Implementation of International Prognostic Index with flow cytometry immunophenotyping for better risk stratification of chronic lymphocytic leukemia

Abstract

Background Current chronic lymphocytic leukemia (CLL) International Prognostic Index (IPI) stratifies patients based on clinical, molecular, and biochemical features; however, B‐cell markers also influence CLL outcomes. Here, prognostic roles of CD11c, CD38, and CD49d were first evaluated, and then an immunophenotypic score was combined with CLL‐IPI for risk stratification of CLL patients. Methods A total of 171 CLL subjects were included, and surface marker expression was assessed by flow cytometry. Levels ≥30% were chosen as cut‐off of positivity to a marker; then values of 1 (for CD11c and CD38) or 3 (for CD49d) were assigned and scores determined for each patient's clone immunophenotype. Results CD49d positivity was significantly associated with simultaneous expression of CD11c and/or CD38, unmutated IGHV status, and higher β2‐microglobulin levels compared to those with CD49d negativity. Moreover, CD49d+ patients experienced a shorter progression‐free survival and time to treatment. When the immunophenotypic score was combined with CLL‐IPI, patients with high‐risk immunophenotype had a significantly lower time‐to‐treatment regardless CLL‐IPI. Conclusions Our results suggested clinical utility of an integrated prognostic score for better risk stratification of CLL patients. These results require further validation in prospective larger studies.

The role of polymorphic cytochrome P450 gene (CYP2B6) in B-chronic lymphocytic leukemia (B-CLL) incidence and outcome among Egyptian patients

“…Using flow cytometry, we discovered that the expression of (CD5, CD19, CD20, CD23, CD10, CD22, FMC7, CD38, CD49d, sIg, ƛ-light chain and ƙ-light chain) was present in (97%, 100%, 100%, 95%, 7%, 10%, 6%, 35%, 42%, 6%, 43% and 57%, respectively). Expression of CD38 and CD49d is thought to be a poor prognostic factor as they help leukemia cells migrate and homing to secondary lymphoid organs and stimulate B-CLL cell proliferation in tandem with BCR signaling [ 32 ].…”

Commentary: Flow cytometry quantification of tumor-infiltrating lymphocytes to predict the survival of patients with diffuse large B-cell lymphoma

“…Moreover, as new techniques such as phosphoflow cytometry have been applied in clinical studies (15)(16)(17), flow cytometry-based prediction models can be substantially improved in the future. Markers of tumor and TME interaction can also be integrated into the standard prognostic scoring systems as proposed in chronic lymphocytic leukemia (18).…”