The Impact of Tumor Hypoxia Modulation on sIL-2R Levels in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) Patients Undergoing Chemotherapy: A Randomized Clinical Trial

Rizky, Daniel; Tandarto, Kevin; Pangarsa, Eko Adhi; Naibaho, Ridho M.; Kurniawan, Sigit P.; Santosa, Damai; Setiawan, Budi; Suharti, Catharina

doi:10.31557/APJCP.2024.25.4.1315

The Impact of Tumor Hypoxia Modulation on sIL-2R Levels in Newly Diagnosed Diffuse Large B Cell Lymphoma (DLBCL) Patients Undergoing Chemotherapy: A Randomized Clinical Trial

Document Type : Research Articles

Authors

¹ Division of Hematology and Medical Oncology, Department of Internal Medicine, Faculty of Medicine Diponegoro University, Dr. Kariadi General Hospital, Semarang, Indonesia.

² Department of Hematology/Medical Oncology, A. M. Parikesit Hospital and A. W. Sjahranie Hospital, Mulawarman School of Medicine, Samarinda, East Kalimantan, Indonesia.

³ Department of Hematology/ Medical Oncology, Department of Internal Medicine, Lambung Mangkurat University/Ulin General Hospital, Banjarmasin, and Hadji Boejasin General Hospital, Tanah Laut, Indonesia.

10.31557/APJCP.2024.25.4.1315

Abstract

Objective: Tumor hypoxia induces the production of Hypoxia-Inducible Factor (HIF)-1 alpha, which interacts with NF-kB, leading to cancer proliferation and metastasis. This study investigated the effect of tumor hypoxia modulation using carbogen (95% O2 and 5% CO2) and nicotinamide on reducing soluble interleukin-2 receptor (sIL-2R) levels in newly diagnosed DLBCL patients with tissue overexpression of HIF-1α ≥10%. Material and Methods: A prospective randomized controlled clinical trial was conducted at Dr. Kariadi Hospital in Semarang, Indonesia, from 2021 to 2022. Newly diagnosed DLBCL patients with tissue HIF-1α ≥10% were randomized into an intervention group (nicotinamide 2,000 mg + carbogen 10 liters/min during R-CHOP) and a control group (R-CHOP alone) for one cycle. sIL-2R levels were measured in the blood before and after intervention. Results: The intervention group showed a significant reduction in sIL-2R levels after chemotherapy (p=0.026), with 85% of samples exhibiting a decrease. In contrast, only 45% of samples in the control group demonstrated a decrease in sIL-2R levels (p=0.184). The median sIL-2R level decreased from 139.50 pg/mL to 70.50 pg/mL in the intervention group, while the control group exhibited an increase from 182.50 pg/mL to 250.00 pg/mL following one cycle of chemotherapy. Conclusion: Tumor hypoxia modulation led to a significant decrease in serum sIL-2R levels, potentially through improvements in the crosstalk between hypoxia and inflammation pathways.

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