UICC stage IV small-cell lung cancer (SCLC) is a highly aggressive malignancy without curative treatment options. Several randomized trials have demonstrated improved survival rates through the addition of checkpoint inhibitors to first-line platin-based chemotherapy. Consequently, a combination of chemo- and immunotherapy has become standard palliative treatment. However, no reliable predictive biomarkers for treatment response exist. Neither PD-L1 expression nor tumor mutational burden have proven to be effective predictive biomarkers. In this study, we compared the cellular immune statuses of SCLC patients to a healthy control cohort and investigated changes in peripheral blood B, T, and NK lymphocytes, as well as several of their respective subsets, during treatment with immunochemotherapy (ICT) using flow cytometry. Our findings revealed a significant decrease in B cells, while T cells showed a trend to increase throughout ICT. Notably, high levels of exhausted CD4+ and CD8+ cells, alongside NK subsets, increased significantly during treatment. Furthermore, we correlated decreases/increases in subsets after two cycles of ICT with survival. Specifically, a decrease in Th17 cells indicated a better overall survival. Based on these findings, we suggest conducting further investigation into Th17 cells as a potential early predictive biomarkers for response in patients receiving palliative ICT for stage IV SCLC.

Donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation (alloSCT) is an established method to enhance the Graft-versus-Leukemia (GvL) effect. However, alterations of cellular subsets in the peripheral blood of DLI recipients have not been studied. We investigated the changes in lymphocyte subpopulations in 16 patients receiving DLI after successful alloSCT. Up to three DLIs were applied in escalating doses, prophylactically for relapse prevention in high-risk disease (n = 5), preemptively for mixed chimerism and/or a molecular relapse/persistence (n = 8), or as part of treatment for hematological relapse (n = 3). We used immunophenotyping to measure the absolute numbers of CD4+, CD8+, NK, and CD56+ T cells and their respective subsets in patients’ peripheral blood one day before DLI (d-1) and compared the results at day + 1 and + 7 post DLI to the values before DLI. After the administration of 1 × 10⁶ CD3+ cells/kg body weight, we observed an overall increase in the CD8+ and CD56+ T cell counts. We determined significant changes between day − 1 compared to day + 1 and day + 7 in memory and activated CD8+ subsets and CD56+ T cells. Applying a higher dose of DLI (5 × 10⁶ CD3+ cells/kg) led to a significant increase in the overall counts and subsets of CD8+, CD4+, and NK cells. In conclusion, serial immune phenotyping in the peripheral blood of DLI recipients revealed significant changes in immune effector cells, in particular for various CD8+ T cell subtypes, indicating proliferation and differentiation.

Background/Objectives: Flow-cytometric readouts in acute myeloid leukemia (AML) may depend on specimen source and processing. We assessed whether sample source (peripheral blood [PB] vs. bone marrow [BM]) and cryopreservation influence immune-evasion-related markers on AML blasts. Methods: Paired PB and BM samples from 19 adults were analyzed fresh and after cryopreservation. Viable CD45^dim singlets were assessed for ULBP1-6, MICA/B, CD34, CD44, CD70, CD80, and CD184 using median fluorescence intensity (MFI) and relative fluorescence index (RFI). Paired comparisons used two-sided Wilcoxon signed-rank tests with Benjamini–Hochberg correction across six markers within each endpoint and comparison. Discordance was also assessed using a predefined conventional 20% reference threshold. Results: After adjustment, RFI did not differ between fresh and cryopreserved samples within PB or BM, or between fresh PB and BM. In cryopreserved samples, PB and BM differed for CD70 (q = 0.042) and ULBP1-6 (q = 0.028). Cryopreservation increased MFI for CD184 and ULBP1-6 in PB and BM and for MICA/B in PB; no PB-BM MFI difference remained significant. Threshold-based classification was discordant for CD34, CD44, CD80, CD184, MICA/B, and ULBP1-6 in 5.3–38.9% of pairs, whereas CD70 showed none. Conclusions: Cohort-level differences were limited to specific markers and conditions, while patient-level threshold discordance persisted. Sample source and cryopreservation should therefore be considered when interpreting threshold-based classifications.

Acute myeloid leukemia (AML) with translocation t(8;16)(p11;p13) represents a rare entity that has been categorized as a disease‐defining recurring cytogenetic abnormality with adverse risk in the 2022 European LeukemiaNet classification. This rating was mainly based on a retrospective analysis comprising patients from several large clinical trials, which, however, included only 21 patients treated with allogeneic stem cell transplantation (alloSCT). Therefore, the European Society for Blood and Marrow Transplantation performed a registry study on a larger cohort to evaluate the role of alloSCT in t(8;16) AML. Sixty transplant recipients with t(8;16) AML were identified. Two‐year overall and leukemia‐free survival (OS/LFS) was 43/39%. Patients transplanted in first complete remission (CR1, n = 44) achieved a 2‐year OS/LFS of 48%/48%. Following alloSCT in CR1, the multivariable analysis identified a complex karyotype (CK) as a major risk factor for relapse (HR 4.17, p = .016), lower LFS (HR 3.38, p = .01), and lower OS (HR 3.08, p = .017). Two‐year OS/LFS of patients with CK was 19%/19%, in contrast to 67%/67% in patients with t(8;16) outside a CK. Other factors for inferior outcomes were older age and secondary AML. In summary, alloSCT could mitigate the adverse risk of patients with t(8;16) AML not harboring a CK, particularly when performed in CR1.