Limited · humanPreprint
This prospective cohort study investigated whether adjunctive thymosin alpha 1 (Thα1) combined with intravenous immunoglobulin (IVIG), initiated 8–10 days after rituximab, could reduce pulmonary adverse events (PAEs) in 379 patients with B-cell lymphoma (BCL) receiving R-CHOP chemotherapy. Patients were assigned to either standard R-CHOP alone (n=164) or R-CHOP plus Thα1-IVIG (n=215); the study was conducted over approximately 11 years. The study found that the Thα1-IVIG group had a notably lower rate of overall PAEs (13.0% vs. 31.7%), with reductions in both infectious pulmonary events and interstitial pulmonary disease. Five-year event-free survival also appeared to favor the adjunctive group. Multivariable Cox proportional hazards models were used to identify independent risk and protective factors. Key limitations include the non-randomized, observational design (patients were not randomly assigned), potential for selection bias and confounding, the preprint status of the manuscript (not yet peer-reviewed), the single-study nature of the findings, and the lack of blinding. These factors substantially limit causal interpretation of the results, and findings should be considered hypothesis-generating pending confirmatory randomized controlled trials.
Unknown journal · Apr 2026DOI ↗ Limited · human
This case report describes a nasopharyngeal carcinoma patient who developed severe multisystem immune-related adverse events (irAEs) following combination treatment with sintilimab (a PD-1 immune checkpoint inhibitor) and thymosin alpha-1 (Tα1), an immunomodulatory peptide. The patient reportedly experienced high fever, skin rash, interstitial pulmonary edema, and multiple organ failure. The authors trace the clinical course from symptom onset through regression and use this case to discuss the potential risks of combining immune checkpoint inhibitors (ICIs) with immunomodulatory agents, suggesting that such combinations may trigger immune overactivation beyond what either agent causes alone. The paper reviews relevant literature to contextualize the case and proposes management strategies for clinicians encountering similar presentations. Key limitations include the inherent constraints of single-patient case reports: causality cannot be firmly established, findings are not generalizable, and confounding factors (e.g., underlying disease burden, other medications) cannot be fully excluded. The authors emphasize the need for heightened clinical vigilance when combining ICIs with immunomodulators like Tα1.
Clinical case reports · Feb 2026DOI ↗ Limited · human
This retrospective, single-arm study evaluated the effects of a 7-day loading dose of thymosin α1 (Tα1) on peripheral blood lymphocyte counts, as well as the safety and efficacy of combining Tα1 with hypofractionated radiotherapy and PD-1 inhibitors in 48 patients with advanced or refractory cancers. Peripheral blood T cells, B cells, and natural killer cells were measured by flow cytometry before and after Tα1 administration. The study found that the 7-day Tα1 course was associated with statistically significant increases in total T cells, CD4+ T cells, and CD8+ T cells. Secondary outcomes including objective response rate, disease control rate, progression-free survival, and overall survival were also reported alongside adverse event data, with the authors characterizing the safety and efficacy profiles as satisfactory. Key limitations include the retrospective, non-randomized, single-arm design; the small and heterogeneous patient population spanning multiple tumor types; a median follow-up of only 13.7 months, which may be insufficient to assess long-term survival and late toxicities; and the absence of a control group, making it difficult to isolate Tα1's contribution. The authors acknowledge these findings are exploratory and call for larger, randomized, homogenous cohort studies to validate results.
Cancer management and research · Nov 2025DOI ↗ Limited · human
This small open-label proof-of-concept study investigated whether thymosin alpha-1 (Tα1), a thymic peptide hormone, might reduce depressive symptoms in five patients with common variable immunodeficiency (CVID) who also had a comorbid depressive episode. The rationale was that CVID patients share immune abnormalities with major depressive disorder (MDD) patients — notably reduced naïve T cells and premature T-cell senescence — and that Tα1 can stimulate thymic output of naïve T cells, potentially improving mood via immune-limbic system pathways. Patients received Tα1 subcutaneously over eight weeks and were assessed using the Hamilton Depression Rating Scale (HDRS) alongside immune biomarkers. All five CVID patients showed reductions in HDRS scores (average 52%), compared to a 36% average reduction in a non-randomized contrast group of 42 MDD patients receiving treatment as usual. Naïve/memory T-cell ratios improved in all five patients, and IL-6 levels decreased in four of the five. However, depressive and immune improvements were not sustained in a subsequent eight-week wash-out period for the more severely affected patients. Key limitations include the very small sample size (n=5), lack of a placebo control, open-label design, and use of a non-matched contrast group. The authors conclude that larger placebo-controlled trials are warranted.
Brain, behavior, & immunity - health · Jan 2025DOI ↗ Limited · human
This prospective, open-label, randomized pilot trial (NCT04487444) evaluated the preliminary efficacy and safety of thymalfasin (synthetic Thymosin-α-1, or Tα1) compared with standard of care in 49 hospitalized COVID-19 patients presenting with both hypoxemia and lymphocytopenia. The primary clinical outcome—rate of clinical recovery—was numerically higher in treated patients receiving either low-flow or high-flow baseline oxygen support, but neither difference reached statistical significance (subdistribution hazard ratios of 1.48 and 1.28, respectively, with wide confidence intervals crossing 1.0). A notable immunological finding was that treated patients on baseline low-flow oxygen had, on average, 3.84 times more CD4+ T cells on day 5 compared with day 1, versus controls (P = .01), suggesting faster T-cell reconstitution. Nine serious adverse events occurred in the treatment group but were adjudicated as unrelated to Tα1. Key limitations include the small sample size (n=49), open-label design (no blinding), and lack of statistical power to draw definitive efficacy conclusions. The authors suggest Tα1 may have a role in managing COVID-19-related immunosuppression, but larger trials are needed to confirm these preliminary findings.
The Journal of infectious diseases · Jan 2023DOI ↗