Blood levels of immune cells predict survival in myeloma patients: results of an Eastern Cooperative Oncology Group phase 3 trial for newly diagnosed multiple myeloma patients

Abstract

Previously, it was reported that patients with multiple myeloma (MM) who have higher baseline levels of blood CD4 ؉ or CD19 ؉ cells have longer survival. This article extends the analysis of immune cell levels and survival in a large cohort (N ‫؍‬ 504) of patients with MM entered on Eastern Cooperative Oncology Group (ECOG) phase 3 trial (9486). Newly diagnosed patients with MM received 2 cycles of vincristine, bischloroethylnitrosourea, melphalan, cytoxan, prednisone (VBMCP) and were treated on one of 3 randomized arms: VBMCP with either interferon or high-dose cyclophosphamide, or VBMCP alone. Blood immune cell levels were studied at trial entry (baseline), after 2 cycles of chemotherapy, after 2 years of therapy, and at relapse. Baseline CD3 ؉ , CD4 ؉ , CD8 ؉ , CD19 ؉ , and CD4 ؉ subset cell levels were all positively associated with survival (P ‫؍‬ .0087 to P < .0001). A multivariate analysis incorporating CD4 ؉ and CD19 ؉ cell levels defined 3 separate groups of patients with MM to survival outcome. Higher CD19 ؉ blood levels were positively associated with MM-patient survival at entry to the study, at year 2, and at relapse (P < .0001 at all 3 timepoints). Patients with MM had evidence of immune cell reconstitution after 2 years of therapy, but the rate and extent of recovery was greater for CD8 ؉ , which was greater than CD4 ؉ , which was greater than CD19 ؉ . This latter data affirms the positive relationship between the quantitative status of the blood immune system in MM and survival. In addition, the importance of the CD19 ؉ blood cells to survival is evident throughout the course of MM. Therapeutic efforts to maintain an intact immune system may be crucial in maximizing chemotherapeutic and/or immunotherapy efforts in this disease. (Blood. 2001;98:23-28)

Prognostic analysis of pre-transplant peripheral T-cell levels in patients receiving an autologous hematopoietic progenitor-cell transplant

“…29 Additionally, CD4 T-cell counts associate with survival in patients with multiple myeloma treated on an Eastern Cooperative Oncology Group phase III trial comparing three different nontransplant approaches. 30 These observations, combined with the results of the present study, suggest the existence of a tumor-primed memory CD4 þ CD45RAÀCD62LÀ T-cell population in patients undergoing an autologous transplant, which may play a role in control of minimal residual disease after transplant. Consistent with this concept, CD4 þ CD45RAÀCD62LÀ memory T cells are known for their ability to mediate cell-mediated immunity.…”

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

“…immune paresis), with compromised production and BM homing of normal plasma cells, is a hallmark of symptomatic MM. 11,[34][35][36] In LTDC-MM, we observed a replenishment of early B-cell subsets in the BM (B-cell precursors), translating into increased numbers of circulating immature and naïve B-cells in PB, and a recovery of end-stage normal plasma cells in the BM. Recovery of B-cell production in the BM could be related to decreased competition between clonal plasma cells and normal plasma cells (as well as B-cell precursors), for a limited number of SDF-1-associated BM niches.…”

Exercise in patients coping with breast cancer: An overview

“…The effect of treatment of cancer on immune functions and the positive effects of good immune function on survival and morbidity in cancer patients have been linked [12] . Scientific data has suggested cancer and its treatment are related with a disruption of immune functions [12,13] .…”