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4414 Serum Soluble Interleukin-2 Receptor Levels in Hairy Cell Leukemia As a Marker of Tumor Burden with Prognostic Value and As a Tool for Disease Monitoring

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, adult, Translational Research, Lymphomas, assays, Clinical Research, Diseases, indolent lymphoma, real-world evidence, Lymphoid Malignancies, Technology and Procedures, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Francesco Angotzi1*, Simone Zoletto, MD1*, Alessandro Cellini, MD1*, Chiara Cavaretta, MD1*, Valeria Ruocco, MD1*, Ivan Zatta, MD1*, Laura Forlani, MD1*, Andrea Serafin, MD1*, Roberta Bertorelle2*, Federica Frezzato, PhD1*, Marco Pizzi, MD3*, Andrea Padoan4*, Daniela Basso4*, Giovanni Pizzolo, MD5*, Livio Trentin1 and Andrea Visentin, MD, PhD1*

1Hematology Unit, Department of Medicine, University of Padova, Padova, Italy
2Immunology and Molecular Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova, ITA
3Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padova, Padua, Italy
4Department of Integrated Diagnostic Medicine, Laboratory Medicine Unit, University of Padova, Padova, Italy
5Department of Engineering for Innovation Medicine, Section of Hematology, University of Verona, Verona, Italy


Neoplastic cells in hairy cell leukemia (HCL) express the α chain of the interleukin-2 receptor on their surface, which is secreted in large amounts in the serum in a soluble form (sIL-2R). High serum levels of sIL-2R have previously been reported in HCL. Thus, we assessed whether serum sIL-2R levels correlated with tumor burden, represented a prognostic factor, and if they could be used as a tool for disease monitoring.


Serum levels of sIL-2R were measured in 59 patients affected by classical HCL followed at the Hematology Unit of Padova University Hospital. To assess whether sIL-2R levels were representative of tumor burden, we evaluated the relationship of pre-therapy sIL-2R levels with other hematologic features such as leukocyte count, the presence of splenomegaly, β-2 microglobulin levels, lactate dehydrogenase (LDH) levels, CD38 expression, the percentages of circulating hairy cells and bone marrow infiltration. In 50 patients we investigated whether post-therapy sIL-2R levels correlated with clinical response and measurable residual disease (MRD) status evaluated by immunohistochemistry according to consensus guidelines.

To determine the usefulness of serum sIL-2R levels for disease monitoring, yearly serial sIL-2R levels were measured in 59 patients, including 5 (8.4%) cases in watch & wait phase and 54 (91.6%) with disease remission after therapy with purine analogues. sIL-2R kinetics were correlated with time to cytopenia (TTC) (hemoglobin <100g/L, neutrophils < 1000/µL or platelets <100.000/µL) and time to next treatment (TTNT).

Serum sIL-2R levels were measured by enzyme-linked immunosorbent assay. The correlation of sIL-2R levels with other variables was evaluated by linear or logistic regression as appropriate. Medians were compared using the Mann-Whitney U test. Survival and univariate analyses for TTC and TTFT were conducted according to the Kaplan-Meier method and Cox proportional hazards model.


The mean age of patients was 60.6 years; 10 were females (17%), and 49 were males (83%). Among treated patients, 47/54 (87%) received cladribine and 7/54 (13%) pentostatin.
Pre-therapy sIL-2R levels significantly correlated with leukocyte count (r2 = 0.13; p = 0.009), β-2 microglobulin levels (r2 = 0.44; p < 0.001), CD38 expression (p = 0.018), the percentage of circulating hairy cells (r2 = 0.17; p = 0.017) and the percentage of bone marrow infiltration (r2 = 0.15; p = 0.009), but not splenomegaly (p = 0.167) or LDH levels (r2 = 0.02; p = 0.369).

We found a significant difference between serum sIL-2R levels measured before and after therapy (median 16.185 vs 599 kU/L respectively; p < 0.001), with a median reduction in sIL-2R levels of 15.628 kU/L after treatment with purine analogues. A similar decrease in sIL-2R levels after therapy was observed in 4 relapsed patients treated with rituximab-vemurafenib (median pre-therapy sIL-2R 11.460 vs. 467 kU/L after treatment, p = 0.03; median reduction 10.848 kU/L).

Among responding patients, the absolute value of log10(sIL-2R) levels measured 6 months after therapy was a predictor of shorter TTNT in univariate analysis (HR 15.14; 95% CI 1.3 – 176; p = 0.03). Furthermore, sIL-2R correlated with the depth of response. Post-therapy median sIL-2R levels were significantly lower in patients achieving a complete remission (CR) versus those who did not (median 568 kU/L for CR vs. 3.272 kU/L for partial remission/stable disease; p = 0.002). A statistically significant difference was also observed in post-therapy sIL-2R levels between MRD- and MRD+ patients (median 502 vs 724 kU/L; p = 0.003) (Figure 1A).

In the patients that underwent yearly serial sIL-2R measurements during follow-up, a rise from the nadir after therapy in serum sIL-2R levels of ≥ 25% between two samples was associated with both shorter TTC (HR 26.2; 95 % CI 3.44 - 200; p < 0.001) (Figure 1B) and TTNT (HR 8.83; 95 % CI 1.9 - 40.9; p < 0.001).


The consistent reduction in sIL-2R levels after therapy and their correlation with other standard disease parameters show how serum sIL-2R levels could be an effective marker of tumor burden in HCL. While more data is required to validate its use in clinical routine, sIL-2R could be used as an effective marker for disease monitoring. Moreover, given the prognostic significance of post-therapy levels, sIL-2R may represent a prognostic factor alongside MRD to identify those patients that are more likely to develop early relapse.

Disclosures: Visentin: Takeda: Speakers Bureau; CSL behring: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

*signifies non-member of ASH