# Peripheral Lymphocyte Dynamics in the Immune Microenvironment of Multiple Myeloma During Autologous Stem Cell Transplantation

**Authors:** Carlos Agustin Villegas-Valverde, Imilla Casado-Hernandez, Francisco Sotomayor-Lugo, Yandy M Castillo-Aleman, Fatma Abdou, Shadi Sharif-Shamat, Antonio A Bencomo-Hernandez, Yendry Ventura-Carmenate

PMC · DOI: 10.7759/cureus.102862 · 2026-02-02

## TL;DR

This study tracks changes in immune cells in multiple myeloma patients before and after stem cell transplants, aiming to identify potential biomarkers for treatment outcomes.

## Contribution

The study provides descriptive longitudinal benchmarks for peripheral lymphocyte immunophenotypes in MM patients undergoing ASCT.

## Key findings

- Markedly low baseline B cell counts were observed in MM patients.
- A significant post-transplant decrease in helper T cells, B cells, and the CD4/CD8 ratio was observed.
- Infused lymphocyte doses were below published thresholds, but major subsets exceeded recommended cutoffs.

## Abstract

Background and objective

Autologous stem-cell transplantation (ASCT) remains the standard of care for multiple myeloma (MM), yet it is not curative. Over the past decade, there has been growing interest in immunotherapy-based strategies, highlighting the need for predictive biomarkers to tailor post-ASCT treatment. Characterization of immune status via peripheral lymphocyte immunophenotyping is a critical step in this process. This study aimed to characterize peripheral blood lymphocyte immunophenotypes in MM patients undergoing ASCT at baseline, during stem cell mobilization, and on day +21 post-transplant, and to establish descriptive longitudinal benchmarks that may inform immune monitoring in this clinical setting.

Methods

We conducted a prospective, single-center study at the Abu Dhabi Stem Cells Center (Abu Dhabi, United Arab Emirates (UAE), enrolling all MM patients undergoing ASCT between July 2020 and February 2024 (n = 28), with no additional exclusion criteria. Peripheral blood samples were collected at three time points: before ASCT, on day +21 post-ASCT, and from the apheresis product. Canonical lymphocyte markers were analyzed by flow cytometry using a single, polychromatic 10-color antibody panel on a Navios EX cytometer.

Results

Of the 28 MM patients studied, 40.3% were women. The age range was 23 to 64 years. Markedly low baseline B cell counts were observed (6-175 cells/µL). A significant post-transplant decrease in helper T cells, B cells, and the CD4/CD8 ratio was observed at day +21 compared with baseline. The mean total lymphocyte dose infused (0.20 × 10⁹ cells/kg) was below published thresholds; however, the major lymphocyte subsets exceeded recommended cutoff values, suggesting a potentially favorable prognosis. Dose ranges for non-conventional lymphocyte subsets were also determined

Conclusions

T helper and B cells declined during the peri-transplant period in patients with MM who underwent ASCT, suggesting a lack of association with the autograft dose of homologous populations. This study provides preliminary, descriptive benchmarks for minority immune cell populations, supporting their potential relevance as prognostic biomarkers.

## Linked entities

- **Diseases:** multiple myeloma (MONDO:0009693)

## Full-text entities

- **Genes:** CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, KIR2DL4 (killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 4) [NCBI Gene 3805] {aka CD158D, G9P, KIR-103AS, KIR-2DL4, KIR103, KIR103AS}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, KLRK1 (killer cell lectin like receptor K1) [NCBI Gene 22914] {aka CD314, D12S2489E, KLR, NKG2-D, NKG2D}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, CXADRP1 (CXADR pseudogene 1) [NCBI Gene 653108] {aka CAR, CXADRP}, NT5C (5', 3'-nucleotidase, cytosolic) [NCBI Gene 30833] {aka DNT, DNT1, HEL74, P5N2, PN-I, PN-II}, CD34 (CD34 molecule) [NCBI Gene 947], FASLG (Fas ligand) [NCBI Gene 356] {aka ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, PTPRC (protein tyrosine phosphatase receptor type C) [NCBI Gene 5788] {aka B220, CD45, CD45R, GP180, IMD105, L-CA}, NCAM1 (neural cell adhesion molecule 1) [NCBI Gene 4684] {aka CD56, MSK39, NCAM}, DPT (dermatopontin) [NCBI Gene 1805] {aka TRAMP}
- **Diseases:** renal dysfunction (MESH:D007674), ALC (MESH:D009845), non-Hodgkin lymphoma (MESH:D008228), multiple sclerosis (MESH:D009103), human immunodeficiency virus infection (MESH:D015658), immune dysregulation (OMIM:614878), Infectious Diseases (MESH:D003141), anemia (MESH:D000740), leukemic (MESH:D007938), Mortality (MESH:D003643), immunodeficiency (MESH:D007153), end-organ damage (MESH:C564816), cytotoxic (MESH:D064420), hypercalcemia (MESH:D006934), lytic bone lesions (MESH:D001847), B cell lymphopenia (MESH:D015448), hematologic malignancies (MESH:D019337), AML (MESH:D015470), Cancer (MESH:D009369), Morbidity (OMIM:614963), MM (MESH:D009101), GvHD (MESH:D006086)
- **Chemicals:** DNTs (MESH:C023514), Alexa Fluor 700 (-), glycolipids (MESH:D006017), Tc (MESH:D013667), FITC (MESH:D016650), Alexa Fluor 750 (MESH:C502599)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961165/full.md

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Source: https://tomesphere.com/paper/PMC12961165