word capitalized. Title should not contain abbreviations or acronyms.
Abstract
The abstract should be written as a single text without being divided into sections (unstructured). The English and Turkish abstracts should not exceed 250 words, and the English title and abstract should be equivalent to the Turkish title and abstract. The abstract should briefly state the purpose, scope, and methods of the study, and the main findings should be detailed enough to support the conclusion reached. The first sentence should cover the purpose of the study, and the last sentence should encompass the result of the study. The new and important aspects of the study or observations should be emphasized. Abstracts should not contain non-standard abbreviations.
Keywords
Keywords increase the discoverability of articles. Under the Turkish and English abstract, according to the Index Medicus Medical Subject Headings (MESH) (https://meshb.nlm.nih.gov), there should be no fewer than three and no more than six keywords.
If there are no terms that match the newly entered terms in the Index Medicus medical subject headings, existing terms can be used.

ORIGINAL ARTICLE
In the original article, the main text should include the introduction, materials and methods, findings, discussion and conclusion, acknowledgments (optional), references, table titles and tables, figures and figure legends. Abbreviations should be defined in the Abstract, main text, figures, and tables after their first use. Only widely accepted abbreviations should be used. Drug and chemical names should be specified using generic or standard chemical nomenclature. Measurement units should be in accordance with the International System (SI); however, clinical data may be presented in traditional units when deemed more appropriate.
Introduction: The purpose of the article, the rationale for the study or observation should be summarized, and the data or results of the study should not be explained.
Materials and Methods: It should be stated that the experimental and clinical studies included in the article were approved by the relevant ethics committee. Established methods should be referenced, and new methods should be briefly explained.
Biostatistical Analysis: In the last paragraph of the Materials and Methods section, the statistical analyses used should be specified. The p-values should be explicitly stated. The article is evaluated by the Biostatistics Editor before being sent to scientific advisors, and corrections are requested from the author when necessary.
Findings: The data obtained from the study should be written comprehensively and clearly. The statistical results of the data included in the findings should contain information on the mean, standard error, p-value, and F-value. Tables and figures (drawings, graphs, and photographs) should be numbered in the order they appear in the text as explained below, and references to tables and/or figures should be made in the relevant sections of the findings.
Discussion and Conclusion: The findings obtained from the study should be discussed by comparing them with the literature, the limitations of the study should be stated, and the contribution of the study to the literature should be summarized in the conclusion. Both the discussion and conclusion should be included under this heading, and the conclusion section should be provided in the last paragraph of this heading.

Acknowledgements (Optional): The names of individuals who have made partial contributions to the work, other than the authors, can be written in this section. Additionally, information about the project and source that supported the study can be entered in this section.

References: The sources used should be numbered in the order they appear in the text, provided as superscripts in the text, and formatted according to the AMA (American Medical Association) style. The abbreviations used should conform to Index Medicus and Science Citation Index. Personal communications, unpublished articles in preparation, or other unpublished data should not be cited as sources. In articles with fewer than six authors, all authors' names should be listed. If there are six or more authors, the first three should be listed followed by "et al."
Examples:
Article:
White NP, Kim D, Fos K. Posterior fossa aneurysms. J Neurosurg. 1990;72(1):345-349.
Book:
Norman IJ, Redfern SJ, (eds). Mental health care for elderly people. 3rd edition. New York: Churchill Livingstone; 1996.

Book Chapter:
Jane JA, Persing JA. Neurosurgical treatment of craniosynostosis. In: Cohen MM, Kim D (eds). Craniosynostosis: Diagnosis and management. 2nd edition. NewYork: Raven Press; 1986: 249-295.
Theses:
Kanpolat Y. Trigeminal Gangliona Deneysel Perkütan Giriş ve Radyofrekans Termik Lezyonun Histopatolojik Değerlendirilmesi (Doktara/Uzmanlık Tezi). Ankara Üniversitesi; 1978.
Extensive information on various other reference management software can be found on the "International Committee of Medical Journal Editors" website: www.icmje.org.
Unpublished observations and personal communications cannot be used as sources. Accepted, unpublished articles that have received a DOI can be included in the references with the word "in press" indicated.
In sources obtained from the internet, the full access address and access date must be included.
Tables: Tables should be placed after the "References" section in the main text file. Each table should be written on a separate page, along with its title and footnotes. Each table should contain an appropriate title that explains its content, and the title should be placed above the table. Tables should be numbered consecutively in the order they appear in the main text, and mentions to the tables in the text should always follow the consecutive numbering order. In the numbering of tables, Roman numerals should be used (Table I, Table II, III, IV…). If abbreviations are used in the table, they should be explained as footnotes below the table.
Figures: Within the scope of the journal, photographs, graphs, and/or illustrations are defined as "Figures." All figures must be placed after the "Tables" section in the main text file and should also be prepared according to the specified features and uploaded separately to the system. Each figure should be numbered consecutively in the main text according to the order in which they appear (Figure 1, Figure 2,…). Figure files must be in JPEG or TIFF format. Other formats are not accepted. In figures with multiple sections, each section should be indicated with lowercase letters (a, b, c, etc.). Figures containing multiple sections should be prepared as a single combined figure and uploaded to the manuscript submission system as a single file.
The titles and descriptions of all figures should be provided on a separate page after the "Figures" section in the full text file, and the figure files uploaded to the system should not contain titles and descriptions. If an abbreviation is used in the figure, the abbreviations should be explained as a footnote under the figure. If the figure is a quotation from another source, the source should be cited in the figure caption.
Figures containing photographs should be saved at a minimum resolution of 600x600 pixels and scaled to fit one or two columns in magazine size.
Graphics and illustrations should be prepared with a resolution of at least 300x300 pixels and scaled to fit one or two columns.

CASE REPORT
Cases that contribute to the literature and have publication value should be submitted. Title (in English and Turkish), abstract (in English and Turkish), keywords (in English and Turkish) (at least 3, at most 6), introduction, case report (patient presentation, laboratory or other findings, diagnosis and explanation of the outcome), discussion and conclusion (what is new in this case report, how it differs from previously published cases, and how it is related), references, table titles and tables, figures and figure titles sections should be included.
For all case reports submitted to the journal, informed consent must be obtained from the patient. This consent must be specified in the 'case report' section of the main text.
The number of authors for case reports is limited to six.
REVIEW
The title (in English and Turkish), abstract (in English and Turkish), keywords (in English and Turkish), and main text sections should be included.
The number of authors for compilations is limited to three.
LETTER TO THE EDITOR
The title (in English and Turkish), abstract (in English and Turkish), keywords (in English and Turkish), and main text sections should be included.
Article Submission Checklist:
Before submitting the articles, compliance with writing rules should be checked, and any deficiencies should be addressed using the checklist below.
1. It should be ensured that the journal's writing rules, copyright, and author responsibilities are seen, read, and understood.
2. It should be ensured that the article has not been published or submitted to another journal and is not under review elsewhere.
3. It should be ensured that the study complies with research ethics rules.
4. It should be ensured that all authors' names are written.
5. Mandatory forms (Cover Letter, Title Page, Copyright Form, and Author Contribution Form) should be downloaded from the system, filled out, and then re-uploaded to the system.
6. Main Text:
It should consist of the following sections:
- Article Title (English and Turkish)
-Summary (in English and Turkish)
-Keywords (English and Turkish)
-Introduction
-Materials and Methods
-Results
-Discussion and Conclusion
-References (Must comply with the journal's guidelines.)
-Acknowledgement
-Tables
-Figures and figure captions with subtitles

ETHICAL PRINCIPLES
The Journal of Uludağ University Medical Faculty adopts and adheres to the ethical principles, frameworks, and standards established by the Committee on Publication Ethics (COPE).
The Journal of Uludağ University Medical Faculty requires the documentation of the Ethics Committee Decision in clinical studies involving humans, experimental studies using laboratory animals, and survey studies. These documents must also include a page with the signatures of the Committee Members (a cover letter alone is insufficient). In the article text, the Ethics Committee information (Committee name, decision date, decision number) should be included in the "Materials and Methods" section.
In case reports, an ethics committee decision is not required, but consent must be obtained from the cases included in the article, and this must be stated within the article.
Ethics committee approval is not required for reviews, but it is expected that the corresponding author uploads a signed statement indicating this to the system.
Article authors must adhere to universal publication ethics rules.

Ethical Responsibilities of Authors
Authors must state that their articles are their original work and that all data in the article are real and original. Authors are responsible for ensuring that the data presented in their articles is accurate and representative of the article. To ensure transparency, authors may be asked to submit their raw data or additional data along with the article. Authors are responsible for providing supplementary and auxiliary materials. The articles submitted to the journal must not have been published elsewhere or be under consideration for publication. However, authors can submit their articles to the Journal after receiving a rejection letter from another publisher. Theses and graduation theses that are not archived online are considered original and unpublished. However, authors who submit articles using the content and data of their theses should mention this in the Acknowledgments section.

Authors must comply with the authorship criteria listed in the "Authorship" section. The level of their contributions should be defined in the 'Authorship Contribution Form' section. Authors are responsible for retracting and correcting errors. Authors must disclose and declare any conflicts of interest to the Editors. If there is no conflict of interest, the authors should also declare this in their article. Authors should specify all sources used in the creation of the articles. Authors should cite relevant and verified literature to support their scientific work and should not use unrelated sources that could assist other research/journals.

The corresponding author is the main owner of the article, so they can withdraw their articles before entering the review process or when a revision is requested. Authors cannot make significant changes to the article or withdraw it without a serious reason after the paper has been accepted.

Authors are obliged to inform the journal editor or publisher of any errors or mistakes in a published, preprint, or review-stage article and to cooperate with the chief editor to correct or retract the article. Authors should avoid submitting a manuscript based on the same dataset, study, or experiment for publication. The journal reserves the right to withhold publication or reject articles identified as plagiarism, ethical violations, undisclosed prior publication, or conflicts of interest, even after an editorial acceptance decision.

All articles are examined for similarity or plagiarism. Articles submitted to the journal for evaluation are examined using the "Plagiarism Detection Program" (iThenticate), and articles with a similarity rate above 20% are returned to the authors.

Authors should maintain open and constructive communication with other editors and reviewers. (Inappropriate language or destructive behavior is unacceptable. The journal follows COPE guidelines when dealing with such situations.

Ethical Responsibilities of Referees
Reviewers must keep all information related to the articles confidential and treat it as privileged information. Evaluations should be conducted objectively without personal criticism of the author. The authors' self-identification should not influence their comments and decisions. Reviewers may identify relevant published work that has not been cited by the authors. Reviewers should not review articles that have conflicts of interest arising from competitive, collaborative, or other relationships or connections with the authors, companies, or institutions connected to the articles.
Reviewers are obliged to complete the assigned tasks on time and to inform the journal in case of the need for an extension or withdrawal from the task.

The Ethical Responsibilities of Editors
Journal Editors (Chief Editor, Editor, or Editorial Board Members) have full responsibility and authority to reject/accept an article. Editors always consider the needs of authors and readers while striving to improve the publication. Editors take the necessary precautions to keep articles and editorial reports confidential. Articles, editorial reports, and obtained information are not shared or disclosed for any reason.
Editorial decisions in the journal are based solely on the significance, originality, clarity, and suitability of the articles for publication. Editors ensure that all research materials published in the Journal comply with internationally accepted ethical standards. Editors are obliged to take action and make all reasonable efforts to resolve the issue when they encounter any abuse, unethical behavior, or misconduct related to research and publication ethics, whether the article is published or unpublished.
In articles submitted by editors or members of the editorial board of the journal, the process is conducted in such a way that the editor or board member who is the author of the article does not participate in the evaluation and decision stages.
Editors, editorial staff, authors, reviewers, and committee members conduct the evaluation process in a manner that does not allow any conflicts of interest.
Editors are responsible for completing assigned tasks on time, facilitating the review process, remaining impartial, and ensuring that the review process progresses consistently and fairly.

PUBLISHING POLICY
The Journal of Uludağ University Medical Faculty is an open-access journal that publishes for scientific purposes and does not request any fees at any stage of the process. Articles submitted for evaluation to the journal are primarily subjected to a format review, and a similarity check is conducted at this stage. Subsequently, a priority assessment for publication in the journal is conducted by the chief editor, editor, and/or the relevant section editor. Due to the large number of articles submitted to our journal, in this evaluation, articles determined not to have priority are not considered for review and are returned to the author. A Section Editor from the Editorial Board is assigned to the articles that are accepted for review. The section editor obtains opinions from at least 2 scientific advisors and informs the editor of the decision. In the case of equal opinions from scientific advisors (1 rejection, 1 acceptance/revision), the article may be sent to a third reviewer by the section editor, or the section editor may provide her/his opinion based on her/his own evaluation. The final decision is made by the Chief Editor and/or the Editor and communicated to the author.
The review period in our journal is an average of 60 days. However, for various reasons, this period can vary between 15 days and 120 days.

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Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma

Erken Evre Klasik Hodgkin Lenfomada C-Reaktif Protein–Albümin–Lenfosit İndeksi ve Progresyonsuz Sağkalımın Keşifsel Analizi

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Exploratory Analysis of the C-Reactive Protein–Albumin–Lymphocyte Index and Progression-Free Survival in Early-Stage Classical Hodgkin Lymphoma

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