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Pretreatment Hemoglobin Adds Prognostic Information To The NCCN-IPI In Patients With Diffuse Large B-Cell Lymphoma Treated With Anthracycline-Containing Chemotherapy

Authors Clausen MR, Maurer MJ, Ulrichsen SP, Larsen TS, Himmelstrup B, Rønnov-Jessen D, Link BK, Feldman AL, Slager SL, Nowakowski GS, Thompson CA, Pedersen PT, Madsen J, Pedersen RS, Gørløv JS, Cerhan JR, Nørgaard M, D'Amore F

Received 15 June 2019

Accepted for publication 25 September 2019

Published 14 November 2019 Volume 2019:11 Pages 987—996


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Eyal Cohen

Michael R Clausen,1 Matthew J Maurer,2 Sinna Pilgaard Ulrichsen,3 Thomas S Larsen,4 Bodil Himmelstrup,5 Dorthe Rønnov-Jessen,6 Brian K Link,7 Andrew L Feldman,8 Susan L Slager,2 Grzegorz S Nowakowski,9 Carrie A Thompson,9 Per Trøllund Pedersen,10 Jakob Madsen,11 Robert S Pedersen,12 Jette Sønderskov Gørløv,13 James R Cerhan,2 Mette Nørgaard,1 Francesco D’Amore1

1Department of Hematology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Hematology, Odense University Hospital, Odense, Denmark; 5Department of Hematology, Zealand University Hospital, Roskilde, Denmark; 6Department of Hematology, Sygehus Lillebaelt, Vejle, Denmark; 7Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; 8Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; 9Department of Medicine, Mayo Clinic, Rochester, MN, USA; 10Department of Hematology, Sydvestjysk Sygehus, Esbjerg, Denmark; 11Department of Hematology, Aalborg University Hospital, Aalborg, Denmark; 12Department of Hematology, Hospitalsenheden Vest, Holstebro, Denmark; 13Department of Hematology, Rigshospitalet, Copenhagen, Denmark

Correspondence: Michael R Clausen
Department of Hematology, Aarhus University Hospital, Palle Juul-Jensens Blvd 35, Aarhus, Denmark

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.

Keywords: diffuse large B-cell lymphoma, hemoglobin, prognosis, NCCN-IPI

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