The OHI index predicts early mortality from organ dysfunction and survival benefit from etoposide in patients with lymphoma

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome that complicates hematologic malignancies. The Optimized HLH Inflammatory (OHI) index, based solely on the combined elevation of soluble CD25 (sCD25; >3900 U/mL) and ferritin (1000 ng/mL) levels, predicts mortality more effectively than the conventional HLH criteria. This study aimed to determine whether mortality in OHI-positive (OHI+) patients is primarily caused by lymphoma or inflammation-related causes. In a multicenter, retrospective study of patients with newly diagnosed lymphoma with sCD25 and ferritin measurements available, patients were classified as OHI+ or OHI negative (OHI-). The 1-year and 3-year overall survival (OS), event-free survival, and causes of death were analyzed, along with predicted vs observed mortality based on other lymphoma-relevant prognostic indexes. Among 135 patients with lymphoma (70 OHI- and 65 OHI+), OHI+ patients had significantly lower OS at 1 year (33% vs 81%; P < .0001) with a median survival of 190 days. OHI+ patients had a 13-fold increased mortality risk (odds ratio, 13.3; 95% confidence interval, 6.0-28.5) despite similar predicted OS based on conventional indexes (72% vs 65%; P = .46). Mortality causes differed significantly. A total of 58% of OHI+ patients died from multiorgan failure, whereas only 6% died from progressive lymphoma. In contrast, 43% of the OHI- patients died from lymphoma progression. The incorporation of etoposide into lymphoma-directed treatment was associated with improved OS in OHI+ T-cell lymphomas (P = .007). These findings underscore the clinical significance of the OHI index as a prognostic tool in lymphoma, to elucidate the mechanisms of mortality, and to identify a high-risk subgroup for which tailored treatments may lead to improved outcomes.

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Publication Details

Journal
Blood Advances
Published
2025-04-18
DOI
https://doi.org/10.1182/bloodadvances.2024014005
Citations
5
Primary Topic
Autoimmune and Inflammatory Disorders Research
Type
article
Field-Weighted Citation Impact
8.85

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article

The OHI index predicts early mortality from organ dysfunction and survival benefit from etoposide in patients with lymphoma

Sarah Nikiforow, Jun Murakami, Abd El Haleem Natour, Martin H. Ellis et al.
5 citations
Blood Advances
Autoimmune and Inflammatory Disorders Research
8.85
article

The OHI index predicts early mortality from organ dysfunction and survival benefit from etoposide in patients with lymphoma

Sarah Nikiforow, Jun Murakami, Abd El Haleem Natour, Martin H. Ellis, Shai Izraeli, Swaminathan P. Iyer, Adi Zoref‐Lorenz, Naval Guastad Daver, Ronit Gurion, Gilad Itchaki, Inbar Cohen, Michael B. Jordan, Gaurav Goyal, Arnon Nagler, Shehab Mohamed, Uri Abadi, Nancy Berliner, Hae Lin Cho, Joanne Yacobovich, Shiri Weinstein, Pia Raanani
article en
5 citations

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome that complicates hematologic malignancies. The Optimized HLH Inflammatory (OHI) index, based solely on the combined elevation of soluble CD25 (sCD25; >3900 U/mL) and ferritin (1000 ng/mL) levels, predicts mortality more effectively than the conventional HLH criteria. This study aimed to determine whether mortality in OHI-positive (OHI+) patients is primarily caused by lymphoma or inflammation-related causes. In a multicenter, retrospective study of patients with newly diagnosed lymphoma with sCD25 and ferritin measurements available, patients were classified as OHI+ or OHI negative (OHI-). The 1-year and 3-year overall survival (OS), event-free survival, and causes of death were analyzed, along with predicted vs observed mortality based on other lymphoma-relevant prognostic indexes. Among 135 patients with lymphoma (70 OHI- and 65 OHI+), OHI+ patients had significantly lower OS at 1 year (33% vs 81%; P < .0001) with a median survival of 190 days. OHI+ patients had a 13-fold increased mortality risk (odds ratio, 13.3; 95% confidence interval, 6.0-28.5) despite similar predicted OS based on conventional indexes (72% vs 65%; P = .46). Mortality causes differed significantly. A total of 58% of OHI+ patients died from multiorgan failure, whereas only 6% died from progressive lymphoma. In contrast, 43% of the OHI- patients died from lymphoma progression. The incorporation of etoposide into lymphoma-directed treatment was associated with improved OS in OHI+ T-cell lymphomas (P = .007). These findings underscore the clinical significance of the OHI index as a prognostic tool in lymphoma, to elucidate the mechanisms of mortality, and to identify a high-risk subgroup for which tailored treatments may lead to improved outcomes.

Blood AdvancesVol. 9(17)
Brigham and Women's Hospital (US), Cincinnati Children's Hospital Medical Center (US), The University of Texas MD Anderson Cancer Center (US), Tel Aviv University (IL), Ono Academic College (IL), Tel Aviv Sourasky Medical Center (IL), Sheba Medical Center (IL), Rabin Medical Center (IL), King Faisal Specialist Hospital & Research Centre (SA), Meir Medical Center (IL), University of Alabama at Birmingham (US), Schneider Children's Medical Center (IL), Dana-Farber Cancer Institute (US), Toyama University Hospital (JP), University of Toyama (JP)
Israel Cancer Research Fund, American Society of Clinical Oncology, Tel Aviv University, National Institutes of Health, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 2%
Autoimmune and Inflammatory Disorders Research
8.85
DOIOpen Access PDFOpenAlex
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