Simple Blood Test Ratio Predicts Survival in Hodgkin Lymphoma Patients on Immunotherapy

A routine blood test that costs pennies to perform may help doctors predict which patients with relapsed or refractory classic Hodgkin lymphoma will benefit from PD-1-based salvage therapy, according to a new retrospective study published in BMC Cancer. The research, led by Gengcong Luo and Weilin Xia of Jieyang People’s Hospital together with collaborators at Sun Yat-Sen University Cancer Center and other Chinese institutions, found that an elevated platelet-to-lymphocyte ratio, a simple calculation derived from a standard complete blood count, was strongly associated with poorer progression-free survival and overall survival in this hard-to-treat patient population. The finding, if confirmed prospectively, could give oncologists an inexpensive and widely accessible tool for risk stratification at a moment when treatment decisions carry enormous consequences.

Classic Hodgkin lymphoma is one of the great success stories of modern hematology, with the majority of newly diagnosed patients cured by combination chemotherapy, often supplemented with radiation or targeted agents. Yet a stubborn minority of patients either fail to achieve a complete remission or see their disease return after an initial response. For these individuals, the therapeutic landscape changed dramatically with the arrival of immune checkpoint inhibitors targeting programmed cell death protein 1, or PD-1, a receptor that tumors exploit to suppress the immune response against them. Drugs in this class, including nivolumab and pembrolizumab, have produced durable responses in a substantial fraction of relapsed or refractory patients and are now frequently woven into salvage regimens, either alone or in combination with chemotherapy, before patients proceed to autologous stem cell transplantation.

The problem, as the study’s authors note, is that validated biomarkers for this specific setting remain scarce. Clinicians can draw on established prognostic indices for newly diagnosed Hodgkin lymphoma, but those tools were not designed to predict outcomes under PD-1 inhibition. In the absence of reliable predictors, treatment intensification decisions, such as whether to proceed rapidly to transplantation or to extend immunotherapy exposure, rest largely on clinical judgment. Inflammation-based ratios computed from routine blood counts have attracted growing interest across oncology precisely because they capture, in a single number, the balance between a tumor-promoting inflammatory state and the host’s antitumor immune capacity. The neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio are the two most studied of these indices, and both have shown prognostic value in a range of solid tumors and hematologic malignancies.

To test whether these ratios matter in relapsed or refractory classic Hodgkin lymphoma treated with PD-1-based salvage therapy, the researchers assembled a retrospective cohort of 127 patients who received such treatment at two hospitals between 2018 and 2023. The cohort comprised 48 patients, or 37.8 percent, whose disease had relapsed after remission, and 79 patients, or 62.2 percent, whose lymphoma was refractory to prior therapy. The investigators used receiver operating characteristic analysis, a statistical technique that identifies the threshold best discriminating between patients who experience events such as progression or death and those who do not, to determine optimal cutoff values for the two ratios. This analysis yielded a cutoff of 3.0 for the neutrophil-to-lymphocyte ratio and 282.0 for the platelet-to-lymphocyte ratio.

The survival analysis told a striking story. Patients whose blood counts showed an elevated neutrophil-to-lymphocyte ratio or an elevated platelet-to-lymphocyte ratio before or at the start of salvage therapy experienced significantly inferior three-year progression-free survival and overall survival compared with patients below the thresholds. But when the researchers moved from simple comparisons to multivariable Cox regression, a method that adjusts for the influence of multiple factors simultaneously, the two biomarkers diverged. The platelet-to-lymphocyte ratio held its ground: patients with a ratio of 282.0 or higher had a 2.027-fold higher hazard of progression or death, with a 95 percent confidence interval of 1.213 to 3.389 and a P value of 0.007, and a 3.874-fold higher hazard of death, with a confidence interval of 1.434 to 10.464 and a P value of 0.008. The neutrophil-to-lymphocyte ratio, by contrast, lost its statistical significance once other variables were accounted for, suggesting that the platelet arm of the inflammatory signature carries the prognostic weight in this disease and treatment context.

Recognizing that single-center retrospective findings are vulnerable to bias, the team sought external validation in an independent cohort of 64 patients drawn from two additional centers. The result reinforced the primary finding: a platelet-to-lymphocyte ratio of 282.0 or above remained significantly associated with lower three-year progression-free survival and overall survival in the validation set. This kind of replication across institutions is a critical step for any candidate biomarker, because it argues against the possibility that the signal is an artifact of local treatment patterns, laboratory calibration, or patient selection peculiar to one hospital.

The researchers then turned to one of the most clinically consequential questions in this field: what happens to patients who proceed to autologous stem cell transplantation, the standard curative-intent consolidation for eligible patients with chemosensitive relapsed disease. Pooling 60 transplantation patients from both cohorts, the team found that an elevated platelet-to-lymphocyte ratio was associated with markedly inferior outcomes even in this subgroup. Three-year progression-free survival was 46.2 percent among patients with a high ratio compared with 82.1 percent among those with a low ratio, a difference that reached statistical significance with a P value of 0.012. Overall survival showed an even starker gap, at 75.0 percent versus 97.8 percent, with a P value of 0.004. In other words, the biomarker appeared to identify, before transplantation, which patients were most likely to relapse or die despite undergoing an intensive and resource-heavy procedure.

The biology behind this association is a matter of active investigation, but several mechanisms offer plausible explanations. Platelets are far more than passive clotting agents; they release a cargo of pro-angiogenic and immunosuppressive factors, including transforming growth factor beta, and can shield circulating tumor cells from immune surveillance by coating them with platelet-derived molecules that mask recognition by cytotoxic T cells. Platelets can also promote the formation of tumor cell aggregates that facilitate dissemination. Meanwhile, relative lymphopenia may reflect a depleted or exhausted antitumor immune compartment, precisely the arm of the immune system that PD-1 inhibitors are designed to reinvigorate. A high platelet-to-lymphocyte ratio may therefore encapsulate a double disadvantage: an abundance of tumor-supporting platelet activity coupled with a weakened lymphocyte pool, leaving the patient less able to mount the immune response on which checkpoint blockade depends.

The practical appeal of the finding lies in its accessibility. Unlike genomic assays, PET imaging metrics, or circulating tumor DNA measurements, the platelet-to-lymphocyte ratio requires nothing more than a complete blood count, an investigation performed routinely in every oncology clinic worldwide, and a simple division. If prospective studies confirm the result, the ratio could be incorporated into risk-adapted algorithms for relapsed or refractory Hodgkin lymphoma, potentially guiding decisions about the timing of transplantation, the intensity of salvage chemotherapy, the addition of antibody-drug conjugates such as brentuximab vedotin, or enrollment into clinical trials of novel agents. Patients identified as high risk by this inexpensive measure could be considered for closer surveillance or earlier escalation, while those with favorable ratios might be spared unnecessary intensification.

The authors are careful to frame the work as a step toward, not a substitute for, clinical implementation. Because the study was retrospective, the possibility of unmeasured confounding cannot be excluded, and the cutoff of 282.0 was derived from the same data in which it was tested in the primary cohort, a practice that can inflate apparent performance. The researchers explicitly call for prospective validation to confirm the prognostic value of the platelet-to-lymphocyte ratio and to clarify its potential contribution to risk stratification in patients receiving PD-1-based salvage therapy. The study was approved by the Ethics Committee of Sun Yat-sen University Cancer Center and conducted in accordance with the Declaration of Helsinki, with informed consent waived for the anonymized retrospective data. Supported by the National Natural Science Foundation of China and the Science and Technology Program of Guangzhou, the work adds to a growing body of evidence that the humble blood count, interpreted through the lens of systemic inflammation, still has much to teach oncologists about the fate of patients facing one of lymphoma’s most challenging scenarios.

Subject of Research: Prognostic value of the platelet-to-lymphocyte ratio in relapsed or refractory classic Hodgkin lymphoma treated with PD-1-based salvage therapy

Article Title: Platelet-to-lymphocyte ratio as a prognostic biomarker in relapsed or refractory classic Hodgkin lymphoma treated with PD-1-based salvage therapy

Article References: Luo, G., Xitian, C., Li, Y., Jiang, H., Liu, S., Wu, C., Li, X., Zhang, C., Zheng, X., Wang, Z., Zhang, X., & Xia, W. (2026). Platelet-to-lymphocyte ratio as a prognostic biomarker in relapsed or refractory classic Hodgkin lymphoma treated with PD-1-based salvage therapy. BMC Cancer. https://doi.org/10.1186/s12885-026-16980-6

Image Credits: AI Generated

DOI: 10.1186/s12885-026-16980-6

Keywords: Hodgkin lymphoma, platelet-to-lymphocyte ratio, PD-1 inhibitors, salvage therapy, prognostic biomarker, progression-free survival, overall survival, autologous stem cell transplantation, immune checkpoint inhibitors, inflammation-based biomarkers, retrospective study, risk stratification