Abstract
Objective: Our study aimed to analyze the measurable residual disease (MRD), complete blood count (CBC), and immune cell profiles in multiple myeloma (MM) patients treated with bortezomib /adriamycin /dexamethasone (PAD) chemotherapy sequential autologous stem cell transplantation (ASCT) to determine their prognostic value and their interaction.
Methods: CBC data from 93 MM patients were collected at diagnosis, before ASCT, and 3 months after ASCT. Immune cell profiles were detected by flow cytometry in fresh peripheral blood (PB) samples from 33 out of the 93 enrolled patients before ASCT and 3 months after ASCT. We then studied the relationship between MRD status and prognosis, the predictive value of CBC, and the changes in immune cell profiles before and after ASCT in multiple myeloma patients and their association with prognosis.
Results: Early MRD-negative patients after ASCT had significantly longer progression-free survival (PFS) (median PFS was 36 months and 25 months, respectively, P < 0.05) and overall survival (OS) (median OS was 39 months and 33 months, respectively, P < 0.05) than MRD-positive patients. Three independent prognostic factors, neutrophil count (NEU), platelet count (PLT), and lymphocyte monocyte ratio (LMR) at diagnosis, were identified in our study group by LASSO regression. For the immune cell profiles, before ASCT, the negative immunomodulatory cell subsets (CD4/CD8 double-negative T cells (DNTs), regulatory T cells (Tregs), CD16+ CD56high NK cells), PD1+ CD4+ central memory T cells (PD1+T4CM), HLA-DR+ CD8+T cells were lower in MRD-negative or disease control patients than in MRD-positive or progressive disease patients (P < 0.05). Otherwise, naive CD8+ T Cells (T8N) and CD28+ CD27+ naive CD8+T Cells (CD28+ CD27+ T8N) were higher in MRD-negative or disease control patients than in MRD-positive or progressive disease patients (P < 0.05). After ASCT, the levels of lymphocytes, marginal zone B cells, γδ T cells, and the ratio of (naive T cells plus central memory T cells to effector memory T cells plus effector T cells) were higher in disease control patients than in patients with progressive disease (P < 0.05).
Conclusion: CBC, MRD, and immune cell profile detection before and after ASCT have significant prognostic value in MM patients. Lower levels of NEU or PLT, higher levels of LMR at diagnosis, and a higher number of negative immunomodulatory cell subsets and activated T lymphocytes before ASCT were associated with poor prognosis. On the other hand, lower levels of depleted T lymphocytes, and higher levels of functional T cells and marginal zone B cells after ASCT predicted a good prognosis.