Evaluation of Plasma Cell Propidium-Iodide and Annexin-v Indices: Their Relation to Prognosis in Multiple Myeloma

Abstract

In a group of 117 patients with multiple myeloma (MM) examined at the time of diagnosis, i.e. excluding previous chemotherapy, we analysed the levels of propidium-iodide (proliferative) -PC-PI/CD 138 and annexin-V (apoptotic) -PC-AI/CD 138 indices of myeloma plasmocytes using the method of flow-cytometry to determine their relationship to prognosis. It was revealed that patients with high values of PC-PI/CD 138 had substantially worse overall survival than those with low values. Patients with a level of propidium-iodide index ≥ 2,8 % exprimed a median survival of 13 months only in comparison with 42 months in patients with levels < 2,8 % (p = 0,0005). In the PC-AI/CD 138 index a reverse trend was registered. Patients with PC-AI/CD 138 ≥ 4,0 % had long overall survival (median was not assessable at the time of evaluation), whereas patients with low apoptosis values < 4,0 % had median overall survival 16 months only (p = 0,01). Based on the sequentional graphic analysis of the curves of overall survival was found that the optimal discrimination level sequestering patients with good and poor prognosis was, in the case of PC-PI/CD 138 value 2,8 %, whereas in the case of PC-AI/CD 138 value 4,0 %. Among patients with good prognosis, there were no statistically significant differences in overall survival according to different levels of proliferative and apoptotic index. We conclude that evaluation of the propidium-iodide and annexin-V index using flow-cytometry is a quick, useful, and easily accessible method for the evaluation of plasma cell kinetics and thus prognosis of the disease, multiple myeloma.

Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms

“…Nonetheless, its independent predictive value remained valid, although it decreased, even in samples that were analyzed 24 h after extraction. This is in agreement with numerous studies in PCNs demonstrating a prognostic capacity of either the proliferation rate, [14][15][16][17][18][19] the apoptosis rate [20], or Ratio-PA [28,29]. Although, in light of our results, these studies may have underestimated the prognostic capacity of these parameters, it has been well-established that the PC proliferation rate is one of the most important independent prognostic factors, a specific marker of MM aggressiveness [31][32][33] and an early marker for disease progression and death [31,34].…”

Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell‐related disorders

“…In line with the key relevance of such PC interaction in the BM, preliminary results suggest that a higher percentage of annexin V þ PC (apoptotic index) detected ex vivo among immunomagnetically isolated CD138þ BM PC is associated with a more prolonged survival. (95)(96)(97) In the last decade, MFC immunophenotypic characterization of phenotypically aberrant PC has also been suggested to be a valuable tool for the detection of potential therapeutical targets on clonal PC and orientate tailored antibody-based therapies (and subsequent monitoring). Thus, MoAbs targeting the overall PC population (CD138) (98,99) or either growth factor receptors (IL-6 or IGF-1) (100,101) and other cell surface antigens expressed by aberrant PC (CD33, CD40, CD52, or CD74) (102)(103)(104)(105)(106)(107) and specific markers whose expression is restricted to subsets of PC (e.g.…”

Clinical Relevance of Multicolour Flow Cytometry in Plasma Cell Disorders

“…Also, the potential significance of the expression of several markers involved in the interaction between clonal PC and BM stromal cells is currently under investigation. Markers like VLA-1, ICAM-1, CD44 and Annexin-V seem promising in this regard [85][86][87][88].…”