Effects Of Bendamustine Plus Rituximab On The Distribution Of Normal Peripheral Blood Leucocyte Populations In Advanced-Stage Chronic Lymphocytic Leukemia (CLL)

Autor: Marcos González, Javier Loscertales, Jose Antonio Garcia Marco, Julia Almeida, Susana Barrena, Javier de la Serna, Pilar Rabasa, Teresa Olave, Alberto Orfao, Jose Francisco Tomas, Rosa Ana Rivas, Martin Perez-Andres, Fernando Solano, Georgiana Grigore, Mª José Allegue, Inmaculada Pérez, Angeles Medina
Rok vydání: 2013
Předmět:
Zdroj: Blood. 122:5289-5289
ISSN: 1528-0020
0006-4971
DOI: 10.1182/blood.v122.21.5289.5289
Popis: Introduction Management of B-cell chronic lymphocytic leukemia (CLL) is currently undergoing profound changes. Accordingly, new treatment options with an expected less toxicity than standard regimens are been explored. Recent results show that chemoimmunotherapy may improve the life expectancy of CLLpatients and has proven to be more efficient than chemotherapy alone in depleting malignant cells. Despite its efficacy, little is known about its precise immunomodulatory effects. Aim To evaluate the effects of chemoimmunotherapy with bendamustine plusrituximab (BR) on the distribution of normal residual leucocyte populations in peripheral blood (PB) from advanced-stage CLL patients, with special emphasis on maturation-associated B-cell subsets (immature, naïve, memory IgM/IgG/IgA and plasma cells). Material and Methods Distribution of PB neoplastic cells and residual normal immune cell subpopulations were analyzed in 72 CLL patients with advanced disease (Binet B/C), before therapy (M0) and after 1 course of BR (M1). The same analysis was repeated 3 months after completing treatment (M3) in 31/72 patients. PB leucocyte cell subsets were identified at each time-point by 8-color flow cytometry with monoclonal antibody reagents against CD3, CD4, CD5, CD8, TCRgd, CD19, CD20, CD27, CD38, CD45, CD56, sIgM, sIgA, sIgG, sIgLambda and sIgKappa. Results After the first BR course, absolute counts of all PB myeloid subsets were significantly decreased as compared to time M0, including neutrophils (2,744±1,830 vs 4,764±2,906 cells/uL, p In turn, total T cells were reduced in M1 as compared to M0 values (818±655 vs 3,905±2,375 cells/uL, p0.05) were observed for CD8 and TCRgd for M3 vs. M1, while CD4+ T-cell numbers were significantly reduced (p=0.006), resulting in an inverted CD4/CD8 ratio (0.9±1.0 vs. 1.8±1.3, p=0.005) at the M3 time-point. As regards B cells, the absolute count of both neoplastic and normal B lymphocytes were significantly decreased at time M1 vs. M0 (3,363±9,353 vs 53,521±56,602 CLL cells/uL and 2±6 vs 58±107 normal B-cells/uL, p=0.006 and p Conclusions All PB leucocyte subsets are affected by BR treatment in advanced-stage CLL. Interestingly, at time M3 the CD4+ T-cell subset continues to be decreased, while the other T-cell compartments seem to remain stable. Also, normal B cells are affected by BR treatment, and the depletion induced after one course therapy is maintained even three months after finishing BR therapy, except for immature B cells, that seem to be the first to recover in PB. Further studies will offer a more accurate insight into the biology of cell recovery during and after BR therapy in CLL patients. Disclosures: No relevant conflicts of interest to declare.
Databáze: OpenAIRE
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