Table 1.
Patient demographics and diagnosis.
| Patient ID | Age (years) | Sex | Lymphoma Subtype |
|---|---|---|---|
| P1 | 48 | M | ALK-negative anaplastic large cell lymphoma |
| P2 | 40 | M | Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) |
| P3 | 64 | M | ALK-negative anaplastic large cell lymphoma |
| P4 | 57 | M | Nodal T-follicular helper cell lymphoma (nTFHL) |
| P5 | 53 | M | Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) |
| P6 | 69 | M | ALK-negative anaplastic large cell lymphoma |
| P7 | 49 | M | Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) |
| P8 | 40 | F | Adult T-cell leukemia/lymphoma (ATLL), lymphoma type |
| P9 | 56 | F | Enteropathy-associated T-cell lymphoma |
| P10 | 66 | M | ALK-negative anaplastic large cell lymphoma |
| P11 | 45 | M | Adult T-cell leukemia/lymphoma (ATLL), chronic type |
| P12 | 45 | F | Adult T-cell leukemia/lymphoma (ATLL), unfavorable chronic type |
| P13 | 48 | F | Extranodal NK/T-cell lymphoma, nasal type (ENKTL) |
| P14 | 40 | M | Adult T-cell leukemia/lymphoma (ATLL), lymphoma type |
| P15 | 60 | F | Cutaneous T-cell lymphoma (CTCL) |
| P16 | 60 | F | ALK-negative anaplastic large cell lymphoma |
| P17 | 60 | M | Mycosis fungoides with large-cell transformation (LCT-MF) |
| P18 | 55 | M | Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI) |
| P19 | 40 | M | Adult T-cell leukemia/lymphoma (ATLL), acute type |
| P20 | 78 | M | Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI) |
Table 2.
Clinical characteristics, plasma IL-35 levels, first-line treatment, response, transplantation, and outcomes.
| Patient | Diagnosis | IPI | IL-35 (pg/mL) | First-line treatment | Best response | HSCT | OS / status (months) | Cause of death |
|---|---|---|---|---|---|---|---|---|
| P1 | ALK-negative ALCL | Low | 32.97 | CHOEP | PD | No | 7 / Deceased | Disease progression / HLH |
| P2 | PTCL-NOS | Low | 32.00 | CHOEP + HD-MTX | CR | Auto-HSCT | 63 / Alive | — |
| P3 | ALK-negative ALCL | High | 3.94 | CHOP | PD | No | 3 / Deceased | Disease progression |
| P4 | Nodal TFH lymphoma | High-intermediate | 10.39 | CHOEP | PR | No | 7 / Deceased | Disease progression |
| P5 | MEITL | Low | 6.84 | CHOEP | CR | No | 14 / Deceased | Disease progression (CNS) |
| P6 | ALK-negative ALCL | High | 153.94 | BV-CHP | CR | No | 42 / Alive | — |
| P7 | PTCL-NOS | Low-intermediate | 2.97 | CHOEP | PD | No | 2 / Deceased | Disease progression |
| P8 | ATLL, lymphoma type | Low | 2.65 | CHOEP | PR | Allo-HSCT | 12 / Deceased | Disease progression |
| P9 | EATL | Low (IPI 0) | 26.52 | Newcastle regimen | CR | No | 19 / Alive | — |
| P10 | ALK-negative ALCL | High-intermediate (IPI 3) | 39.74 | BV-CHP | SD | No | 16 / Alive | — |
| P11 | ATLL, chronic type | Low (IPI 0) | 32.32 | PEG-IFN + zidovudine | PR | No | 26 / Alive | — |
| P12 | ATLL, unfavorable chronic type | Low (IPI 0) | BDL | PEG-IFN + zidovudine | PR | No | 16 / Alive | — |
| P13 | Extranodal NK/T-cell lymphoma, nasal type | High-intermediate (IPI 3) | 1.16 | SMILE | PD | No | 4 / Deceased | Disease progression (CNS) |
| P14 | ATLL, lymphoma type | Low-intermediate | 13.26 | CHOEP | PD | No | 4 / Deceased | Disease progression |
| P15 | CTCL | Low | 1.29 | Excision | CR | No | 79 / Alive | — |
| P16 | ALK-negative ALCL | Low-intermediate | 32.37 | BV-CHP | CR | Auto-HSCT | 15 / Alive | — |
| P17 | MF with large-cell transformation | Low | 12.67 | Gemcitabine | CR | No | 45 / Alive | — |
| P18 | Nodal TFH lymphoma, angioimmunoblastic type | Low | 2.62 | GDP | PR | Allo-HSCT | 30 / Deceased | Sepsis |
| P19 | ATLL, acute type | High-intermediate | 3.39 | CHOEP | PD | No | 4 / Deceased | Disease progression (CNS) |
| P20 | Nodal TFH lymphoma, angioimmunoblastic type | High-intermediate (IPI 3) | 138.75 | CHOP | CR | No | 44 / Alive | — |
[i] Abbreviations: ALCL, anaplastic large cell lymphoma; Allo-HSCT, allogeneic hematopoietic stem-cell transplantation; ATLL, adult T-cell leukemia/lymphoma; Auto-HSCT, autologous hematopoietic stem-cell transplantation; BDL, below detection limit; BV-CHP, brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone; CNS, central nervous system; CR, complete response; CTCL, cutaneous T-cell lymphoma; EATL, enteropathy-associated T-cell lymphoma; HLH, hemophagocytic lymphohistiocytosis; MEITL, monomorphic epitheliotropic intestinal T-cell lymphoma; MF, mycosis fungoides; PD, progressive disease; PR, partial response; PTCL-NOS, peripheral T-cell lymphoma, not otherwise specified; SD, stable disease; TFH, T-follicular helper. For patients alive at the October 1, 2026 data-lock date, OS represents censored follow-up duration to the last documented clinical contact on or before that date. Cause of death is shown only for deceased patients.
Figure 1.
Plasma IL-35 concentrations at diagnosis in mature T-cell neoplasms.
Individual numerical estimates are shown on a logarithmic scale. The dashed horizontal line indicates the manufacturer's analytical sensitivity (9.38 pg/mL), and the dotted horizontal line indicates the lower limit of the validated range (15.63 pg/mL). Numerical estimates below these thresholds are displayed to illustrate the observed distribution but should not be interpreted as equally precise quantitative measurements. The sample reported as below the detection limit is not shown.
Figure 2.
Kaplan–Meier analysis of overall survival according to plasma IL-35 relative to the manufacturer's analytical sensitivity threshold. Patients were categorized as IL-35 ≥9.38 pg/mL (n = 11) or <9.38 pg/mL (n = 9). Higher IL-35 was associated with longer overall survival (log-rank p = 0.029; Cox HR 0.26, 95% CI 0.07–0.99; p = 0.049). Censored observations are indicated by tick marks. Numbers at risk are shown below the plot.
Table 3.
Descriptive distribution of disease entity, IPI category, and first-line treatment according to the primary IL-35 assay threshold.
| Characteristic | IL-35 <9.38 pg/mL (n=9) | IL-35 ≥9.38 pg/mL (n=11) |
|---|---|---|
| ALK-negative ALCL | 1 (11.1%) | 4 (36.4%) |
| PTCL-NOS | 1 (11.1%) | 1 (9.1%) |
| Nodal TFH lymphoma | 1 (11.1%) | 2 (18.2%) |
| ATLL | 3 (33.3%) | 2 (18.2%) |
| Intestinal T-cell lymphoma (EATL/MEITL) | 1 (11.1%) | 1 (9.1%) |
| ENKTL | 1 (11.1%) | 0 |
| Primary cutaneous T-cell neoplasm | 1 (11.1%) | 1 (9.1%) |
| IPI category Low | 5 (55.6%) | 5 (45.5%) |
| IPI category Low-intermediate | 1 (11.1%) | 2 (18.2%) |
| IPI category High-intermediate | 2 (22.2%) | 3 (27.3%) |
| IPI category High | 1 (11.1%) | 1 (9.1%) |
| First line treatment CHOEP | 4 (44.4%) | 3 (27.3%) |
| First line treatment BV-CHP | 0 | 3 (27.3%) |
| First line treatment CHOP | 1 (11.1%) | 1 (9.1%) |
| First line treatment CHOEP + HD-MTX | 0 | 1 (9.1%) |
| First line treatment PEG-IFN + zidovudine | 1 (11.1%) | 1 (9.1%) |
| Newcastle regimen | 0 | 1 (9.1%) |
| SMILE | 1 (11.1%) | 0 |
| Excision | 1 (11.1%) | 0 |
| Gemcitabine | 0 | 1 (9.1%) |
| GDP | 1 (11.1%) | 0 |
[i] Data are presented as n (% within IL-35 group). No inferential comparisons were performed. ATLL subtypes were grouped together; EATL and MEITL were grouped as intestinal T-cell lymphomas; the two primary cutaneous neoplasms were grouped together. BDL values were assigned to the <9.38 pg/mL group according to the assay-defined primary threshold.