https://orcid.org/0000-0003-3218-3633
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Abstract
Background
Hemoglobin (Hgb) concentration at diagnosis is associated with outcome in cancer. In a recently reported simplified 3-factor prognostic score in Hodgkin lymphoma, Hgb, along with age and clinical stage, outperformed the classical International Prognostic Score with seven parameters.
Methods
In the present study, we investigated if pretherapeutic Hgb concentration added prognostic information to the NCCN-IPI in diffuse large B-cell lymphoma. We included patients from the Danish Lymphoma Registry (LYFO; N = 3499) and from the Molecular Epidemiology Resource (MER; N = 1225), Mayo Clinic and University of Iowa. Four sex-specific Hgb groups were defined: below transfusion threshold, from transfusion threshold to below lower limit of normal, from lower limit of normal to the population mean, and above the mean. We used multivariable Cox regression to estimate the hazard rate ratios (HR) and 95% CIs for overall survival (OS) and event-free survival (EFS), adjusting for sex, NCCN-IPI, comorbidity, and rituximab treatment.
Results
Approximately half of the patients had Hgb levels below the lower limit of normal. Compared to patients with Hgb levels above the mean, an inferior OS was directly correlated with lower pretreatment Hgb within the predefined groups (HR=1.23, HR=1.51, and HR=2.05, respectively). These findings were validated in the MER.
Conclusion
Based on multivariable analysis, lower pretreatment Hgb, even within the normal range but below the mean, added prognostic information to established indices such as the NCCN-IPI and the Charlson comorbidity index.
Acknowledgements
The authors gratefully acknowledge help from the departments of clinical biochemistry at the University Hospitals of Aalborg, Odense, Copenhagen-Herlev, Copenhagen-Rigshospitalet, Vejle Hospital, and West Zealand Hospital. The authors also wish to thank the funders of this study: Karen Elise Jensen Foundation, the Program for Clinical Research Infrastructure in Denmark, the Aase & Ejnar Danielsen Foundation, the Eva and Henry Frænkel Memorial Foundation, the Danish Cancer Research Foundation, the Dagmar Marshall Foundation, and Takeda Denmark. The study was also supported by the MER: P50CA97274 grant from National Cancer Institute (NCI), USA, and grant U01CA195568 for The Lymphoma Epidemiology of Outcomes (LEO) Cohort Study. An abstract of this paper was presented at the 15th International Conference on Malignant Lymphoma 18–22 June 2019 as publication only. The abstract was published in Hematological Oncology 2019 vol: 37 pp: 418-420: https://onlinelibrary.wiley.com/doi/10.1002/hon.88_2631.
Author Contributions
All authors contributed toward data analysis, drafting and revising the paper, gave final approved version to be published and agree to be accountable for all aspects of the work.
Disclosure
MRC reports grants from Takeda Denmark, grants from Karen Elise Jensen Foundation, non-financial support from Program for Clinical Research Infrastructure in Denmark, grants from Aase & Ejnar Danielsen Foundation, grants from Eva and Henry Frænkel Memorial Foundation, grants from Danish Cancer Research Foundation, grants from Dagmar Marshall Foundation, during the conduct of the study and non-financial support from Roche, non-financial support from Gilead, outside the submitted work. MM reports being on the advisory board and a consultant of Morphosys, grants from Celgene and grants from Nanostring outside the submitted work. GSN reports grants and personal fees from Celgene, grants and personal fees from Morphosys, personal fees from Selvita, grants from Roche and grants from Nanostring during the conduct of the study. JRC reports grants from NIH during the conduct of the study, grants from NanoString and grants from Celgene outside the submitted work. The authors report no other conflicts of interest in this work.