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

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.

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.

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